Life. Death. Immortality.: The Reign of the Genome 3031275519, 9783031275517

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T H E

F R O N T I E R S

C O L L E C T I O N

Gennadiy Zhegunov Denys Pogozhykh

LIFE . DE ATH. I M MORTA LIT Y. The Reign of the Genome

123

The Frontiers Collection Series Editors Avshalom C. Elitzur, Iyar, Israel Institute of Advanced Research, Rehovot, Israel Zeeya Merali, Foundational Questions Institute, Decatur, GA, USA Maximilian Schlosshauer, Department of Physics, University of Portland, Portland, OR, USA Mark P. Silverman, Department of Physics, Trinity College, Hartford, CT, USA Jack A. Tuszynski, Department of Physics, University of Alberta, Edmonton, AB, Canada Rüdiger Vaas, Redaktion Astronomie, Physik, bild der wissenschaft, Leinfelden-Echterdingen, Germany

The books in this collection are devoted to challenging and open problems at the forefront of modern science and scholarship, including related philosophical debates. In contrast to typical research monographs, however, they strive to present their topics in a manner accessible also to scientifically literate non-specialists wishing to gain insight into the deeper implications and fascinating questions involved. Taken as a whole, the series reflects the need for a fundamental and interdisciplinary approach to modern science and research. Furthermore, it is intended to encourage active academics in all fields to ponder over important and perhaps controversial issues beyond their own speciality. Extending from quantum physics and relativity to entropy, consciousness, language and complex systems—the Frontiers Collection will inspire readers to push back the frontiers of their own knowledge.

Gennadiy Zhegunov · Denys Pogozhykh

Life. Death. Immortality. The Reign of the Genome

Gennadiy Zhegunov State Biotechnology University Kharkiv, Ukraine

Denys Pogozhykh Hannover Medical School Hannover, Germany

ISSN 1612-3018 ISSN 2197-6619 (electronic) The Frontiers Collection ISBN 978-3-031-27551-7 ISBN 978-3-031-27552-4 (eBook) https://doi.org/10.1007/978-3-031-27552-4 © Springer Nature Switzerland AG 2023 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Reality is a special case of the possible

Preface

The present book has been written on the basis of scientific views, but it contains many new hypotheses, original reasoning, philosophizing, and unconventional views of established scientific dogmas. This is a scientific and philosophical book that seeks to generalize and understand seemingly incompatible concepts, using a philosophical approach. Life is a very widespread phenomenon on our planet. It can be characterized by many fundamental features that distinguish living entities from non-living ones. It is clear that life is a qualitatively special form of the existence of matter; however, as the manifestations of life are extremely complex and diverse, we don’t yet have a complete and clear understanding of this phenomenon. Here, we shall analyze this mysterious phenomenon from a new perspective. Although the book’s material is based on classical concepts of life, we shall view this biological phenomenon from a non-standard point of view. In order to understand the essence of such a complex phenomenon, we proceeded from the fact that, on the one hand, life is associated with the process of existence of living bodies with certain physical characteristics and with a short individual life, while on the other hand, life is a natural phenomenon, a permanent unified planetary system of life, which is one of the properties of the material world. In other words, life as a global phenomenon of nature should be distinguished from the phenomenon of existence of living bodies, despite their inseparable relation. We consider the genome not only in its conventional meaning as a set of genetic material and information, but also as a comprehensive integrated system. It is a structure capable of manipulating substances and information, self-reproducing, and building a phenotypic framework (phenome) in the form of a living body around itself. Thus, we develop the hypothesis of the primacy and predominant role of the genome in relation to the cells and living bodies in which it “lives”. The totality of genomic information of all living organisms on Earth, based on nucleic acids, forms a vast information system of life (genosphere), and on this basis, a vast heterogeneous system of living bodies (phenosphere) of a singular proteinic nature is formed. Life can thus be considered as a peculiar form of coexistence of matter and information.

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Preface

The sudden occurrence and inevitable death of living bodies are considered as the most important characteristics that distinguish the living from the inanimate. Genomes migrate with reproduction from one body to another, remaining virtually unaltered. Hence, we can speak of the mortality of living bodies, but immortality of genomes and the biological information contained in them. This determines the permanent essence of the phenomenon of life. Therefore, the planetary system of life can be considered virtually eternal, existing for billions of years against the background of the fleetingness of individual life. Kharkiv, Ukraine Hannover, Germany

Gennadiy Zhegunov Denys Pogozhykh

Acknowledgments The authors would like to express special thanks to Prof. Dr. Oleg Nardid and Prof. Dr. Marina Petrushko for fruitful discussions and valuable comments on the manuscript, as well as Dr. Igor Kovalenko for producing many of the drawings in this book.

About This Book

What are life and death? Is it possible to understand their essence and give clear definitions? Countless books and articles have been devoted to trying to answer these intriguing questions. However, there are still no definite and generally accepted answers. The intrigue remains. And meanwhile, human attempts to vanquish death and achieve immortality continue apace. This book is an attempt to answer the eternal questions about life and death by analyzing, synthesizing, and rethinking the known facts that characterize life. The material here should be of particular interest, as it contains many hypotheses, philosophical generalizations, and well-informed speculations. What is most important for life—matter, energy, or information? How are individual lives and the phenomenon of life in general related? What serves what—does the genome serve the cell or does the cell serve the genome? What is the value of life and death? Can we become immortal? The inquisitive reader will find answers to these and other exciting questions in the pages of this original book.

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Contents

Part I 1

Phenomenon of Life

Basics 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 1.10 1.11 1.12 1.13 1.14

1.15 1.16 Part II 2

........................................................ The Ambiguity of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Main Feature of the Earth . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Material Backbone of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Energy Backbone of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Nucleic Acid Backbone of Life . . . . . . . . . . . . . . . . . . . . . . . . The Protein Backbone of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Aqueous Backbone of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . The Thermodynamic Backbone of Life . . . . . . . . . . . . . . . . . . . . . The Catalytic Backbone of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . The Systemic Backbone of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . Compartmentalization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Informational Backbone of Life . . . . . . . . . . . . . . . . . . . . . . . Cellular Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Non-cellular Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.14.1 Viruses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.14.2 Cellular-Viral System of Life . . . . . . . . . . . . . . . . . . . . . . 1.14.3 Molecular-Genetic Communication . . . . . . . . . . . . . . . . 1.14.4 Are Viruses Living Organisms? . . . . . . . . . . . . . . . . . . . . Hidden Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3 3 5 10 13 16 19 21 26 29 30 33 35 39 43 43 45 46 48 49 53

Planetary System of Life

The Unified System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Living Bodies Are the Organizers of the Planetary System of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 All Life Comes from Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Levels of Organization of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . .

57 57 60 61

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2.4 2.5 2.6 2.7

Self-organization and Emergent Properties of Living Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Illusion of Diversity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Genomes, Phenomes, and the Planetary System of Life . . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

64 70 75 81

Part III Living Bodies. Individual Life 3

Eukaryotic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 3.1 The Main Characteristics of Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 85 3.2 The Main Body Parts of Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 3.2.1 Nucleus—The Site of the Genome . . . . . . . . . . . . . . . . . 88 3.2.2 Cytoplasm—The Site of the Phenome . . . . . . . . . . . . . . 91 3.2.3 Surface Apparatus and Biological Membranes . . . . . . . 97 3.3 Cellular Nanoconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 3.4 Cells and Their Fragments in Vitro . . . . . . . . . . . . . . . . . . . . . . . . 100 3.5 Why is the Cell Needed? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 3.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

4

Multicellular Organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Cells and Multicellular Organisms . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 A Living Organism is the Phenotypic Framework of Its Genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

105 105

General Characteristics of Living Bodies . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Principles of Organization of Living Bodies . . . . . . . . . . . . . . . . . 5.2 Motion and Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 Biological Expediency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4 Biological Versatility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5 Fractality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6 Bioautonomy as the Basis for Independent Existence . . . . . . . . . 5.6.1 Self-Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6.2 Self-Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6.3 Self-Preservation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6.4 Self-Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6.5 Self-Sufficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6.6 Self-Reproduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6.7 Self-Construction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6.8 Homeostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

111 111 114 118 120 123 125 125 126 127 128 129 129 130 130 131

5

107 109

Part IV The Nature of Vitality in Living Bodies 6

Basic Properties and Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 6.1 Nutrition and Digestion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 6.2 Water Consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

Contents

6.3 6.4 6.5 6.6 6.7 7

Respiration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Motion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reproduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

138 139 141 143 143

Basic Processes and Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1 Bodies, Processes, Mechanisms, Interactions, States, and Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 Enzyme Catalysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3 Transformation of Substances and Energy . . . . . . . . . . . . . . . . . . 7.4 Thermodynamic Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.5 Electrostatic and Electrodynamic Mechanisms . . . . . . . . . . . . . . . 7.6 Quantum Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.7 Informational-Genetic Processes and Mechanisms . . . . . . . . . . . 7.8 Cytological and Cytogenetic Macroprocesses and Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.9 Intracellular Functional Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.10 Functional Associations of Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.11 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

145

Part V 8

xiii

145 149 156 162 166 170 173 175 178 180 183

Genesis and Evolution

Genesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.1 The Probability of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2 The Main Stages of Phylogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2.1 Emergence of the Pattern of Organization of Living Bodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2.2 Emergence of Living Bodies and Individual Life . . . . . 8.2.3 Emergence of the Planetary System of Life . . . . . . . . . . 8.2.4 The Emergence of Death and Immortality . . . . . . . . . . . 8.3 The Role of Temperature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4 Properties of Genomes and Evolution . . . . . . . . . . . . . . . . . . . . . . 8.4.1 Heredity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.2 Variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.3 Natural Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.4 Evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.5 Co-evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.6 Symbiogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.7 Gene Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.8 Bioinfogenesis and Infobiogenesis . . . . . . . . . . . . . . . . . 8.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

187 187 190 190 192 197 198 200 203 203 205 209 211 216 216 218 221 223

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Contents

Part VI 9

Reproduction and Development

Self-reproduction of Genomes and Living Bodies . . . . . . . . . . . . . . . . . 9.1 The Purpose of Reproduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2 Types of Reproduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.1 Asexual Reproduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.2 Sexual Reproduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.3 Gametes as a Transitory Form of Genomes . . . . . . . . . . 9.2.4 Gametogenesis is the Process of Transformation of Genomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.5 Fertilization as Integration of Genomes . . . . . . . . . . . . . 9.2.6 The Zygote as the Beginning of a New Life for Genomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.3 Division of Cells and Their Genomes . . . . . . . . . . . . . . . . . . . . . . 9.3.1 Interphase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.3.2 Mitosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.3.3 Chromosomal Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4 Meiosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.5 The Role of the Genome in Reproduction . . . . . . . . . . . . . . . . . . . 9.6 Transit of Genomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.7 Exchange of Living Bodies (and Genomes) . . . . . . . . . . . . . . . . . 9.8 Reproduction as a Means of Survival for Genomes . . . . . . . . . . . 9.9 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

227 227 229 229 230 233

10 Development or Self-construction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.1 Genesis and Individual Development . . . . . . . . . . . . . . . . . . . . . . . 10.2 Growth and Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.3 Development Mechanisms in Complex Organisms . . . . . . . . . . . 10.4 Differentiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

261 261 265 267 269 273

Part VII

235 237 237 239 240 244 246 247 251 255 256 257 259

The Inevitability of Death and the Mechanisms of Survival

11 Life Expectancy, Aging, and Death of Living Bodies . . . . . . . . . . . . . . 11.1 Life Expectancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2 Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3 Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3.1 Death of Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3.2 Death of Multicellular Organisms . . . . . . . . . . . . . . . . . . 11.4 The Ambiguity of Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.5 Phenotypic Death and Genotypic Immortality . . . . . . . . . . . . . . . 11.6 The Illusion of Death and the Illusion of Life . . . . . . . . . . . . . . . . 11.7 The Value and the Price of Individual Life and Death . . . . . . . . . 11.8 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

277 278 285 293 295 298 301 303 305 305 306

Contents

12 Survival Pathways for Living Bodies and Their Genomes . . . . . . . . . 12.1 Maintaining Integrity and Homeostasis: Self-repair . . . . . . . . . . . 12.2 Reproduction of Genomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.3 Adaptation and Evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.4 Hypobiosis and Anabiosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.5 The Purpose of the Lives of Individuals . . . . . . . . . . . . . . . . . . . . 12.6 The Strategy of Monolithic Coexistence . . . . . . . . . . . . . . . . . . . . 12.7 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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309 309 312 313 316 318 319 320

Part VIII Power of the Genome 13 Cognitiveness of Living Bodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.1 Information and Control Principles . . . . . . . . . . . . . . . . . . . . . . . . 13.2 Informativeness of Matter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3 Biothesaurus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.4 Entropy and Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.5 Information and Levels of Development . . . . . . . . . . . . . . . . . . . . 13.6 Living Computers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.7 Genetic Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.7.1 Basics of Organization and Application . . . . . . . . . . . . . 13.7.2 Simultaneous Transformations of Matter and Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.7.3 Carriers and Information . . . . . . . . . . . . . . . . . . . . . . . . . . 13.7.4 Properties and Characteristics of Genetic Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.8 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

323 323 328 329 331 333 334 339 339

14 Materials, Devices, and Mechanisms of the Genome . . . . . . . . . . . . . . 14.1 Genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.1.1 Repository of Information . . . . . . . . . . . . . . . . . . . . . . . . 14.1.2 Structural and Functional System . . . . . . . . . . . . . . . . . . 14.2 Stem Molecules of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.3 Genetic Material . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.3.1 Chromatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.3.2 Chromosomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.3.3 Karyotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.4 Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.5 Genetic Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.6 Expression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.7 Template Processes. Copying and Cloning . . . . . . . . . . . . . . . . . . 14.8 Functional Systems of Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.9 Directed Genome Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . 14.10 Transgenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.11 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

347 347 347 348 352 354 354 355 358 360 362 366 370 371 375 379 381

340 341 342 344

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Contents

Part IX The Dual Nature of the Phenomenon of Life 15 Living Bodies and the Planetary System . . . . . . . . . . . . . . . . . . . . . . . . . 15.1 The Duality of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.2 The Nature of Living Bodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.3 The Nature of the Planetary System and the Phenomenon of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

385 385 386 389

16 Matter and Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393 17 Genomes and Their Bodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.1 The Cell is for the Genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.2 Dual Unity of Genome and Phenome . . . . . . . . . . . . . . . . . . . . . . . 17.3 Species of Genomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.4 Global Phenome and Global Genome . . . . . . . . . . . . . . . . . . . . . . 17.5 Phenotypic and Genotypic Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Part X

395 395 397 398 402 403 405

Immortality

18 Information Constancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18.1 Time, Space, and Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18.2 The Emergence and Death of Organisms . . . . . . . . . . . . . . . . . . . . 18.3 Genomic Cycles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18.4 Info-Genetic Continuity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

409 409 411 414 415

19 Conclusion: Dictatorship of the Genome . . . . . . . . . . . . . . . . . . . . . . . . . 423 Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431

Part I

Phenomenon of Life

Chapter 1

Basics

1.1 The Ambiguity of Life Hundreds of definitions of “life” have been proposed by scientists and philosophers over hundreds of years of reflection. Some differ fundamentally and often contradict each other, but on the whole they are complementary. As examples, we will give only a few definitions based on the points of view of scientists from different fields. More than 100 years ago, the philosopher Friedrich Engels defined life as follows: “Life is the mode of existence of protein bodies, the essential element of which consists in continual metabolic interchange with the natural environment outside them, and which ceases with the cessation of this metabolism, bringing about the decomposition of the protein”. This definition is still one of the most popular, despite subsequent advances in science. Here, the dominant role of proteins and the necessity of metabolism are specified for the first time. Physicist Mikhail Volkenshtein, in the middle of the last century, gave a fundamentally new definition: “Living bodies that exist on Earth are open, self-regulating and self-reproducing systems built of biopolymers: proteins and nucleic acids.” This definition relates rather to living bodies (organisms) than to the phenomenon of life. Yet, it contains the concept of a “system” and two highly important new parameters: self-reproduction and nucleic acids. In 1944, Erwin Schrödinger wrote his book “What Is Life? The Physical Aspect of the Living Cell”. This book discusses the thermodynamic, informational, and quantum basics of life. Chemist Valentin Parmon defines life as a phase-isolated form of existence of functioning autocatalysts, capable of chemical mutations and having undergone a fairly long evolution by natural selection. This definition emphasizes the most important characteristics of life: catalysis and evolution. Physical chemist Ilya Prigogine established the decisive role of self-organization in the nonequilibrium systems that are living beings. Biologist Richard Dawkins assigns the main role in the origin and existence of life to a “replicator” capable of indefinite self-reproduction. © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_1

3

4

1 Basics

Humberto Maturana and Francisco Varela argue that the main characteristic of living systems is their ability to carry out autopoiesis (self-maintenance), which is realized through the presence of an extensive network of chemical processes. Life is also defined as “a biological form of motion of matter, qualitatively superior to physical or chemical, but including them”; as an “evolving Darwinian chemical system”; as “an open system capable of lowering its internal entropy using the free energy of the surrounding space”, and so on. There is a minimal definition consistent with many modern definitions: “Life is self-reproduction with variations.” The cornerstone here is the capability of living organisms to self-reproduce. In 1994, NASA presented the official definition of life which is used in their efforts to find life in the Universe: “Life is a self-sustaining chemical system capable of Darwinian evolution.” Several key concepts are emphasized here: system, self-maintenance, evolution. The features common to these two definitions are the role of systems, self-reproduction, self-maintenance, and evolution. There many are other interesting definitions. In several cases, life is defined through terms such as “substance”, “system”, “phenomenon”, “process”, “living bodies”, “organisms”, “information”, “reproduction”, “autopoiesis”, “evolution”, etc. At the same time, no single common opinion and no single generalizing definition has yet been put forward. This also means that there is still no complete understanding of this amazing phenomenon. A fundamentally different approach to understanding the essence of life is to study the features of its manifestations at the supra-organismic levels of organization of the living. This approach was advocated by Vernadsky. In his doctrine of the biosphere, he emphasized the importance of studying the “aggregate of organisms”, and their complexes at the biocenotic and planetary level. That is, he proposed a view of life on Earth as an integral system comprising a set of organisms that interact with each other and with the environment. But none of these definitions introduces a concept of individual life and death, despite the fact that all living bodies suddenly appear from a parental organism and are inevitably mortal. While the life of an organism is based on the sustained run of a set of physical, chemical, and biological processes aimed at maintaining its existence, its death is the irreversible cessation of the main processes and functions that support life, followed by the subsequent disappearance of the given organism. The process of dying and death is a hereditary property of every organism and is a natural inevitable event after a certain period of time. Therefore, the sudden occurrence of daughter organisms, their gradual dying and inevitable death are among the most important characteristics of individual life. This is what fundamentally distinguishes living bodies from the inanimate world. Inanimate objects, such as a stone, a house, or a car, do not appear as the result of reproduction by a similar parental organism, but rather as the result of the action of external forces. They may exist for a while, but will invariably be destroyed by entropy without that external support. They have no intrinsic ability for self-recovery. They do not master any independent internal capacity to fight entropy and maintain integrity, and they have no autonomous, internally defined cycle of existence. Consequently,

1.2 The Main Feature of the Earth

5

living bodies possess several fundamentally important characteristics that distinguish them from non-living ones: the sudden appearance as a result of reproduction, the fight against entropy by means of self-recovery, and an inevitable programmed death. Thus, life is a very complex and intricate phenomenon. Obviously, this concept includes the existence of both individual living bodies and the planetary system of life which they create. These biological systems have certain common characteristics, but they are in general very different (Table 2.1). The common factors are the ability to exist relatively autonomously, the ability to self-sustain through reproduction, and the exchange of constituent units, while the fundamental difference is that living bodies are short-lived, mortal, and multiplying, while the planetary system of life they form is virtually immortal and has existed for billions of years. Due to the different properties of living bodies and the planetary system of life, there are difficulties with the perception and understanding of the phenomenon of life per se. General uncertainty remains despite the determination of many regularities. When we discuss immortality in the materialistic sense, some scientists assume such a possibility in the primitive organisms. For example, the existence of some sort of “immortality” can be speculated in unicellular organisms constantly multiplying by division. In this case, the cell does not die, but simply divides into two daughter cells. No corpse means no death, and no death means immortality. This statement is controversial. If we take a look at microorganisms under the microscope, we will see subpopulations of young dividing cells, but we will also see old cells that have lost this ability, and we will see dead cells. The possibility of biological immortality for complex multicellular living creatures is not even considered. So, is the physical immortality of living bodies and biological systems in any way possible? This question can be answered only after an unambiguous answer to the main question: What is life?

1.2 The Main Feature of the Earth Apparently, life is a unique natural phenomenon in the Solar System, but a very widespread one on our planet (Fig. 1.1). At the same time, life is not an eternal static phenomenon on Earth. It arose at a certain stage in the development of our planet, about 3.5 billion years ago, as a result of biochemical evolution, developed over a long time, and continues to evolve further today. Life has a cellular basis and is extremely widespread on our planet, despite the range of dramatically different physical and chemical environmental conditions. As a result of adaptation and evolution, living organisms are incredibly diverse in size, complexity of structure, multicellularity, level of organization, characteristics of metabolism, and vital activity. This variability allows them to occupy almost any ecological niche on Earth. Living organisms can live “above,” “in,” and “under” the ground, “above,” “in,” and “under” water, in the air, in rocks, in other organisms, in ice, in hot geysers, and so on. They are found under enormous pressures at depths of several kilometers in the ocean and at altitudes of several kilometers in extremely

6

1 Basics

Fig. 1.1 Life flourishes on the planet Earth, and probably nowhere else in the solar system. A cell is the universal form of its manifestation. It contains the main substrates of life: nucleic acids, proteins, and water

rarefied atmospheres. Manifestations of life are observed at extremely low temperatures, down to − 50 °C, and also at extremely high temperatures, approaching 100 °C. Certain species of molds (belonging to the genus Aspergillus, Cladosporium, and Helmintosporium) are known to live on the cooling coatings of nuclear reactors, able to withstand enormous doses of radiation. One might say that the Earth is thoroughly “infected” with life. It is infected to such an extent that basically nothing would be able to destroy it on our planet. The substrates of life are molecules of nucleic acids and proteins, the properties and functions of which (in the aquatic environment) provide the whole of its extreme diversity. Only catastrophes on a cosmic scale, which would lead, for example, to an increase in the temperature of the Earth’s surface above 100 °C and the disappearance of water, could destroy life. Humanity, despite its global influence on living and inanimate nature, would not be able to destroy life. Even a nuclear war and the subsequent “nuclear winter” would destroy only intelligent life and hundreds or thousands of various species living on Earth. But many viruses, microorganisms, and more complex creatures that inhabit, for example, strata of the Earth or the ocean depths, could easily survive this “local catastrophe”. Thus, as a qualitatively unique form of matter, life will naturally exist for as long as the necessary conditions for aqueous solutions of nucleic acids and proteins remain on Earth. The fact that life is only present on the Earth is determined by the planet’s size and specific location. This particular distance to the Sun ensures a certain temperature and other physical parameters for the existence of organic substances and for the liquid state of water, which enables the existence of the “nucleic-protein bodies”.

1.2 The Main Feature of the Earth

7

The dimensions of the Earth are optimal for gravitational retention of the atmosphere, which is necessary for the relative stability of the physicochemical factors of the environment that surrounds living organisms. The atmosphere is not only an “umbrella” against otherwise disastrous ultraviolet radiation and meteorite bombardment. It also helps to maintain the temperature on most of the Earth’s surface in the range 0 to 100 °C. In this temperature range, water is liquid (and not solid or gaseous), which is an essential condition for the manifestation of life. Although the substrates of life—nucleic acids and proteins—can retain their vital potencies at even lower temperatures, even temperatures close to absolute zero, water in a liquid state is still required to manifest the potential of life. The biochemical reactions, processes, metabolism, and functioning unique to living organisms are provided primarily by biological catalysts—the enzymes. These molecular machines are key protagonists in the way life plays out on the cool Earth. They create conditions for the ultra-rapid course of a limited number of biochemical reactions at moderate temperatures, increasing their probability from minimal fractions to a hundred percent. Moreover, such reactions require minimal amounts of substrates and produce solely the required products. Qualitative selection of enzymes determines all the features of metabolism, function, and the direction of the flow of matter and energy, as well as constituting a particular living body. Nucleic acids provide this qualitative composition of enzymes through a special set of genes and mechanisms of differential expression. Chemical energy is required to enable the action of enzymes, and also for a variety of processes and functions. Such energy is produced continuously in the processes of oxidation of nutritives or through the process of photosynthesis in plants. The manifestations of life may be imperceptible or even completely absent. For example, a complete cessation of vital processes in some organisms is possible through anabiosis. Single-celled organisms, small invertebrates, spores, and plant seeds can be in a state of anabiosis for many years. Long-term preservation of their structure is possible under conditions of low temperatures and virtually complete dehydration. The most important thing, however, is the possibility of preserving the structural and functional state of DNA and proteins. Hence, when they return to normal conditions, all vital processes are restored. They come to life. Viruses are also able to exist in a state of anabiosis for a long period of time, preserving the integrity of their nucleic acids. They only manifest the features of a living body after entering the cell of a host. These facts support the possible existence of “latent life” on cosmic objects (in the form of rather stable nucleic acids) that may have brought it to Earth billions of years ago. The life of organisms is an intermittent, unidirectional process. A process is a course or development of a phenomenon, a sequential change of states and stages of development of something. In this case, it is a process of continuous appearance, development, and withering away of old individuals on the basis of reproduction and the formation of new ones. The process comprising the life of bodies is headed in one direction—from the past, through the present, into the future. It is realized in an irreversible change of the phases of ontogenesis inherent in every living being.

8

1 Basics

However, the phenomenon of life is a continuous process. Immortal genomes are transmitted during reproduction with minor changes from one mortal body to the next, from one generation to another, over millions of years and billions of generations. Generations of organisms are continuously replaced by subsequent generations. This exchange of living bodies and changing of generations is an amazing phenomenon, characteristic only of the network of living organisms, and an amazing property intrinsic to life as a phenomenon. This continuous process began from the moment there first emerged a stable system of living bodies; it never stopped, it continues now, and there is no end in sight. Every organism, as a carrier of life, exists only as an integral part of the ecosystem that includes its habitat. Redistribution of matter and energy occurs only in the organism-environment system. Therefore, living matter and the area of its existence must be considered as a large unified system. Based on the ongoing processes of constant redistribution of matter and energy within such a system, life can no longer be considered merely as the existence of autonomous organisms, but rather as a global planetary system in which these organisms are only constituent parts. Life has an informational basis, since reproduction, development, functioning, and evolution are based on informational genetic processes (Fig. 1.2). In particular, during their temporary period of existence, individuals pass on the genetic program of development of their own kind through the DNA of gametes (sexual reproduction) or through the DNA of a body part (asexual reproduction). In their turn, individuals of the new generation grow and mature on the basis of DNA programs, then again produce gametes and reproduce—a new cycle of life begins on the basis of nucleic acids. This goes on and on, as long as there are conditions for survival and reproduction. Continuity of genetic material, despite the changing generations of individuals, is one of the most important characteristics of the phenomenon of life. This ensures the “intermittent continuity” of life. Despite the mortality of the carriers, they manage to generate a transitional form of life through the genetic material of gametes, spores, cysts, or other compact and very stable units. That is, life conventionally occurs on two levels. One is a continuous genotypic life hidden from view. It is the existence and functioning of a network of the virtually unchanging genomes of all types of living organisms. The other is the visible intermittent phenotypic life, manifested by the existence and functioning of the network of all living bodies (phenomes). Since phenomes are manifestations of the informational potential of genomes, we can say that various forms of cells and organisms are a kind of phenotypic framework for genomes. Life is very variable and is engaged in a process of constant evolution. Countless species of living organisms have changed on Earth over hundreds of millions of years. Different groups of organisms were at the pinnacle of evolution at various times: primitive organisms, plants, fish, dinosaurs, predatory mammals, and today humans. In principle, these are just the discrete links in one chain of the gradual development of life. Although the phenotypes of these organisms differ tremendously, their genotypes have undergone only slight molecular changes, and these are insignificant in comparison with the changes in the phenotypes. In the course of evolution, only the quantitative composition of nucleotides and the chromosomal

1.2 The Main Feature of the Earth

9

Fig. 1.2 The Earth is literally permeated with life and covered with a continuous network of DNA. The system constituted by these molecules is the main, practically indestructible substrate of life

composition of karyotypes change periodically. Moreover, these changes affect only part of the genomes and do not always correlate with phenotypic rearrangements. Hence, relatively small evolutionary changes in the genetic apparatus are significantly amplified in the process of realization of hereditary information, leading to considerable modifications in the phenotype (this phenomenon was first noted by N. Timofeev-Ressovsky). Thus, life on our planet is an extremely ancient, extremely widespread, extremely diverse, extremely stable, and extremely variable phenomenon. The reason for the existence of this tremendous diversity of phenomes, involving millions of species of organisms, is the presence of the same enormous number of versions of their genomes. On the basis of a common origin and a single principle organizing the genetic apparatus, it becomes clear that the genomes of all species of living bodies are united into a single genosphere—the information system of the global genome. Then the totality of all phenomes, all the organisms living on Earth, can be addressed as a single phenosphere—the material system of the global phenome (Fig. 2.5). Interacting and mutually conditioning each other, the global genome and global phenome form the unified planetary life system. Therefore, we can say that the essence of life is a process of continuous existence via the development of very stable dynamic complexes of various genomes that contain specific programs for the controlled ordering of the surrounding material space and the creation of certain forms of subsistence as instantiated by the particular representatives of living species. Hence, the phenomenon of life can be represented conventionally as the integrated existence of two components (Fig. 2.6): • autonomous living bodies with individual life;

10

1 Basics

• a single planetary system of life, consisting of the totality of all living bodies on Earth. Despite some similar principles of organization, these two forms of the manifestation of life are very different and have many of distinguishable characteristics (Table 2.1). At the same time, they have the same physical and chemical foundations, which we shall discuss further below.

1.3 The Material Backbone of Life Living beings are an integral part of the developing nature. All biological processes are carried out in accordance with the laws of nature and the very existence of living organisms depends on those laws. Nearly all chemical elements of Mendeleev’s Periodic Table are found in various representatives of living organisms. The main components of living organisms are carbon, hydrogen, oxygen, nitrogen, sulfur, and phosphorus. Besides, oxygen, these elements are not the most abundant on the planet. Yet, they conform best to the conditions of living systems. It is these elements that form a variety of organic substances and basic macromolecules inherent in living nature, such as proteins, nucleic acids, carbohydrates, and lipids. Up to 70–80% of the mass of living bodies is water, together with various mineral and organic salts. Thus, all living organisms consist of the same atoms and elements as non-living objects. Moreover, the properties of specific compounds that make up cells and organisms do not differ from the properties of the same molecules in non-living systems. But specifically organized and ordered complexes of macromolecules, in the form of cellular compartments, already possess new biological properties. As a result, biological objects are very different from inanimate ones, since they have properties that are unique to them. For example, they are characterized by reproduction, nutrition, respiration, etc., which is in fact due to the controlled and ordered interaction of the molecules and cellular structures and cells that compose the organism. Cells are heterogeneous molecular systems. Macromolecules form the structural and functional units of cells, various organelles and compartments, by uniting in specific combinations and quantities, and interacting in an aqueous medium. This ensures the consistent patterns and orderliness of metabolic reactions and cellular functions. The precise orderliness of molecules is the basis of the structure and function of all cells. Organisms have a set of inherent physical and chemical characteristics. In particular, they possess discreteness and hierarchical structure, interaction and interdependence of parts. They also possess integrity. Organisms are based on molecular structure; they transform and use energy to perform work, and so on. The physicochemical basis of life means that we can study biological objects using the powerful state-of-the-art methods of chemistry and physics. This has resulted in the discovery of many molecular and cytogenetic mechanisms of life.

1.3 The Material Backbone of Life

11

Thousands of biochemical reactions take place in the body according to the laws of chemistry, such as the law of conservation of mass and energy. Almost all substances in the cell are dissolved in water. The principles underpinning the behavior of substances in solutions do not differ between a cell and a laboratory test tube. Almost all biochemical processes require enzymes that work according to the principles of chemical catalysis. Various factors, such as light, temperature, and pressure, have the same effect on biochemical reactions as they do on chemical reactions outside biological systems. Hormones, cytokines, and neurotransmitters are chemical molecules of a specific nature and structure. By binding to receptor molecules on the cell surface, they transmit certain signals and information, often altering the physical state of membranes and other molecular complexes. That is, the cells of multicellular organisms communicate using a physical and chemical language. The chemical interactions of the various molecules are the basis of life. Traits and properties of living organisms, encoded in DNA molecules, are stored and transmitted from generation to generation in the course of chemical processes. The essence of most of the mechanisms of biological processes can be reduced to biochemical transformations of molecules of certain substances and the formation of others. These changes are based on the processes of breaking and forming chemical bonds. The processes are in turn associated with the interaction or exchange of elementary particles and atoms of interacting molecules, primarily protons and electrons. The motions and interactions of molecules in living systems are based on such physical processes as diffusion and osmosis, which are themselves based on thermal motion. Many molecules and supramolecular cellular structures have strictly defined functionally significant physical properties, for example, polarity or hydrophobicity. Cell membranes have electrical potential, and the processes occurring in nerve cells conduct electric current. The flow of blood through the vessels is carried out according to the laws of rheology. Joints, skeletal bones, and muscles operate on the basis of mechanical principles. Energy transformations in living organisms obey the laws of thermodynamics. Physical laws determine the phenomena of vision, hearing, movement, conduction of nerve impulses, permeability to various substances, and much more. Living organisms, like everything else material, exist in a certain space and time. They are complex systems that exist on the basis of the global property and capability of all components to perform motion. The basis of all types of motion in living bodies is the thermal motion of molecules, which emerged simultaneously with matter at the moment of the Big Bang. Thus, it should be noted once again that living bodies possess physical and chemical characteristics, and all processes in living organisms occur are subject to the laws of physics and chemistry. These are the key physical and chemical characteristics and properties of living bodies: 1. discreteness, orderliness, and hierarchical structure; 2. interaction and interdependence of parts—integrity; 3. molecular basis of structural and functional organization;

12

1 Basics

4. the ability of molecules to move, interact, self-organize, and form ordered systems; 5. low entropy; 6. occurrence of the necessary molecules in a certain location in concentrations many orders higher than in the surrounding space; 7. strict coordination of chemical and physical processes based on sustainable information; 8. transformation and purposeful use of energy to do work. These properties of living matter determine the formation of the complex highly organized physicochemical system of a living body, which can defy the second law of thermodynamics for long periods of time. An ordered system of interacting molecules of living bodies underlies the basic molecular biological processes of metabolism. The following processes provide the biological properties and characteristics of living bodies: 1. nutrition; 2. secretion; 3. respiration; 4. growth and development; 5. irritability; 6. motility; 7. homeostasis and adaptation; 8. reproduction; 9. heredity; 10. variability; 11. evolution. All these properties are genetically determined and controlled by nucleic acids via specialized molecular processes. The abilities to think abstract, analyze, and synthesize, as well as create, emerge at a certain stage in the evolutionary development of higher mammals. This led to the appearance of intellect and the development of complex social behavior in humans. On the basis of biological properties, there thus arose a new form of life: intelligent life, perhaps associated only with humans. This form of life differs fundamentally from mere “bodily” life, thanks to a number of additional social properties and characteristics: 1. Intellect; 2. self-awareness; 3. language proficiency based on abstract signs; 4. abstract thinking; 5. self-study and self-programming; 6. the ability to selfknowledge; 7. the ability to control instincts; 8. the ability to consciously overcome the control of genetic programs of behavior; 9. a well-developed and complex culture of life; 10. the establishment of various social institutions; 11. cognition and global influence on nature; 12. science; 13. art; 14. philosophy and religion; 15. morality, ethics, conscience; 16. politics and economics; 17. behavior in society based on social laws and social values; 18. the social and spiritual attributes of a person are developed and realized on the basis of biological properties alone, in the process of training and education. Still, it is obvious that living organisms (including humans) are not something exceptional, but are part of the material world. They have the same atomic and molecular nature as inanimate matter. Their chemical components and the relevant principles of physicochemical interactions do not differ from those making up inanimate objects. They are distinguished, above all, by the high level of specificity of a particular set of molecules and their concentrated localization in a certain region of space. And most importantly, the formation of highly organized biosystems and the emergence of a qualitatively new level of existence of matter in the form of

1.4 The Energy Backbone of Life

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life are determined by the extremely precise genetically programmed ordering of these molecules, along with their complexes and interactions. At this level, living systems function according to more complex biological laws than their individual components. The fundamental difference between scientific and non-scientific (religious, mystic, etc.) points of view on the nature of life is that scientists do not consider life to be anything other than just another manifestation of nature. They consider life to be a distinctively organized part of nature that has the same material basis. Science also proposes the concepts and explains the laws behind the possible genesis of life. Thus, living matter is an integral part of nature that obeys the same universal physical laws as inanimate matter. These laws determine the presence of certain boundaries in the properties and characteristics of living beings, and unequivocally reject the possibility of mystical phenomena (levitation, resurrection, ascension, etc.).

1.4 The Energy Backbone of Life Life is hard work. It requires constant work by living bodies, bringing internal energy to bear against the disorganizing and destructive action of the physicochemical factors of the external and internal environment, as well as against the tendency of all systems to increase entropy. Work is also required for the massive, constant synthesis of a variety of organic substances needed to maintain structural and metabolic homeostasis. And an enormous amount of work is required to accomplish various functions like motion, respiration, nutrition, reproduction, and so on. In short, the concept of work is applicable to any process in living systems, from the molecular level to the level of the whole organism. Naturally, energy is required to carry out any kind of work. And carrying out such a vast and varied amount of work requires a lot of energy. Energy must be constantly absorbed by the organism, transformed, stored, and purposefully applied (see also Sect. 7.2.2). Energy consumption. Energy enters living organisms in two distinct ways. 1. Bacteria, protozoa, fungi, and animals consume energy from the surrounding space in the form of various organic substances. These substances are consumed in a variety of ways via nutrition. Absorbed organic macromolecules (proteins, polysaccharides, lipids) are digested. That is, they are disintegrated into nonspecific monomers: amino acids, monosaccharides, carboxylic acids, and so on, which serve as the sources of energy. The energy of chemical bonds is extracted from them in the form of protons and electrons in the process of gradual degradation of monomers of organic substances to H2 O and CO2 , and is accumulated in adenosine triphosphoric acid (ATP). 2. Plants and certain bacterial species consume visible light energy. The main source of radiant energy is the Sun. Plant cells have special organelles—chloroplasts, which contain specialized molecules, chlorophyll, that absorb photons. The resulting cascade of quantum and molecular transformations leads to the

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conversion of radiant energy into the energy of protons and electrons, and then into the energy of chemical bonds of ATP. Energy conversion. Animals have several universal metabolic pathways for the transformation of nutritional energy into the energy of chemical bonds of ATP. For example, let us trace the path for conversion of glucose, which is a key source of energy in many organisms. Glucose, formed from polysaccharides, undergoes stepwise oxidation in the cytosol of cells. This process takes place under anaerobic conditions. Specialized enzymes detach hydrogen molecules from the glucose molecule one by one. The six-carbon glucose molecule in the metabolic pathway of glycolysis is first converted into two three-carbon pyruvic acid molecules (and 2 ATP molecules are formed). Then pyruvate is converted by enzymes into 2-carbon molecules of acetyl-CoA, which are then completely disintegrated in the metabolic Krebs cycle of mitochondria into CO2 and H+ molecules, as well as e− . Hydrogen atoms detached from glucose are bound by specialized coenzymes NAD and FAD, which transfer protons and electrons to the respiratory chain of mitochondria. The energy of electrons moving along the chain is used to transfer protons into the intermembrane space and generate a powerful electrochemical membrane potential. The energy of this gradient then brings about the targeted diffusion of protons through “molecular machines” called ATP synthases. This highly sophisticated enzymatic complex synthesizes a significant amount of ATP by using the energy in this electric current of protons. Oxygen is used only at the terminal stage of disintegration of organic matter, at the end of the mitochondrial respiratory chain. Another highly refined enzymatic complex, cytochrome oxidase, catalyzes the process of binding oxygen, protons, and electrons. The result is water, where hydrogen has the highest oxidation state. A similar transformation path is characteristic of other organic substances that can serve as the energy supply for cells. In every case, the energy of chemical bonds in carbohydrates, proteins, and fats is: 1. “quantized”—free protons and electrons are formed; 2. converted into the electrical energy of moving electrons; 3. transformed into an electrochemical potential of H+ on the inner membrane of mitochondria; 4. converted into an electric current of protons by ATP synthase; 5. transformed into the energy of chemical bonds in ATP. Plant cells use a slightly different mechanism of energy accumulation and transformation. They use photosynthesis as the main process for converting the photon flux energy (electromagnetic radiation) into the energy of chemical bonds in ATP, and then into the chemical bonds of organic substances. The resulting ATP is used in the dark phase of photosynthesis to form organic matter. Energy supply and storage. Independently of the way it is retrieved, the majority of the energy in cells is ultimately accumulated in the macroergic bonds of ATP. Use of ATP as the main accumulator of energy results in considerable savings in the cell in terms of optimizing the number of operating mechanisms. ATP is a nucleotide and

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consists of adenine, ribose, and three phosphoric acid residues. Energy is accumulated not so much in phosphate bonds, but in the bonds of the entire molecule. The process of ATP synthesis occurs in the mitochondria. Here, a significant amount of it is accumulated and stored. This small, universal molecule can then spread throughout the cell and supply energy for the widest possible range of work. Purposeful use of energy. ATP plays a key metabolic role, as it is a link between energy transformation processes and processes that require energy consumption. Specialized enzymes, with ATPase activity, break down ATP in a targeted way (where and when required), and direct energy to perform particular work. Hydrolysis of ATP releases more energy than the hydrolysis of any other intracellular compounds. ATP is the main link between catabolic and anabolic reactions in cells. Primarily, ATP is involved in work aimed at maintaining the orderliness and homeostasis of the cells themselves. For this, the membrane mechanisms are supplied with energy for selective transport of various molecules into or out of the cells (and membrane cell organelles). This uses up to 30% of the energy of ATP. Synthesis of molecules necessary for the cell, such as amino acids, peptides, proteins, nucleotides, RNA and DNA, fatty acids, triglycerides, phospholipids, and so on, consume up to 50–70% of the total energy. In addition, energy is required to alter or maintain the shape and volume of cells, and to move parts of cells or the cells themselves. Processes of cell division and differentiation are also conducted with the use of the chemical energy of ATP, which ensures the growth and development of organs, tissues, and the body as a whole. All physiological processes and functions are supplied with energy by ATP as well. This includes muscle contraction, digestion and absorption, transport of substances and blood flow, respiration and thinking, and much more. Thus, in order to maintain life, all organisms must constantly consume, transform, accumulate, and purposefully exploit not only substances, but also free energy coming from the external environment. Organized transformation and use of energy and matter would be impossible without genetic information. The genome completely guides and controls the synthesis of the necessary enzymes and the building of the structural mechanisms required for these purposes. Purposeful flows of energy and substances enable the cells and the body to function, and they maintain a high degree of orderliness and homeostasis for long periods. If the flow of energy and matter into the body (in the form of food or light) slows or stops, its structure begins to gradually deteriorate, functions are disrupted, and the body eventually dies. Hence, living beings have a complex organization that can be maintained for a long time. Liquid, highly plastic, and vulnerable bodies that live in an unfavorable environment nevertheless retain their organization and properties for extended periods of time due to constant work against the natural forces of destruction. Thus, long-term maintenance of organization and homeostasis of living organisms, along with their reproduction and development, are entirely dependent on controlled transformations of energy.

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1.5 The Nucleic Acid Backbone of Life Nucleic acids are unique molecules essential to any organism (from viruses to humans) for storing, exploiting, and transmitting genetic information. Nucleic acids compose genes that determine and regulate the synthesis of proteins. In their turn, proteins determine the type and peculiarities of metabolism, patterns of growth and development, range of functions, and so on. The mechanism of replication of DNA with transmission to the next generation is the fundamental basis of reproduction for all living organisms. The flows of genetic and hereditary information determine the ordered processes of transformation of organic substances and the organization of the surrounding material space, which is the foundation for all vital phenomena. Nucleic acids form the backbone of genomes. The slightest abnormality in the structure of a nucleic acid can lead to adverse consequences for the organism or its death. There are two key groups of nucleic acid compounds: DNA and RNA. Both are biopolymers composed of nucleotide monomers. Each nucleotide consists of: (a) a phosphoric acid molecule; (b) a monosaccharide (ribose or deoxyribose); and (c) one of five nitrogenous bases: adenine (A), guanine (G), cytosine (C), thymine (T), or uracil (U). These giant DNA and RNA molecules are composed of chemically very similar nucleotides. They differ in the peculiarities of their chemical structure and in inherent biological properties. DNA (deoxyribonucleic acid). DNA is a very long macromolecule with a high molecular weight. It is a polymer that consists of hundreds of thousands of linearly interconnected nucleotides, which form chains. The sequence of nucleotides in DNA determines the genetic code. The DNA molecule consists of two long helically twisted chains. The chains are linked by hydrogen bonds between nucleotides. The order of the nucleotides in one strand precisely corresponds to the order in the other. In particular, T on one strand is always opposite to A on the other, and G is always opposite to C. Such a strict correspondence of nucleotides is called complementarity. On the basis of complementarity, information is accurately rewritten from DNA to RNA molecules during transcription or to daughter DNA molecules during replication. Two polynucleotide DNA strands are antiparallel: the 5' end of one strand is connected with the 3' end of the other and vice versa. Genetic information is read during transcription only in the direction from the 5' end to the 3' end. This chain is called a matrix chain, and contains directed sequences of the genes from which RNA is synthesized. A chain complementary to the matrix is called a coding chain; it serves as a standard for storing genetic information. It is the coding chain that possesses a decisive importance in the processes of replication and repair. The DNA molecule has unique properties: (a) DNA is capable of duplication. This process is called replication. In eukaryotes, it occurs during the S-phase of the interphase cell cycle. “Packed” copies of DNA in the form of chromosomes are evenly distributed to daughter cells during mitosis or meiosis. This ensures the reproduction process; (b) DNA implements its genetic information through the process of transcription. Herewith, DNA genes serve as templates for the formation of numerous

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RNA molecules, which are directly involved in the synthesis of proteins via translation. These processes provide growth, development, and metabolism; (c) from time to time, DNA is subject to mutation, resulting in a change in the structure of genes, which ensures variability and evolution; (d) DNA molecules are capable of recombination of the composition of genes, which ensures a variety of gametes and the appearance of offspring with new characters; (e) in the case of damage, DNA can restore itself. This process is called repair. As a result, genetic information is stably maintained through thousands of generations; (f) the structure of DNA is highly durable and stable. This ensures the stability of hereditary information, and the constancy of genotypes and phenotypes of living organisms over millions of years. RNA (ribonucleic acid). RNA molecules are constructed similarly to one of the DNA strands. They are polymers that consist of one chain of nucleotides, linearly linked to each other. Three main types of RNA are defined on the basis of molecular weight, structure, and function: mRNA (messenger RNA), rRNA (ribosomal RNA), and tRNA (transfer RNA). Ribosomal and transfer RNAs account for about 98% of all RNA molecules. All these types of RNA are formed on the genes of the DNA matrix on the basis of the genetic code and according to the principle of complementarity. All of them mediate the transfer of genetic information from DNA to proteins. mRNA. Messenger RNAs are formed on structural DNA genes (mRNA genes). mRNA transfers genetic information from the nucleus to the cytoplasm, where, together with ribosomes, they direct protein synthesis. They are called messenger RNAs because they deliver information (messages) for the generation of specific proteins. Messenger RNA molecules contain from 300 to 3000 nucleotides, which precisely repeat the genetic code of DNA. rRNA. Ribosomal RNA molecules are the largest RNA molecules, containing up to 5000 nucleotides. They have a linear or branched structure, and form loops of various shapes. rRNAs are formed on special regions of DNA (rRNA genes) that are located in the nucleolus. rRNAs are part of small and large ribosome subunits (together with ribosome proteins). In the cytoplasm, these subunits are combined by mRNA and form functioning ribosomes. tRNA. Transport RNA molecules are formed on special regions of DNA (tRNA genes). Small tRNA molecules have a shape resembling a clover leaf. Their main function is to transport amino acids to sites of protein synthesis (ribosomes). Besides the three main types, several other varieties of RNA have been discovered that are not directly involved in protein synthesis (snRNA, siRNA, aRNA, tmRNA, and etc.). They are very specific and participate mainly in post-transcriptional modification, DNA replication, and gene regulation. Ribozymes are RNA-based enzymes that act as biological catalysts. The above suggests that RNA may have been the backbone for the origin of life, even before the appearance of DNA and enzymes. Indeed, these molecules, besides just carrying genetic information, are also able to catalyze chemical reactions and regulate many molecular processes. It may be that short chains of RNA molecules emerged spontaneously under the conditions of the young Earth. Some of them may have acquired the ability to catalyze the reactions for their own reproduction (replication). Due to errors during replication, as well as mutations, some of the daughter molecules would have acquired differences

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from the parent molecules and begun to display new properties, for example, the ability to catalyze other reactions. Ribosomes provide further evidence that RNAs could provide the core material for the genesis of life. These are macromolecular structures in the cytoplasm of the cell, consisting of RNA and proteins, which are responsible for the synthesis of all cellular proteins. It turns out that, in all organisms, it is RNA located in the catalytic center of ribosomes that is responsible for the main stage of protein “assembly” by performing controlled connection of amino acids with each other in accordance with the genetic information. Consequently, ribosomes are unique structures that distinguish themselves within the cell by decoding the nucleic acid code and producing corresponding proteins. Thousands of different proteins are formed on this basis, providing all the inherent properties of living matter. Only the backbone of RNA could lead to the emergence of the world of proteins, cells, and multicellular organisms. Moreover, besides the protein synthesis, catalysis of chemical reactions, and regulation of metabolism, RNAs are able to protect plant and animal cells from the invasion of viruses. This function is performed by a special class of RNAs called small interfering RNAs (siRNA). They are so named, because their length does not usually exceed twenty-one nucleotides. In higher animals, such as mammals, small RNAs can also be involved in regulating the reading of genetic information from chromosomes. That is, many facts suggest that the RNA molecule may be the founder of life on Earth. “Stem molecules” of life. It is thus clear that nucleic acids provide the backbone of life. Or rather, life is based on the unique properties of nucleic acids; primarily, their ability to store and apply information in the form of genomes (see Chap. 13). As the main molecule of life, DNA is the custodian and supplier of genetic information. Thanks to DNA, living organisms and cells are able to multiply, grow, differentiate, and function. By analogy with stem cells, DNA could also be called stem molecules (Fig. 13.3), since they are the predecessors of all the other trillions of organic molecules from which the body is built and through which it functions. The horizontal DNA stem ensures the reproduction of living bodies. During reproduction, genetic information is duplicated via DNA replication, and then, as a result of mitosis or meiosis, it is transmitted to daughter cells and organisms. In this case, the genetic information becomes hereditary. The vertical stem of DNA ensures the formation and development of living bodies. Genetic information recorded in DNA molecules is applied in the process of individual development, where living bodies are built according to “genetic blueprints”. RNA molecules are mediators in information retrieval, which is realized through transcription and subsequent translation. The diverse bodies of diverse organisms are constructed from proteins. Thus, nucleic acid molecules are the material and informational backbone of the unity of all living. Their joint functioning with proteins conditions the existence of the phenomenon of life.

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1.6 The Protein Backbone of Life Proteins are large organic polymer molecules, consisting of amino acids linked in a chain by peptide bonds. They possess a complex structural and spatial organization. These molecules are the main constituent of any organism. For example, they account for up to 20% of the live weight of mammals. Another 70% of the mass of organisms is water, and the share of other inorganic and organic substances (amino acids, nucleotides, monosaccharides, carboxylic acids, etc.), including macromolecules (nucleic acids, lipids, and polysaccharides), accounts for only about 10%. Proteins perform a multitude of very important functions for life. They determine the structure and shape of cells, as well as all the cell and organelle functions, and they serve as tools for molecular recognition. The vast majority of enzymes are of a protein nature. They are directly involved in metabolic processes and the maintenance of all the functions of any organism. Mammals consist of up to 50 thousand different proteins. The individual and species-specific set of proteins in a given organism determines the features of its structure and functions, and the set of proteins in a differentiated cell of a particular organism determines the morphological, metabolic, and functional characteristics of that type of cell. Proteins are involved in virtually all metabolic reactions and functions, and likewise almost all micro- and macroanatomical structures of all living organisms. Structure. Polypeptide chains of proteins are built of 20 different amino acids, each with a pronounced chemical individuality due to the presence of a specific radical (for example, –H for glycine, –CH3 for alanine, –CH2 –SH for cysteine, etc.). This variety of amino acids and their combinations underlies the tremendous diversity of chemical and physical properties of the different proteins. Amino acids are linked together by peptide bonds. The carboxyl group of one acid interacts with the amino group of the other. As a result, various chemical groups of amino acid radicals are combined in different orders, and this determines the conformation and properties of the resulting protein. Several amino acids combined together are called oligopeptides. Polypeptides contain more than ten amino acids. High molecular weight polypeptides form proteins. Combinations of 20 amino acids can form a myriad of proteins that differ in size, structure, and function. The linear sequence of amino acids in a polypeptide is unique for each individual type of protein. The information needed to produce this sequence is contained in a region of a DNA molecule called a gene. Simple proteins consist solely of amino acids. Complex proteins contain substances of a different nature, for example, lipids (lipoproteins), carbohydrates (glycoproteins), and metal atoms (Fe, Mn, Cu, etc.). Many enzyme proteins also contain non-protein substances in the active site, called coenzymes. These are directly involved in chemical transformations. The spatial structure of a protein is determined by the sequence of amino acids and the structural peculiarities of their radicals. The specific spatial structure of the polypeptide chain is stabilized by various chemical bonds between its parts. Depending on the shape, proteins can be fibrillar or globular. Fibrillar proteins are filament-like. They are poorly soluble in water and rather stable under physiological

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conditions. Collagen, actin, myosin, and keratin are examples of fibrillar proteins. The majority of the proteins, however, have a globular structure. They have a spherical form and are highly soluble in water. Hemoglobin, albumin, and the majority of enzymes are globular proteins. The set of structural and functional proteins of a cell is called the proteome. This is a complete set of tens of thousands of different proteins that provide tens and hundreds of different kinds of metabolic function. The qualitative and quantitative composition of the proteome is determined by the genotype, which is the set of genes of the individual karyotype. A particular structure of an organism and its function depend on the amount, composition, and localization of proteins, as well as on the peculiarities of their configuration and the physicochemical characteristics of the surface and the active site (for enzymes). Certain sites on the surface or inside a protein, created by a consistent pattern of amino acid residues, form centers for the specific binding of other substances and determine its function. In particular, proteins can perform the following functions: 1. The structural function of proteins is associated with the formation of all the structures and components of cells: enzymes, organelles, membranes, the colloidal system of the cytoplasm, and so on. Enzymatic systems ensure the synthesis of a wide range of essential non-protein organic substances, like lipids, carbohydrates, amino acids, nucleotides, and so on. Proteins and their derivatives form the contents of cells and intercellular substances. Groups of cells and the mass of extracellular substances form integuments, skeleton, tissues, organs, and body parts. Everything together forms the organism. It is the proteins that are the means and elements for creating living bodies. 2. The catalytic function of protein enzymes is expressed in the selective acceleration of biochemical reactions by factors of thousands, thereby ensuring the metabolism and all functions of living bodies. 3. The regulatory function of hormones of a protein nature and peptides is involved in the fine tuning and coordination of many metabolic and physiological processes in living organisms. 4. The protective function of proteins in the body is manifested by the formation of its integuments and the membranes of organs and cells. Besides this, a range of proteins called antibodies are capable of binding foreign elements and cells (antigens) that have entered the organism, thereby facilitating their neutralization by immunocompetent cells. 5. Certain proteins perform a receptor function. They recognize external and internal chemical signals, transform them, and transmit them to the relevant part of the body. 6. The transport function is expressed in ability to carry a variety of substances to the sites where they will be used. For example, carrier proteins are involved in the transport of different substances through biomembranes, while hemoglobin carries oxygen and carbon dioxide around the body in most vertebrates.

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7. The motility function is provided by motor proteins, such as actin, myosin, kinesin, dynein, and others. They compose muscle tissue, and are responsible for cell motility, cytoskeleton reorganization, and so on. 8. The energy role is associated with the possibility of using amino acid residues of protein molecules in metabolic processes. Proteins have many other functions as well. But the key here is that proteins are the link between genotype and phenotype, i.e., the link between the virtual genetic program in the DNA molecule and the real material body created according to this program: genotype → protein → phenotype. Proteins are intermediaries in the implementation of genetic information, as well as a means and a key element of the creation of a living body. Proteins and nucleic acids determine and provide a fundamental difference between living organisms and nonliving bodies, which is the unity of the genome and phenome in one nucleoprotein body, i.e., the unity of the program (for building and running a living body) and its product, with which this program is implemented. Thus, all structures and functions of cells and organisms are directly or indirectly determined by proteins and their properties. Life would be impossible without proteins. Life on Earth may thus be considered to have a protein base. Hence, the definition of life as “the mode of existence of protein bodies”, given by scientists more than a century ago, has a solid foundation, although only if we include the now established role of nucleic acids.

1.7 The Aqueous Backbone of Life The origin of water in the Universe remains unclear. Just as it is unclear where oxygen came from, in the huge amounts needed to oxidize the most abundant element, hydrogen. The amount of H2 O in the Solar System is enormous. This is exemplified on our own planet. Most of the Earth’s surface is covered with water. The depths of the oceans reach several kilometers. A large number of seas, lakes, and rivers are found on the surface of the continents. The surface layer of the Earth is saturated with water. There are also numerous cavities filled with underground water. Gigantic glaciers cover the poles of the Earth. Our planet thus has massive reserves of water, most of which is found in a liquid state. To this should be added a significant amount of H2 O in minerals, in the atmosphere, and of course throughout the whole range of living organisms. The origin of the vast amounts of water on Earth is not entirely clear either. Primary formation of water required oxygen. The oxygen on Earth is believed to be of biogenic origin, originally generated as a result of plant photosynthesis. But living organisms, in particular plants, could not have appeared without water. This means that it was abiogenic oxygen (where did it come from in such huge amounts?) that ensured the formation of water. It is unlikely that such a volume of water was formed

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Fig. 1.3 The structure of water in different states of aggregation. Solid state (ice): the substance is structured, with the molecules rigidly connected to each other and inactive. Liquid state: the substance is structured, with the molecules weakly bound and highly mobile. Gaseous state (vapour): the substance is not structured, with the molecules separated by a large distances and moving extremely quickly, hence liable to denature biological molecules

as a result of chemical processes in the bowels of our planet. The most probable hypothesis for the appearance of water on Earth is the long-term bombardment of our planet by comets, over tens of millions of years. Depending on thermodynamic parameters, water can exist in three different aggregation states: solid, liquid, and gas (Fig. 1.3). Yet, only the liquid state of water has the properties required for the manifestations of life (Fig. 1.4). It is this state of aggregation in which the distances between molecules, combined with their high mobility, are optimal for the necessary physicochemical interactions. In the solid state, water molecules are interconnected and inactive, and this does not allow the course of biochemical processes. In the gaseous state, the energy levels of the molecules are too high and would be harmful to proteins and nucleic acids. Not a single living organism is known that could do without water in the liquid state. Moreover, water is the main substance of living bodies. On average, H2 O makes up 70% of the total mass of living organisms. The vast majority of substances in living organisms, both inside and outside of cells, occur in a dissolved state (see Fig. 1.5). In animals, water is contained inside cells, outside cells, and in body cavities. Extracellular water is a key component of the intercellular space, blood, and lymph. Intracavitary water is contained in cerebrospinal, intraocular, and pericardial fluids, among others. Water molecules are interconnected by hydrogen bonds and form a single-phase medium or a sort of mobile “universal ether”. It is here that all the mechanisms and processes of life are carried out. The importance of water in ensuring life processes is conditioned by its unique physical and chemical properties. First of all, water is a very effective solvent due to the high polarity of its molecules (Fig. 1.5). All organic and inorganic polar molecules (salts, gases, amino acids, proteins, carbohydrates, nucleic acids, etc.) exist in cells in a dissolved ionized form. Even insoluble substances change to a colloidal or emulsified state, which allows them to interact with the aqueous phase.

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Fig. 1.4 Temperature ranges of water in different aggregation states. Life manifests its vital properties only in the range of liquid water from 0 to 100 °C

Fig. 1.5 Schematic representation of the dissolution of solid crystalline substances by polar water molecules

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This significantly increases their mobility and reactivity, very important for ensuring metabolic and physiological processes. Substances attracted to water are called hydrophilic. In contrast, hydrophobic substances are not attracted to water and are not only unable to dissolve in it, but cannot even form an equilibrium mixture. The third group of compounds, amphiphilic, contain both hydrophilic and hydrophobic groups. These include phospholipids, a number of proteins, some amino acids, and others. Such compounds are important for the creation of complex structures like biomembranes in the aquatic environment. The heat capacity of water exceeds the heat capacity of any biological substance. Therefore, it acts as a regulator for the heat balance of organisms. Water can maintain and spread heat throughout the body over long periods. Water provides a capillary effect, manifested as fluidity in any direction through very thin channels, regardless of the effect of gravity and external forces. This is very important to ensure nutrition and metabolism between cells and blood capillaries, to ensure plant nutrition, and to enable the flow of intercellular fluids. Water facilitates the movement of dissolved substances in and out of cells. The high rate of Brownian motion in aquatic environments is one of the key conditions for the interaction of substances. Molecules of water and interacting substances undergo several kinds of very fast motion (see Fig. 1.6). Water is involved in many biochemical processes as a substrate, and is formed by many biochemical reactions as a product. Water and its ionization products, H+, OH−, and H3 O+ have a major impact on the properties of many cell components. In particular, they determine the structure of proteins and nucleic acids, the functions of enzymes, the organization of biomembranes from amphiphilic lipids, and much more.

Fig. 1.6 Molecular motion in a liquid aqueous medium is the basis for life processes. 1— Translational motion; 2—rotational motion; 3—oscillatory motion, 4—electronic motion. Moving molecules possess significant total energy (ε), which determines their reactivity

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Photosynthesis would be impossible without the photolysis of water. And without photosynthesis, the emergence and existence of the plant world, and hence also the animal world, could not have occurred. Finally, water is a habitat for millions of species of living organisms. Without water, only a temporary existence of life substrates is possible (in the state of suspended animation, anhydrobiosis), and there would be no actual manifestation of life. Almost all metabolic and physiological processes take place in the aquatic environment. Moreover, a constant concentration of water is required in cells for normal functioning. Violation of the water balance leads to pathological changes and ultimately to the death of the whole organism. Therefore, organisms have physiological and biochemical mechanisms for the regulation and maintenance of water balance. There are special barriers that prevent the free exchange of water. For example, skin in animals, bark in plants, cell walls in unicellular organisms. Higher animals have a thirst center in the hypothalamus of the brain that regulates the water content in the body. Terrestrial animals have developed mechanisms for maximum water retention in the body, in particular, reabsorption in the intestine and kidneys. At the cell level, the water content is regulated by the cytoplasmic membrane, with the help of special transporters of H2 O called aquaporins. The osmotic activity of water in blood and intercellular fluid is regulated by salts and by the amount of proteins synthesized by liver cells. It should be noted, that living organisms do not contain water in free form (as, for example, in a glass of tap water). Virtually all the water in the cells exists in a bound state. A significant amount of water molecules is bound and oriented in several layers on the surface of proteins, nucleic acids, carbohydrates, amino acids, anions, salt cations, and so on via the interactions with polar groups (–OH, –NH2 , –COOH, etc.). The inner content of cells is a colloidal solution (gel) that consists mainly of proteins. Colloidal solutions differ substantially from true solutions. In particular, gels have an internal organization (structure), ensured by an organized ordered orientation of water molecules around an organized structure of interacting protein molecules that form the internal skeleton of cells. In this way, “liquid” cells acquire the properties of solids: hardness, elasticity, and constant shape and structure, but at the same time retain high plasticity. Despite their 70% water content, mammalian cells rigidly connected by intercellular structures form nearly solid multicellular organisms. However, the presence of free water, along with the ability of bound water to participate in chemical and physical processes, determine the practically unhindered movement and interaction of substrates and metabolites. Moreover, the intracellular organization of water determines the formation of channels that enable directed movement of certain molecules. In addition, experimental data indicates the existence of controlled local phase transitions of cytoplasmic regions from the “gel” state to the “sol” state, and vice versa, which also allows the purposeful transfer of substances. In terms of the essential significance of water, we can say that all organisms on our planet are highly ordered, long-lived colloidal solutions. That is, water is an internal “ether” that integrates and stabilizes everything in biosystems. The physical peculiarity of intracellular water lies in its duality. It has an ordered liquid crystal structure while maintaining the low viscosity properties of liquid

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Fig. 1.7 The triangle of life. The backbone of life is the existence of aqueous solutions of proteins and nucleic acids. From this point of view, living organisms are highly organized, long-lived colloidal solutions

water. The property of being both a crystal and a liquid (to transit from one state to another), determines the precision and direction of transfer and interaction of internal molecules. This ensures the interconnection of continuous metabolic processes. The phase transitions of intracellular water can create that internal mobility of living matter which apparently constitutes the backbone of all the properties and mechanisms of living bodies. It is believed that this is how the targeted movement of various molecules like substrates, products, ATP, and so on, is provided in the cell. Life emerged, developed, and exists in a liquid aquatic environment. There is no evidence of manifestations of life without water (see Fig. 1.7). Thus, water is of absolute importance for life under the conditions on Earth and perhaps on other planets in the Solar System. This is why it is precisely H2 O that is targeted in the human search for life on planets and their natural satellites, since this is the main condition for the possible existence of a kindred form of nucleic acid-protein life.

1.8 The Thermodynamic Backbone of Life Thermal motion is a form of transformation of matter and energy that is especially important for living bodies. Temperature is a quantitative measure of this type of motion, and it determines the boundaries of life. The temperature range in the Universe is extremely broad: from almost absolute zero (minus 273 °C) in space to many billions of degrees in stars (see Fig. 1.8). On the Earth, it varies only between minus 88 °C in Antarctica and about 5000 °C in the Earth’s core. The temperature bounds on liquid water in oceans, seas, rivers, and groundwater, are much narrower and range from zero to tens of degrees Celsius. Vital activity of all living organisms is manifested exactly within this temperature range. Single-celled creatures, primitive multicellular organisms, fungi, plants, and poikilothermic animals cannot maintain a constant body temperature. Yet, they manifest life and activity in those temperature ranges where their enzymes are capable of stable functioning. Birds and mammals are able to automatically maintain a constant body temperature within very narrow limits, between 32 and 40 °C. Under such conditions,

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Fig. 1.8 Temperature range on Earth. 1—gaseous water, 2—liquid water suitable for life, 3—solid water

biochemical and biophysical processes in living systems proceed stably, at a constant rate, and regardless of environmental conditions. This gives these classes of animal a tremendous advantage. All physicochemical processes that support vital activity and ensure the functionality of cells depend to a greater or lesser extent on temperature. Temperaturedependent thermodynamic and kinetic constants determine the direction and rate of biochemical reactions, conformational transitions of biological macromolecules, phase transitions of lipids, changes in the structure of water, and other things. Any shift in temperature must inevitably change the rate of metabolism and disturb the initial ratios of the rates of individual components. The temperature is essential both for the existence of living bodies and for the existence of the phenomenon of life as a planetary system. Both phenomena manifest themselves in the same temperature range from 0 to 100 °C, which corresponds to the range of the liquid state of water (see Fig. 1.9). Nucleic acids and proteins, as substrates of life, can also exist for a long time in a frozen state, at temperatures virtually down to absolute zero. Under such conditions, they do not possess their

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biological properties and manifestations of life. Yet, they retain their structure and remain capable of manifesting their life potential. In this form, the “seeds of life” could travel through outer space on the debris of planets for millions of years. At temperatures above 100 °C, the phenomenon of life is absent, since the existence of living bodies becomes impossible. The majority of cellular macromolecules are destroyed under such conditions, and most importantly, there is a phase transition of water to a gaseous state at atmospheric pressure. Thus, it should be emphasized that life is manifested in a very narrow range of temperatures, close to the lower limit possible in nature (0 to 40 °C) (Fig. 1.9). At the same time, rather low biological temperatures are the key condition for the emergence and manifestation of life. At such low temperatures, chemical bonds are stable, and this ensures the existence of complex molecules. On the other hand, many biochemical reactions are impossible or can proceed only at very slow rates, which would be unable to ensure life processes. It is only through the availability of biocatalysts, which weaken chemical bonds in a targeted way and accelerate reactions by factors of thousands, that the necessary biochemical processes can occur. The whole spectrum of reactions that ensure life is only feasible due to biological

Fig. 1.9 Temperature limits of life

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catalysts. Thanks to the high reaction rates they procure and the specificity of their action, enzymes distinguish only a limited set from an unlimited number of possible reactions between countless molecules. In this way, enzymes “permit” and increase the rates of processes that would otherwise be unlikely at vital temperatures, thereby providing for the incredible phenomenon of life (see Sect. 1.9). In conclusion, the temperature determines the life of organisms and the course of most cellular processes more than any other factor of the external environment. All organisms are built up from chemical components and all life processes occur on the basis of chemical reactions subject to the laws of thermodynamics in a liquid medium. The temperature determines not only the rate of those chemical reactions, but also determines the structural rearrangements of proteins and nucleic acids, the phase modifications of fats, and the changes in the water structure itself. Low temperatures are thus the key condition for the emergence (see Chap. 8) and manifestation of life. Only the “inhibited” state of the environment with its sluggish transformations of matter and energy can allow highly specialized and carefully located enzyme molecules to precisely select a limited number of interrelated chemical reactions. These reactions then become biological processes and almost miraculously generate the living from the non-living. Thus, life is enabled by selected ultra-fast chemical reactions in a tiny enclosed space and at very low temperatures.

1.9 The Catalytic Backbone of Life Catalysis is the phenomenon whereby chemical reaction rates are increased by substances that can act repeatedly, but do not themselves change and are not consumed. At the same time, these substances facilitate and accelerate the chemical process, producing intramolecular and intraatomic rearrangements of substrate molecules by “loosening” their chemical bonds and forming unstable intermediate compounds (see Sect. 7.2.1). As already noted, living bodies exist in a very narrow temperature range, in the lowest part of Nature’s temperature scale. Under such conditions, many chemical reactions are impossible or run very slowly. Therefore, all biochemical and physiological processes in organisms are carried out with the participation of biological catalysts, called enzymes. These are protein molecules that accelerate the rate of biochemical reactions by factors of thousands, but are not consumed or changed themselves, only undergoing reversible structural transformations. The emergence of biocatalysts was a revolutionary phenomenon in the genesis of life. As a result, in the cold sea of serene chemical chaos, it was enzymes that caused the appearance of areas of rapid and organized transformation of substances, impossible under any other conditions. This became the backbone for the organization of biological processes directed by enzymes and the formation of the organized closed space and orderliness provided by cells.

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1.10 The Systemic Backbone of Life A system is an association of interconnected elements that are objectively or conditionally distinguished from something else. When we speak about biosystems in this chapter, we will mean only living bodies, that is, cells and multicellular organisms. After all, it is obvious that not all biosystems are living organisms. For example, an ecosystem is a biosystem, yet it is not a living body. The endoplasmic reticulum of a cell is also a biosystem, but likewise, it is not a living organism. A cell is a complex multilevel system (see Chap. 4) that consists of a large number of diverse, strictly ordered, interacting molecules. Molecular complexes form organelles, which are constituent parts of the cellular system. Cellular organelles are structurally and functionally interconnected. They exchange matter, energy, and information with each other. The inner space of the cell is divided by biomembranes into compartments, such as the nucleus, mitochondria, lysosomes, and so on, where only a specific set of reactions takes place. Multicellular organisms also have several levels of organization. They consist of body parts, organs, tissues, cells, intercellular structures, fluids, etc. Moreover, the lower levels of organization determine the structure and functions of the higher levels, which, in their turn, control the lower levels. The vital activity of cells can be carried out only under conditions of coordinated communication between them. Cells constantly interact with each other and with the environment. There is a constant exchange of matter, energy, and information between the environment and cells. The processes whereby cells interact with each other provide a spatiotemporally ordered, coordinated course of all metabolic and physiological processes, both in the cells themselves and in multicellular organisms. Organisms and cells must constantly exchange substances and energy with the external environment, and replace worn out and damaged structures with new ones. Otherwise, over time, the high level of their order would be disrupted, leading to the death of the system. Such thermodynamic systems, which constantly receive an influx of matter and energy from the outside, are called open systems. From a thermodynamic point of view, a cell or an organism is a highly organized open non-equilibrium system that continuously interacts with the external environment. That is, it converts the chemical energy of food into the energy of biochemical and physiological processes, and releases unused energy and unorganized matter in the form of a heat flow and waste into the external environment. Moreover, the interaction of a living system with its environment is cognitive, that is, determined by its own thesaurus (see Chap. 13), individual demands, and organization. Systems have a number of physical characteristics called parameters. For example, living organisms are characterized by temperature, size, volume, qualitative and quantitative composition of proteins, and much more. The set of parameters inherent in a given system determines its thermodynamic state. A change in one or more of these parameters is called a thermodynamic process. If the parameters can change reversibly, either spontaneously or under the action of external forces, then

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such systems are called non-equilibrium systems. All biological systems are nonequilibrium systems. That is, they can change spontaneously or under the influence of various factors, temporarily altering the course of processes and the state of the entire system. Living bodies are a kind of excited system, since their high level of structural organization possesses large amounts of internal energy. This internal energy is constantly lost in the course of metabolism due to its dissipation and the uncontrolled thermal destruction of system elements due to the chaotic thermal motions of molecules. This means that biosystems are dissipative. They constantly undergo processes of energy transition from ordered to chaotic motion. Such systems operate outside of equilibrium. Consequently, spontaneous processes in living systems at any moment are associated with an increase in entropy and with destruction. Therefore, in order to survive, biological systems must artificially maintain their organization with a constant inflow of free energy and the necessary substances. The slightest changes in the supply of energy or matter lead to disruption of non-equilibrium living systems. So, macromolecules and their complexes at the temperatures conducive to life tend to be labile and unstable. The organization of living systems at these temperatures is only preserved through anabolic processes that continuously eliminate chaotically arising defects associated with thermal and other types of destruction. This means that living systems continuously work against their own destruction, guided by the program of their genetic information. Organisms, although non-equilibrium, are nevertheless quite stable systems. That is, their parameters remain unchanged for a certain period of time. As already mentioned, this is ensured by the constant exchange of matter with the external environment and the use of free energy. Moreover, in fully formed organisms, the consumption of matter and energy corresponds to their utilization and output. For example, a living system must be constantly supplied with such components as water, salts, oxygen, and various organic substances, since the body cannot exist without them due to their constant use. At the same time, waste products such as CO2 , harmful metabolites, and heat have to be removed from the system. Living bodies feed on ordered matter, emitting less organized “waste products”. Biosystems are self-organizing. Ordered functioning structures are formed via the purposeful use of free energy and matter. Furthermore, the structure of this organization is determined by internal regulation within the system. The processes of self-organization of biological systems are controlled by genetic programs. This is especially evident during embryogenesis, when a complex highly ordered organism emerges from a single cell in a short period of time as a result of genetically determined processes of morphogenesis and differentiation (see Fig. 13.2). Living systems are hierarchical. They have several levels of organization, each of which is interconnected and dependent on the previous one. Through certain processes, the molecular genetic level determines the organization and functioning of cells; interacting cells determine the organization and function of tissues and organs; interdependent and complementary systems of organs and tissues form an organism. Everything in the body is interconnected within one space and is controlled by specialized systems and processes.

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Biological systems are cybernetic. They function and are regulated on the principles of generation and use of information. A cybernetic system is an organized and ordered set of interconnected and interacting elements, capable of generating, perceiving, memorizing, processing, and exchanging information. For example, living bodies perceive information from the external environment, process it, and respond appropriately. The concept of information is one of the most general scientific concepts. The father of cybernetics, Norbert Wiener, said that the only way to describe information is to imagine a situation where one subject (object) transfers something to another without losing it. The transmitted thing will be information. Organisms are dynamic systems. They exist on the basis of constant movement and work carried out by their constituent elements. The state of such systems is constantly changing over time. The development and behavior of living systems is, in principle, probabilistic and nonlinear. But in specific cases, the dynamics of the body’s reaction becomes linear on the basis of genetic programs and selectively catalyzed processes. In nonlinear systems, minor changes in any parameter can lead to serious unpredictable consequences for the whole organism. A living system is organizationally closed and is characterized by nonlinear dynamics, which allows the emergence of a new order and properties at critical points of instability. This property is called emergence and is characterized by the appearance and presence in a system of special properties which are not inherent in its individual elements. This expresses the irreducibility of the properties of a system to the sum of the properties of its components. This characteristic of a system is also called holism, systemic effect, or superadditive effect. We can say that life is an emergent property of the system of the material world which is not characteristic of any part of it, but arises when many elements are organized together. Therefore, reductionism, as an attempt to assess the phenomenon of life only from the point of view of physics and chemistry, or by studying separate parts of such a complex biological system, cannot provide a comprehensive perception or explanation. Living systems possess mechanisms of self-production, self-regulation, and regeneration which maintain their integrity and the constancy of their internal environment, known as homeostasis. That is, living systems are capable of autopoiesis, which is the ability to self-repair via internal forces and impulses. Maintaining the internal environment of the system ensures the stability of metabolic and physiological processes and a relative independence from the external environment. When the conditions of the external and internal environment change, the body quickly adapts to them via the mechanisms of self-recovery that maintain homeostasis. The stability of biological systems and regeneration processes are also controlled by the genome. An organism is an open system, but together with the environment it forms a closed system, where entropy increases in accordance with the laws of thermodynamics. In this case, the law of conservation of energy and matter determines the constant circulation of matter and energy of animate and inanimate nature. After the cessation of their vital activity, organisms give back to the environment everything they have taken, and the total amount of matter and energy of the system is preserved. Living “islands of orderliness” are destroyed, fitting into the overall pattern of the entropy

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increase in the Universe. Individual living bodies cease to exist, but new ordered biological systems emerge on the basis of reproduction and development. Planetary life on Earth is also a highly organized system. It consists of an organized mass of many types of living bodies in close relationships. However, this system has its own additional specific characteristics (see Chap. 2).

1.11 Compartmentalization Compartmentalization is an important method and mechanism of organization. This is a natural demarcation of the internal space of living systems into structurally separate parts (blocks). It allows for the simultaneous occurrence of many thousands of biochemical reactions (often oppositely directed) and the performance of numerous functions concurrently and in a coordinated manner. Parts of organisms or cells have their own functions, but they are in close connection and interaction with each other, which allows them to perform complex acts. The advantage of this block principle is that cells or organisms in diverse conditions can use different combinations of structural and functional blocks, forming dynamic functional systems to perform and maintain a wide variety of functions. About half of the total volume of eukaryotic cells is divided by membranes into compartments, many of which are known as cell organelles. The main types of compartments in the whole range of eukaryotic cells are as follows: nucleus, cytosol, endoplasmic reticulum, Golgi apparatus, mitochondria, lysosomes, and peroxisomes (plant cells also contain chloroplasts). Each block contains specific enzymes that selectively catalyze only certain biochemical reactions, which determine its unique functions. The inner membranes, separating the internal space and containing specific enzymes, enable functional specialization of the various parts of the cell. This plays a decisive role in the way the various processes are ordered. For example, cell nuclei contain the bulk of the genetic material and are the main site for nucleic acid synthesis. The cytoplasm surrounding the nucleus consists of the cytosol with cytoplasmic organelles. Generally, the volume of the cytosolic compartment is slightly more than half of the total cell volume. It is here that all proteins are synthesized and most metabolic reactions take place. In these reactions some molecules are destroyed, while others are formed, providing the necessary building and functional blocks. About half of all cell membranes are enclosed by a labyrinth-like cavity called the endoplasmic reticulum (ER). Numerous ribosomes are located on the side of the ER facing the cytosol. Ribosomes are involved in the synthesis of the whole range of proteins. Lipids are also synthesized there, but in the hydrophobic area of the ER. The Golgi apparatus consists of flattened membrane discs. Proteins, lipids, and carbohydrates enter their inner space, where they are modified by enzymes, then sorted into membrane sacs (vesicles) and sent to various places inside the cell or outside to be used. Mitochondria (and plant cell chloroplasts) contain specific enzymes and produce most of the ATP used for cellular work. The intermembrane space of mitochondria and chloroplasts (also a kind of compartment)

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is capable of forming a proton potential that ensures the functioning of ATP synthases, which are enzymes that produce ATP. Lysosomes contain enzymes that destroy wornout organelles, as well as particles and molecules absorbed by the cell from the outside by endocytosis. On the way to lysosomes, the absorbed molecules and particles must pass through a series of organelles called endosomes. Finally, peroxisome enzymes are involved in the neutralization of hydrogen peroxide and a number of other toxic metabolites. Compartments in different cells can be present in different ratios and have different volumes. The hydrophobic zone of biomembranes can also be considered as a type of compartment. Taken together, these compartments make up a very significant volume in the body. In addition to structuring cell volumes, this zone performs many other functions. For example, certain enzymatic processes take place only in the hydrophobic zone of membranes. Multicellular organisms. The intercellular space is a peculiar compartment of the organism. The volume of intercellular space in a human is several liters. It is a place for a range of specific metabolic processes, as well as the accumulation and modification of many nutrients. It is a transit space for oxygen, carbon dioxide, amino acids, glucose, hormones, and many other substances. The circulatory system is separated from the cells of the body by the walls of blood vessels and is also a compartment of the body with special contents and a huge variety of functions. The lymphatic system has a peculiar structure and internal content in order to perform its special functions. The fluid of the spinal canal forms a separate compartment together with the inner space of the ventricles of the brain with its own tasks. Each organ can also be considered a kind of body block. These are isolated parts of the body with specialized functions that have strictly defined sizes, shapes, localization, and structure. But, despite the spatial and structural separation of parts of cells or an organism, they function as a whole. This is enabled by the presence of special integration and communication methods using hormones, mediators, the nervous system, and so on. Compartmentalization is also typical for plants, and indeed for the representatives of other kingdoms, types, and classes of living organisms. Their bodies consist of cells, and the organisms themselves have vegetative and generative organs, vessels, and many other compartments and blocks. The block principle of organization can also be attributed to various processes and mechanisms, as well as functional molecules created by Nature. One of the examples of such principle is the presence of special complexes of various enzymes maintaining the replication process. The molecule of DNA, the range of basic enzymes, and the set of biochemical reactions and mechanisms are virtually the same in the majority of cells and organisms. The nucleoprotein ribosome, which is the key structure of protein biosynthesis, along with the associated biochemical process of polypeptide formation, also constitute a standard system or block that is used by all cells of all species of living bodies. Another advantage of the compartmentalization of biological systems is the possibility of progressive evolution based on the combination of already known and tested structural and functional blocks into new systems. In particular, the mechanism of

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aerobic respiration, which emerged much later, were derived from earlier anaerobic processes and structures. Many proteins, especially the complex ones, have a domain structure, or in other words, a block principle of structure. The genome of organisms also has a block structure, in many respects common to all living beings. Here, different systems of genes and combinations of nucleotides act as standard blocks. Recombinations of such genomic blocks have very significant consequences, primarily for the evolution of proteins, which are in turn structural and functional blocks of the proteome. A leap in evolution and the emergence of eukaryotic cells occurred through the combination of structural and functional blocks of different prokaryotes. Nucleated cells of unicellular creatures, autotrophs, and heterotrophs, appeared as a result of their combination and further development. The formation of colonies from the structural and functional blocks of eukaryotic cells led to a new leap in evolution via the emergence and development of multicellular organisms. Thus, the block principle of organization is commonplace in the construction, functioning, and evolution of all living systems, i.e., in all cells and multicellular organisms. It allows biological systems to respond to various changes in their conditions of existence in a quick and standard manner, to ensure homeostasis and survival. This is achieved primarily through the coordinated interaction of all standard parts of living systems, and also through the reversible formation of dynamic structural and functional systems from various blocks.

1.12 The Informational Backbone of Life It is well known that living organisms are highly organized open systems that exist on the basis of the exchange of matter and energy with the external environment. Recently, however, particular importance for the phenomenon of life has been attributed to the role of information (see Chaps. 13 and 14). Organisms emerge, develop, survive, improve, and interact with the external environment on the basis of information. Let us note several of the main flows of information in biological systems. 1. Flows of external information Organisms and cells exist in an ocean of information from the external material world. Absolutely everything around us carries enormous amounts of information. It can be a variety of physical, chemical, and biological phenomena, various types of motions and modifications, various waves, fields, flows of elementary particles, and much more. Living bodies are capable of perceiving only a certain, meager part of the surrounding information. They can distinguish only that part of information, for which they have special analyzers or receptors, as well as an internal system for analysis and application. Such a specific system of perception and analysis of semantic information in living systems can be called a biothesaurus (see Sect. 13.3). The term “thesaurus” is used in information theory to denote the totality of all information that the subject possesses. Different types and species of organisms have the

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same peculiarities of organization as their thesaurus, which means they also have the associated peculiarities of perception and processing regarding both the quality and quantity of information. They adapt and live in informational conditions that correspond to their thesaurus and ensure their survival. Organisms are able to analyze the perceived information and respond to it adequately. This ability of living bodies is called cognition. The perception and processing of information is based on the property of irritability and excitability. Subsequent adaptation is provided by physiological and behavioral reactions, a change in activity, or the formation of enzymes and other macromolecules required under these conditions. As a result, an adequate response to signals from the external world allows one to adapt and survive in changing environmental conditions. 2. Flows of intracellular information (a) Genetic information. Genetic information is stored in DNA molecules in the form of genetic code, as a precise sequence of nucleotide triplets. This information is used for the development and stable long-term maintenance of the structural and functional organization of organisms and cells as systems. Information is rewritten from DNA to RNA molecules, which provide the synthesis of the necessary structural proteins and enzymes. The resulting proteins ensure the manifestation of certain properties of cells. In other words, in this case, the flow of information in cells is directed from DNA to trait: DNA → RNA → protein → trait. The transformation and transmission of information is provided by the processes of replication, transcription, and translation, along with the subsequent stages of expression. The main life processes are provided on the basis of genetic information: reproduction, growth, development, differentiation, metabolism, and functions. (b) Molecular information. Intracellular structures, as elements of a complex system, are interconnected and function synchronously due to regulation by a variety of biologically active molecules. They carry signals for activation or inactivation of metabolic pathways and cycles, the transfer of substances, and activation or inhibition of enzymes. For example, there are several special protein factors that regulate protein synthesis, and the end products of biochemical cycles are usually allosteric regulators for the activity of key enzymes in metabolic chains. (c) Order information (phenotypic information). It is obvious that the very orderliness of the inner space of cells is a complex information system. Preset and inherited during cell division, this order of the cytosol and organelles structurally and informationally determines the physicochemical conditions for the course of standard biochemical and biophysical processes. The flows of intracellular information organize and ensure the coherent functioning of the complex contents of the cell body as a single whole. 3. Flows of intercellular information

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A complex multicellular organism includes hundreds of different cell types. They form various specialized groups, distinctively arranged in space. These cells form tissues, organs, and their functional components. The huge number of cells in a multicellular organism require the exchange of information to coordinate their various metabolic and physiological processes, including division, growth, and so on. The following methods of intercellular signaling can be distinguished: (a) Long-distance signaling through the fluids of the internal environment with the help of active molecules secreted by special cells. Hormones provide a good example. They are carried by the blood and act on cells located in various parts of the body. In plants, similar functions are performed by phytohormones. In this case, they are synthesized not by specialized glands, but by nearly all tissues, yet only under strictly defined conditions. (b) Contact signaling between adjacent cells using special signaling molecules. In this case, the cells secrete local chemical mediators (neurotransmitters, modulators, interleukins, prostaglandins), which are absorbed and destroyed so quickly that they manage to act only on the immediate environment of the producer cell. Contact signaling through gap junctions of neighboring cells is present in the heart muscle, providing all cardiomyocytes with close functional contact. This ensures synchronicity and a certain contraction force. In addition, contact chemical signaling underpins the functioning of chemical synapses, which are the predominant type of intercellular contacts in the nervous system. (c) Electrical signaling is used in the nervous system, where the passage of a signal within a single cell (neuron) is regulated by electrical mechanisms and the transfer of excitation from cell to cell can occur through a chemical, electrical, or combined synapse. In all these cases, the signals are chemical substances. These are molecules with specific structures. Even in the case of nerve tissue that generates and conducts electrical signals, at the final stage of contact with the target cell, the electrical signal is converted into a chemical one. Chemical signaling molecules usually degrade rapidly after being secreted and after their effect has taken place. Not all cells of multicellular organisms respond to chemical signals; only those that have special receptors. These receptors bind a signaling molecule and trigger a response. The flows of intercellular information ensure that the billions of individual cells in the body work as a single system. 4. Information flows between organisms (a) Between individuals of the same species. A whole system of communication and exchange of information exists among the representatives of the same species. This system is innate and extremely varied. It can be based on certain standards of behavior, facial expressions, signs, certain postures, forms, radiation, sounds, chemical signals, etc. Through active communication and exchange of information, animals of the same species successfully coexist in their territory. Exchange of information promotes reproduction and survival. Humans have developed a

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fundamentally new way of recording, storing, and transmitting information in the form of an artificial language using abstract symbols. (b) Between individuals of different species. Many forms of communication are shared between different species of animals. For example, a grin among predators or a rapid flick movement. Many animals have an innate ability to recognize their specific predators by appearance, smell, or behavior. Many also understand the language of marking habitats with excrement or secretions from special glands. Information flows between individuals of different species contribute to their coexistence and the formation of biocenoses. 5. Flows of hereditary (genealogical) information. In addition to the intracellular genetic flow of information, life is associated with the storage and use of information in successive generations of cells and organisms. In this case, genetic information becomes hereditary. Yet another information flow is thus directed from the DNA of one cell to the DNA of its daughter cells, from one organism to the other. This flow of information is associated with the process of reproduction. It is provided by the replication of DNA molecules in the mother cell, the formation of chromosomes, and the process of uniform distribution of hereditary material between daughter cells: DN A

−→

replication

two daughter D N A −→ two genomes mitosis

−→

cytokinesis

two daughter cells.

This information flow ensures the reproduction and long-term existence of populations of cells, organisms, and species. 6. Intragenomic and intergenomic information flows. Intragenomic (meaning the diploid genome of a certain type of organism) transfer of information occurs during reproduction and is associated with countless ways of combining the genomes of the father and mother, countless variants of DNA recombination during meiosis, and many variants of chromosome divergence. In addition, various mobile genetic elements are able to transfer different nucleotide sequences within their genome. The sum of the discrete genomes of living organisms constitutes a single system of the global genome (see Sect. 17.4). Despite the fact that individual genomes belong to representatives of different species and are quite diverse in their qualitative and quantitative composition of genes, as well as in the functional segments of nucleic acids, they all have the same background and a single principle of organization and functioning. There is still a structural and functional connection between such distant genomes, and the exchange of matter and information is maintained. The integrating factor of all discrete genomes is a group of mobile genetic elements (see Sects. 1.14 and 8.5.5), which includes viruses, phages, transposons, IS-elements, and others. Hence, there is sufficient evidence to suggest a continuous transfer and exchange of information both within one genome and between the genomes of different cells and even different species. Consequently, the global genome is a unified information

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system that ensures the selective expression of individual genomes, resulting in the construction of their diverse phenotypic environment. The first four flows of information ensure the life of biological bodies (phenotypic life), and the fifth and sixth ensure the continuity of life (genotypic life), that is, they condition life as a natural phenomenon.

1.13 Cellular Life From the point of view of structural and functional organization, the cell is an extremely complex biological system of macromolecules that possesses a high degree of order, as well as the ability develop, maintain integrity, and reproduce. It is a mobile, stable, open non-equilibrium system that manifests a comprehensive unity of structure and function. The content of a cell is so dynamic that it can be considered, not so much as a body, but as a continuous process. The backbone of cell life is the extraordinary orderliness of macromolecules, which form complex supramolecular structures (membranes, organelles) with specific functions. Proteins are the main macromolecules that compose cellular structures. Enzymes provide the basis for metabolism and all functions. In turn, the quantitative and qualitative composition of the cell is controlled and regulated by DNA and RNA molecules. The cell is a structural and functional unit of life for both prokaryotes and eukaryotes. Despite the peculiarities of the structure, metabolism, and functions of cells in different domains and kingdoms of the living world, they are all homologous. That is, they have a single principle of structure and organization (see Fig. 1.10). For archaea, bacteria, protozoa, some algae, and fungi, the concepts of cell, organism, and body coincide, since they are unicellular creatures. Colossal number of organisms of fungi, plants, and animals are multicellular, as they consist of thousands, millions, or even trillions of cells. Cells similar in structure and function form tissues, and tissues form organs. The functioning of trillions of cells in mammals is coordinated by the nervous, endocrine, and immune systems.

Fig. 1.10 Common pattern in the structure and organization of cells. 1. Bacterial cell. 2. Protozoan cell. 3. Plant cell. 4. Fungal cell. 5. Animal cell. (A) Genome (nucleus). (B) Phenome (cytosol and organelles). (C) Surface apparatus (membrane or cell wall), which is also part of the phenotypic framework of the genome. In all cases, the genome is the control center of life, the phenome is the executive system of life, and the surface apparatus is the system that isolates from and communicates with the external environment

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The size, structure, and shape of cells depend on the functions they perform. The diameter of most animal cells ranges from 10 to 100 μm (μm). The average diameter of a typical somatic cell is ~50 μm. The minimum cell size is determined by the minimum number of genes and corresponding proteins. For example, mycoplasmas have a tiny body size (0.3 μm), but they also have only around 300–500 different proteins. This, apparently, is the minimum required to create and maintain the smallest cell. The maximum cell size (approximately 100–200 μm) is determined by the possible maximum distance between molecules within the system which would still provide the necessary probability of interaction of molecules in the process of diffusion and movement along intracellular channels. This problem is partially solved by compartmentalization of the cell, i.e., dividing it into numerous small compartments, where the likelihood of interactions between molecules is significantly increased. Cell sizes are not related to the size of the organism. Thus, the liver cells of humans, mice, and elephants have approximately the same size. That is, the size of organs and the size of the whole organism of animals depend on the number of cells, and not on their size. The number of cells required to build an organism is diverse: from one (in unicellular organisms) or several hundred (in rotifers and some roundworms), to many billions, as in most mammals. Incidentally, there are amazing organisms that are capable of existing both as unicellular creatures and as a multicellular organism, depending on environmental conditions. This is a kind of transitional form between unicellular and multicellular life. Slime molds are an example. These are unicellular amoeba-like eukaryotes, leading a free lifestyle. However, under unfavorable conditions, they can easily gather into a single multicellular body, which then, in a more favorable environment, disintegrates with the same ease into many separate unicellular organisms. There are also cells that do not have a “complete” structure. However, such biological systems are either derivatives of cells or part of their life cycle. For example, erythrocytes are unique formations that subsequently lose their full-fledged cellular structure. They do not contain genetic material, mitochondria, and other classical cellular elements. They cannot reproduce. Thus, it is rather difficult to assert that the erythrocyte is a real cell or even a full-fledged living body. Apparently, it is more justified to consider erythrocytes as derivatives of full-fledged erythroblasts and consider them a part of the structural–functional cycle. Other biological systems that do not have a distinct cellular structure have also been described. For example, symplasts are formations consisting of cytoplasm with many nuclei, surrounded by a membrane. In particular, these are muscle fibers of vertebrates, the outer layer of the trophoblast of the placenta, etc. Syncytia (cocells) are systems of many cells interconnected by cytoplasmic bridges, which are formed, for example, during the development of spermatogonia. The long, extensively branching cytoplasmic hyphae of lower fungi containing nuclei also lack a true multicellular structure. Hence, the mycelium is a huge multinucleated cell. Certain chlorophyte green algae are structured similarly. We believe that all of the above exceptions to the rules of the cellular structure of living bodies are a consequence of the evolution and adaptation of cells and their systems to the conditions

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of the environment, or the need to create special functioning. Importantly, all of these generate essential conditions in a favorable cytoplasmic environment for the existence of nuclei that contain genomes. Cellular structure is crucial for the existence of the whole variety of organisms for the following reasons: 1.

From a number of different discrete living cellular bodies and their derivative intercellular substance, it became possible to create an infinite number of versions of multicellular organisms with new properties and functions, as well as new mechanisms of interaction with the external environment. This increased the possibilities for adaptation, survival, and distribution of the cells themselves, but also the organism as a whole and the genome used to create it. 2. Discrete organization of an organism from trillions of self-reproducing cells enables gradual replacement of dying or pathologically changed parts of the body (groups of cells) with new cells without disrupting the vital activity of organs or the organism as a whole. This significantly increases the viability of a multicellular body and its genome. 3. Cells similar in structure and function form tissues; different tissues form organs, providing a variety of functions of multicellular organisms. This increases the possibilities for survival and adaptation of multicellular bodies. 4. The distribution of functions between cells in multicellular organisms provides ample opportunities for evolution and development, as well as for the adaptation of organisms to their habitats. 5. The organization of a multicellular organism from small morphological unitscells with large surfaces favors the exchange of substances and energy with the external environment, as well as the interaction of cells with each other. 6. Molecular control of even the tiniest part of a large multicellular organism is maintained thanks to constant intracellular regeneration. 7. Only cells (as well as viruses, as cellular derivatives) have the ability to store and transmit genetic information, and also to realize it through protein synthesis. This was the basic principle underpinning the appearance and existence of cells, and then of multicellular bodies. 8. A cell is a molecular system capable of purposefully transforming matter and energy, and using it for work and the maintenance of its own structure for a long period of time. The life and functions of a huge multicellular organism are maintained at the level of molecular interactions within tiny cells. 9. A cell is a semi-autonomous system of interacting molecules in an aqueous media, which possesses a relatively minor dependence on environmental factors due to the fine organization of cytoplasm, the presence of a membrane, and the regulated maintenance of internal homeostasis. By maintaining their own molecular homeostasis, cells also maintain the homeostasis of their genome and the organism which they compose. 10. Cells are made of special organic substances that rarely occur in the free form. Only cells contain a sufficient “concentrate” of enzymes that enable specific and otherwise unlikely chemical reactions to occur on the basis of targeted

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catalysis. Such reactions proceed at tremendous rates, absolutely unbelievable at the temperatures at which life occurs. 11. Cells contain molecular and cytogenetic mechanisms for reproduction of their own kind. This ensures the maintenance of the qualitative and quantitative composition of the species of unicellular organisms on the planet for many thousands of years, despite the short fate of each individual life. The ability to reproduce is also the basis for maintaining the integrity and longevity of multicellular organisms, as well as the basis of both asexual and sexual forms of reproduction. Individual nucleic acids, proteins, and enzymes cannot determine the properties of life without a special environment in which the transformation of matter takes place. That is, neither individual nucleic acid molecules nor protein molecules are actually alive; it is only their complex system (genome), integrated into the highly organized colloidal matrix of cell protoplasm that is alive. The colloidal system of protoplasm, consisting of a multitude of structured elements, can be regarded as a matrix (we use this concept from the “cybernetic” point of view, defining a matrix as a set of structural and informational elements). Such a matrix is the “habitat” of the genome that provides precise directed flows of energy and substances, as well as their controlled interaction. The work of the molecular matrix is indirectly controlled by the genome through the synthesis of proteins. Here, the genome acts as a biological microprocessor. It becomes clear from the above that the basic components of living systems are not only the elements of the genome, but also the highly organized water-colloidal matrix of protoplasm. Thus, cells consist of two mutually integrated global parts: the genome, as the administration center of life, and the phenome, as the executive system of life in the form of its phenotypic framework. Thus, the cell is the unit of structure and function of the whole range of organisms. This is a microscopic semi-autonomous living body, representing a dynamic unity of ordered and interacting macromolecules and functional blocks, which form a highly organized self-sustaining system (phenome) based on the properties and requirements of the genome, acting on and actively exchanging matter, energy, and information with the external environment. Depending on the specific version of the genome, these microbodies have different molecular compositions and organizations into cell blocks. An enormous range of controlled biochemical and biophysical processes are continuously proceeding at very high rates inside the cells. These processes are primarily aimed at maintaining the integrity and self-preservation of the cells themselves, and hence also their integrated genomes.

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1.14 Non-cellular Life 1.14.1 Viruses Our planet is inhabited by millions of different species of living organisms. They exist in two types of life form: cellular and non-cellular. The vast majority of the enormous variety of species correspond to cellular life forms, while only viruses are non-cellular. Viruses are found in almost every ecosystem on Earth, but not all scientists consider them to be alive. Viruses are tiny bodies made up of a nucleic acid molecule (DNA or RNA), which is usually surrounded by an envelope of several protein molecules called a capsid (see Fig. 1.11). Some complex viruses are also covered with a membrane of cellular origin (supercapsid). The genome of the simplest viruses contains only three genes: a gene for the protein that causes rupture of the host cell membrane, a gene for the enzyme that replicates its own genome, and a gene for the capsid (envelope) protein. For example, Non-enveloped viruses

Enveloped viruses DNA double-stranded

DNA double-stranded

Adenoviridae Herpesviridae

Hepadnaviridae

Poxviridae

RNA single-stranded

DNA single-stranded

Parvoviridae

Coronaviridae Paramyxoviridae Bunyaviridae Arenoviridae

Polymaviridae Papillomaviridae

Circinoviridae

RNA double-stranded

Reoviridae RNA single-stranded Orthomyxoviridae Retroviridae

Rhabdoviridae Picornaviridae

Caliciviridae Togaviridae Flaviviridae

Filoviridae

Fig. 1.11 Classification and structure of viruses

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the RNA of the bacteriophage Qβ that infects Escherichia coli contains only 3500 nucleotides (several genes). The largest viruses contain 200–300 genes and up to several hundred thousand nucleotides. Viruses can exist outside living cells without showing signs of life. In this state, they are passive and unable to reproduce. However, viruses become rather active when they enter cells. They start to manifest such properties as reproduction and development. During infection, the nucleic acids of viruses enter the host cells through the membrane in different ways, depending on the type of virus. For example, they can enter by binding to membrane receptors and subsequent endocytosis (Semliki forest virus) or by injection (Bacteriophage lambda). The nucleic acids of many viruses interact directly with the cell’s genome. Other viruses replicate and translate in the cytoplasm (although an indirect interaction with the host genome is not excluded). The genetic information of the viral nucleic acids is transcribed and translated for the formation of proteins for its own protein envelopes using the biochemical mechanisms and energy of the host cell. Further, self-assembly of new viral particles from synthesized proteins and the nucleic acids of the virus occurs in the cytoplasm of infected cells. Thus, viruses are alive, when in the cell, but do not show signs of life outside it. Therefore, it is perhaps preferable to understand this, not as “live” viruses in a cell, but rather as highly active “living” nucleic acid molecules, since only they enter the cells, accompanied by just a few proteins. The body of the virus itself acts only as a delivery vehicle for the nucleic acids, which remain the main “actor”. Viruses are intracellular molecular parasites, affecting representatives of all kingdoms of living organisms. Once inside the cell, the virus, or rather its DNA or RNA molecule, changes the internal space of the host cell, forcing its genotype and phenotype to work for it. Many viruses do not cause disease, but some are highly pathogenic. They can cause serious diseases in animals, plants, and other organisms. Many human diseases, such as influenza, smallpox, mumps, polio, COVID-19, AIDS and many others, are caused by viruses. Some viruses parasitize bacteria and kill them. These viruses are called bacteriophages. In addition to a variety of viruses, plants can be infected by viroids. These small naked molecules of circular RNA, consisting of only a few hundred nucleotides, can parasitize and multiply in plant cells. That is, a tiny RNA molecule can be a minimal living body. This body also has a phenotype in the form of a certain number of nucleotide sequences, a ring structure, etc., as well as a genotype with a certain set of genes. Some hold the opinion that the emergence of such a specific, obligatorily parasitic form of life is associated with the early stages of evolution. A group of plasmid-like “creatures” arose from the individual nucleic acids of the first cells, initially from RNA and then from DNA, on the basis of their autocatalytic properties and their ability to replicate. They adapted to use the vital resources of various cells for the own reproduction. In the course of their evolution, “creatures” gradually increased their genome and acquired the ability not only to replicate and control protein synthesis for their own needs, but also to exist outside the cell and penetrate into other cells.

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1.14.2 Cellular-Viral System of Life Hence, viruses are not independent organisms, although they have a number of characteristics of living bodies. They form a single system with numerous cellular organisms. Their enormous diversity is explained by the parallel symbiotic coexistence and co-evolution of cellular and non-cellular life forms over billions of years. Several additional considerations confirm the existence of such a cellular-viral system of life: 1. 2. 3. 4. 5. 6. 7. 8. 9.

Viruses can reproduce and develop only in their host cells. Viral proteins are synthesized only in host cells. Genes of viruses encode proteins common to cells and viruses. Many viruses have envelopes that are derived from the cytoplasmic membranes of host cells. Only during their “life” in cells can viruses mutate, evolve, and change their properties and pathogenicity (as, for example, in the case of swine flu). Viruses exhibit tropism in the choice of the host and certain host cells. It is only by penetrating into a cell and exploiting cellular systems and metabolisms that viruses can assemble many copies of their bodies. There is a great similarity between the structures of viruses and certain elements of eukaryotic genomes, such as introns and transposons. Despite significant phenotypic differences between “non-cellular” and cellular forms of life, both have the same molecular basis (proteins and nucleic acids) and mechanisms (replication, transcription, translation), and this indicates their genetic relationship.

It has been noted already that viruses contain enzyme proteins that are related to their host cells. For example, avian influenza viruses contain neuraminidase, which destroys the glycocalyx of epithelial cells in the respiratory tract of animals. This is understandable, since the cycle of viral formation occurs in epithelial cells and uses the cellular mechanisms for the synthesis of these proteins for viruses. It is interesting that the cells themselves do not seem to fight against this. They lack any protection and even have special receptors. At least, the exact correspondence with the molecular mechanisms used by viruses to penetrate the cell suggests that these mechanisms were created by the cell itself. Only multicellular organisms are opposed to symbiosis with viruses, as they are threatened with destruction through a violation of the functions of cells in certain parts of the body. Thus, single-celled bodies existed in symbiosis with viruses and other mobile genetic elements before the appearance of multicellular creatures. This was a mutually beneficial coexistence. The cells allowed the viruses to multiply, and they themselves could use the additional genetic material they obtained. The formation of colonies and then of multicellular organisms began to contradict this symbiosis, since the introduction of some pathogenic viruses led to a violation of the integrity of the multicellular system. As a result, multicellular organisms developed defense mechanisms in the form of specialized cells. A conflict arose that lasted for billions

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of years and continues to this day. However, a compromise has apparently been found between multicellular organisms and many viruses, implying that the development of most viruses should not lead to the death of the host organism, and the host’s immune system should not in turn cause significant harm to viruses.

1.14.3 Molecular-Genetic Communication Hence, viruses are derivatives of cells, and not something that has emerged independently. They are totally dependent on cellular structures and processes. Their molecular constituents largely correspond to those of their potential hosts. Most likely, cells at a certain stage of evolution began to “produce” viruses. These were still prokaryotes, for which the derivatives of their genomes, such as plasmids, viroids, viruses, and then IS-elements and transposons, were a means (molecular mechanism) for the exchange of genetic information. These mobile genetic elements began to provide the processes underlying variability and evolution on the basis of a unified polynucleotide nature and a single system for encoding and decoding genetic information. That is, viruses and their analogues were most likely formed as a global molecular mechanism for the transfer and exchange of genetic information between the genomes of various cells (in this case, it is viruses, viroids, phages, and plasmids), as well as within individual genomes (here, transposons and IS-elements). They combined the processes of horizontal (from one genome to another and from one organism to another) and vertical (replication, transcription, expression) transfer of genetic information into a single whole, forming a unified network of circulation of bioinformation within the global genome system in the form of a set of discrete genomes of all living organisms. Despite the tropism of viruses, many of them mutate and acquire the ability to infect other types of cells or organisms. This can be seen in the examples of COVID19 and avian and swine flu (see Fig. 1.13). That is, it can be assumed that mobile genetic elements are the connecting mechanism of all discrete genomes on Earth into a single information space. With this, any mutations and recombinations of the genome of any organism can come into possession of the entire global genome system and manifest in various, difficult to predict forms of phenotypic framework. Moreover, any gene or nucleic acid segment can be transferred to any discrete part (to any genome) of the genosphere (see Fig. 14.7). Viruses have genetic links with representatives of all species of living organism. For example, even the human genome is composed of approximately 30% virus-like elements, transposons, and their residues. Thus, all living matter is united by the bioinformation streams circulating within the global genome system. The existence of a single information space and the global interconnection of all carriers of information ensure the perception of any genetic fluctuations, their transmission to any part of the genosphere, and their manifestation in some quite incredible forms. Such fluctuations of genetic information can be one of the mechanisms of evolution. That is, viruses are a natural tool for gene transfer between different

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taxa and are one of the factors of communication of genomes at the molecular level. They participate in and influence evolution, biodiversity, and population regulation. That is, the evolution of living bodies, which is manifested by qualitative and quantitative changes in the composition of the global phenome, is a secondary phenomenon. In turn, the molecular variability of genomes, which causes changes in the system of phenotypes, is the primary process of evolution. Such variability is conditioned by mutation, recombination, hybridization, and the activity of mobile genetic elements. The emerging changes can in turn be extracted, modified, and transferred to any discrete genome of a single information system using these mobile elements. That is, viruses and their analogues are special tools for the transfer of genetic information and the endless process of evolution (see Fig. 1.12). Viruses are rather mutable and constantly evolve in parallel with the development of living organisms (see Fig. 1.13). Today, many mobile genetic elements are competent representatives of all discrete genomes, cells, and organisms that live on Earth. For example, according to various sources, mammalian genomes contain from 8 to 30% of the nucleotide sequences characteristic of retroviruses and their residues. It can thus be assumed that the existence of many viruses in the form of proviruses in nucleic acids constitutes the main stage of their life cycle (their reservoir), while outside the cells they are in a transitional state of suspended animation, in the form of a kind of cyst. Fig. 1.12 Structure of the phage indicates that it is a special tool for manipulating membrane molecules and DNA. (1) Protein capsomeres, (2) head, (3) collar, (4) neck, (5) tail tube, (6) sheath, (7) base plate, (8) tail fiber. With the help of fibrils, the phage targets the surface of a bacterium. The hollow tube of the tail is inserted between the phospholipid molecules of the membrane and forms a channel through which the virus DNA is injected into the cytosol of the host cell

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Fig. 1.13 The stages of existence of viruses are the stages of transformation and transfer of information. (2, 4, 6) Stationary stage in the form of episomes in the genome of one of the hosts. (1, 3, 5, 7) Transit stage in the external environment. (1) Virus in the external environment. (2) Virus as a part of the human cell genome. (3) Mutant virus with “stolen” DNA segments of the host. (4) Virus inside the genome of chicken cells. (5) Repeatedly mutant virus containing chicken DNA segments. (6) Virus inside the genome of pig cells. (7) Repeatedly mutant virus containing DNA segments of chickens and pigs. (8) Next infection of human cells. This circulation of viruses among several genomes of different hosts allows them to deceive the defense system of organisms. A—human cells, B—chicken cells, C—pig cells

1.14.4 Are Viruses Living Organisms? As noted in Chap. 9, the ability of an individual living body to reproduce independently is not a critical characteristic of vitality. For example, mammalian erythrocytes cannot multiply, but they can live safely in the body for several months. At the same time, they are able to maintain their metabolism, and they are capable of self-recovery and the performance of their functions. That is, the inability of viruses to reproduce on their own does not mean that they are inanimate. Moreover, the absence of signs of life in virions outside cells does not prove the absence of life. There is a phenomenon known as “hidden life” (see Sect. 1.15), when the vital manifestations are completely absent in organisms under certain unfavorable conditions, but can manifest themselves in favorable ones. This is exemplified by the state of suspended animation in various microorganisms that can remain for years in a frozen or dehydrated state, then successfully come to life when the temperature rises above 0 °C and liquid water becomes available. The same goes for virions. When they enter the favorable environment of a host cell, they revive the cellularviral system of life and begin parasitic reproduction, creating copies of themselves by self-assembly.

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Note also that the fact that viruses do not have their own metabolism and selfrecovery does not prove that they are not alive. We assume that they possess a mixed metabolism. After all, what happens inside a cell infected with viruses clearly corresponds to metabolism, as the course of a succession of biochemical processes. That is, a new type of living system, which has a certain distinct type of metabolism, is created inside the affected cell. It is a mixed metabolism that belongs simultaneously and equally to both the host cell and the virus. But the most important thing is that viruses have their own genome, and are able to reproduce and transmit it to the following generation for thousands of years without losing their specificity. On this basis, they have the ability to mutate and to undergo natural selection and evolution. Based on our concept of the dual nature of the phenomenon of life (Chap. 16), it is possible, by analogy, to assert that there is a planetary system of millions of species of non-cellular living beings. Viruses are the organizing elements of this system. Just like the planetary system of life of cellular bodies, this huge heterogeneous system is extremely stable and has existed for billions of years. It continuously and actively functions, reproduces, renews, restores, and evolves. That is, it possesses all the characteristics of living systems. Non-cellular structure does not indicate the absence of life or the basic characteristics of life, such as the ability to transform matter and energy for self-recovery and reproduction. Thus, viruses are living bodies, a legitimate part of the unified planetary system of life. From our point of view, they are mobile micro-creatures living at the cytogenetic level of living bodies, making an important contribution to the modification of representatives of individual life and also to the evolution of the phenomenon of life itself. Their existence is imperceptible to human eyes, and only in the case of pathological parasitism is it possible to judge the course of molecular processes corresponding to their presence by phenotypic changes in the host. Thus, most likely, viruses are the oldest living derivatives of prokaryotic organisms that reigned on Earth during the first 1.5 billion years. Both then and now, their main purpose is the multi-vector transfer of genetic information in the system of a single information space of life.

1.15 Hidden Life The geophysical parameters of the Earth have altered in accordance with the evolution of the Solar System, leading to the development of very different environmental conditions in various places on our planet. In particular, these conditions can differ significantly in temperature and the availability of water. Life arose in water through a long process of evolution, combination, and interaction of organic molecules in a liquid medium. Almost all living organisms contain an average of 70% water. The environmental temperature conditions have to keep

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the water liquid for optimal rates of movement and interaction of molecules. Therefore, the temperature range of life lies between 0 and 90 °C. Higher temperatures irreversibly destroy DNA and proteins, which are the molecules of life. According to the laws of physics, the rate of movement and interaction of molecules decreases with falling temperature. Consequently, the metabolic rate in living systems decreases, and this is manifested in the inhibition of all functions up to the complete cessation of life processes. Significant inhibition of metabolism and cessation of life can also be observed under conditions of dehydration of organisms, since it is impossible to have sufficient movement of molecules in the absence of water and the course of biochemical processes then also becomes impossible. Thus, depending on temperature and water content, life processes can proceed at different rates, be strongly inhibited, and even reversibly terminate. As a result of billions of years of evolution, life on Earth can exist in several different states depending on the degree of manifestation under corresponding environmental conditions. 1. Biosis is the effective vital activity, in which all the properties and characteristics of living beings are exhibited: nutrition, respiration, excretion, movement, reproduction, and so on. This state of life is typical for the majority of organisms living in normal environmental conditions with body temperatures from + 5 to + 40 °C. Under these conditions, the genetic programs recorded in the genome are actively implemented, providing for all necessary processes. 2. Hypobiosis is suppressed vital activity. The lower temperature limit for life in organisms (0 °C) comes from the need for a liquid aqueous internal environment, which provides for metabolic reactions and metabolite fluxes. When they approach this limit, organisms can pass into a state of hypobiosis, which is characterized by a sharp suppression of movement, nutrition, respiration, excretion, and other signs of life. For example, it is manifested as the cold torpor of many amphibians and reptiles, and hibernation in some rodents, insectivores, and bats. The temperature of their bodies in the winter period goes down to 0 °C for quite a long time. In this state, other genetic programs of the same genome are switched on, providing the processes of adaptation and existence in other conditions. When the normal temperature is restored, these animals are reactivated and return to the previous genetic life-support programs. 3. Cryptobiosis is a hidden life. It is a state of physiological rest that is based on adaptations that contribute to survival under unfavorable environmental factors. Virtually no signs of life are manifested in the state of cryptobiosis, although a low level of metabolic processes remains. In many organisms, an active life alternates with a state of rest. Cryptobiosis includes such life forms as the spores and cysts of microorganisms, algae, and fungi; the seeds and brood buds of plants; the gametes of animals; the diapause of arthropods; and others. In this state, the genetic material is mothballed, so to speak, as virtually no information is read from DNA molecules. However, DNA molecules and many proteins can be preserved for a very long time in this condition. Owing to this phenomenon, life on Earth is preserved, develops, and even spreads, despite the presence of unfavorable

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environmental factors. The dormant state is usually preceded by preparation: the storage of nutrients, dehydration of cells and tissues, and a decrease in the metabolic rate. This is provided for by special genetic programs. 4. Anhydrobiosis is the ability to withstand deep and long-term dehydration while maintaining the ability to repeatedly restore active life after watering. This phenomenon is typical for some microorganisms, plants, and invertebrates. Unlike cryptobiosis, anhydrobiosis occurs without preliminary preparation upon rapid dehydration, and the vital activity is restored just as quickly after hydration. The water content of anhydrobionts can drop down to a mere 1–3%, which is insufficient for biochemical processes. Genetic programs are not implemented either under these conditions. Species of bacteria have been found in the salt deposits of ancient seas and lakes 260 million years old, and their dehydrated representatives were able to revive under favorable conditions. The main condition for the restoration of vital processes is the preservation of the intact structure of proteins and DNA molecules. 5. Anabiosis is a temporary reversible cessation of life under such environmental factors as deep freezing or deep dehydration. It is typical for some microorganisms, plants, and simple animals (for example, rotifers, barnacles, and tardigrades). Representatives of some species of amphibians and reptiles can endure deep freezing in the winter season for several months (“die” and then come to life again). Seeds and spores of plants, various microorganisms and bacteria, spermatozoa, erythrocytes, bone marrow cells, and so on, can be frozen in subzero temperatures up to the temperature of liquid nitrogen (–196 °C) under experimental conditions. In this state, these objects can exist for years. DNA molecules and proteins of these objects are in a cryopreserved state. Metabolism and implementation of the genetic information of the genome are absolutely absent, but after thawing, they can completely restore all vital processes. Some microorganisms can be freeze-dried and then stored at room temperature for a long time. When rehydrated, these organisms come back to life. The ability to go into anabiosis is determined by the ability to preserve the structure and functions of proteins and nucleic acids, even at nearly absolute zero temperatures and with complete dehydration. That is, in all cases, a reversible cessation of life is possible only if the structural bases of organisms are preserved. The minimal condition is to be capable of maintaining the structure of genomes, that is, the structure of DNA and proteins. Can sperm or rotifers frozen to –196 °C and showing no signs of life be considered dead or alive? Apparently, neither one nor the other. This is a kind of alternative state of existence of living bodies without signs of life. This is a state of “hidden life,” as the ability to return to full life is retained after thawing. Such systems remain viable. That is, the freezing of such living bodies can be regarded as a temporary cessation of the life process. It is a temporary suspension of the manifestations of life, while the structure and potency of the bodies and genomes are preserved.

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This means that the phenotypic life of the body is only a manifestation of the potential properties of highly organized matter. These properties, in principle, may not be expressed in the absence of necessary conditions, although highly organized matter will happily exist even in a frozen state. That is, although the material and informational bases of life are preserved, they are not necessarily manifested. Thus, this example shows that life is conditioned by the specific potential of highly organized matter, the core of which is the genome. Under conditions incompatible with the manifestations of life, for example, when frozen, living bodies do not manifest their biological properties. However, they retain high levels of organization (low entropy), as well as the structural, functional, and genetic potential for revival. The phenomenon of the temporary absence of manifestations of life testifies to the possibility of the existence of a hidden life, the stable substrates of which are dormant complexes of nucleic acids and proteins. These molecules, as the main organizers of life, can immediately manifest themselves in various processes and traits under favorable conditions. Based on the above, one can come to a paradoxical conclusion that it is not necessary to live permanently in order to exist. The possibility of intermittent vital manifestation is also one of the properties of life. That is, certain physical and chemical conditions are necessary only for the implementation of life processes and phenotypic manifestations of life, and not at all obligatory for the “silent” existence of its bodies and substrates! From this point of view, life can be in two states: (a) existence with manifestation; and (b) existence without manifestation (hidden life). By “manifesting life”, we mean the presence of living bodies that move, breathe, feed, reproduce, and undertake chemical and physical processes to maintain integrity and order. If “life does not manifest itself,” it means that the existing bodies do not move, do not breathe, do not eat, and generally do not have metabolic processes. This may be not only due to death, but also to a temporary halt in life processes. Therefore, even if there are no manifestations of life, this does not mean that it is not there. Anabiosis perfectly demonstrates the possibility of a reversible cessation of life. On the one hand, we can see living functioning bodies at physiological temperatures; on the other hand, these same bodies can exist in a frozen state for a long period of time with complete absence of vital manifestations. After rewarming, the bodies become alive again. The main question is: where is life hidden between these periods of activity?

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1.16 Summary The phenomenon of life is the process of existence and functioning of the entire set of living bodies on Earth. This is an integral phenomenon, although it is represented by an infinite number of discrete units of life, the living bodies, which are phenotypic representatives of their genomes. On the one hand, life is associated with the process of existence of living bodies with certain physical characteristics and a short individual lifespan; on the other hand, life is a natural phenomenon, an infinite system, and one of the properties of the material world. Living organisms are not something exceptional, but part of the material world. Organisms are open heterogeneous systems. They consist of many organic substances, macromolecules and organelles, strictly ordered in space and time, and whose organized interaction determines the integrity of life. Life originated, developed, and exists only on the basis of a liquid aquatic environment. It manifests itself in a very narrow range of temperatures, very close to the lowest limit possible in nature. Life became possible and still exists only on the basis of biological catalysis. To ensure the processes of reproduction, development, and maintenance of integrity and functioning, a constant supply and use of substances and energy is required. Life on Earth is proteinaceous. Bodies are composed of proteins and proteins provide catalysis. Proteins are intermediaries in the implementation of genetic information, a means and a basic element of the creation of a living body. The organization of all known forms of life is based on nucleic acids – the stem molecules of cells. These are the substrate of life, the material and informational basis of the unity of all living things. The functioning of nucleic acids in tandem with proteins in a liquid aqueous medium determines the presence of living bodies. All living beings have a cellular structure and are highly organized open systems. They are built on the basis of information, exist in a dense information environment, and also live and survive on the basis of the ability to generate, perceive, analyze, and use information. Life processes can proceed at different rates; in particular they can be strongly inhibited and reversibly cease. None of the basic features listed here is defining on its own. Only their entirety determines the possibility of the existence of the phenomenon of life.

Part II

Planetary System of Life

Chapter 2

The Unified System

We suggest that, as a global phenomenon, life consists of two inseparable components. On the one hand, life is associated with the process of existence of autonomous living bodies with certain individual characteristics, while on the other hand, life is a planetary system, consisting of the whole almost infinite number of such bodies on Earth. It is a heterogeneous but monolithic system of interdependent and interacting organisms with diverse characteristics.

2.1 Living Bodies Are the Organizers of the Planetary System of Life Millions of species of various living bodies live on our planet. They are scattered all over the Earth, forming an enormous unified system which covers its surface with a dynamic network (Fig. 1.2). Certain microorganisms (aerobionts) live in the atmosphere in droplets of atmospheric moisture, where the amounts of water and dissolved substances are sufficient for their metabolism. Solar energy serves as their energy source. Aerobionts can inhabit up to the boundaries of the troposphere, as high as 10–12 km. The geosphere is inhabited by geobionts. This is the entire colossal collection of species of terrestrial and underground organisms, from microorganisms and plants to higher animals and humans. Soil serves as their habitat. Living bodies inhabit the land surface (terrabionts), as well as the thickness of the Earth’s crust (lithobionts). The hydrosphere is the entire global water layer, covering 75% of our planet. It is inhabited by hydrobionts. Representatives of all kingdoms of living beings can be found there. The biomass of the entirety of living bodies on Earth is 550 billion tons of carbon. More than 80% of this mass belongs to plants, which make up 450 billion tons. Seventy billion tons corresponds to the weight of bacteria. Fungi make up 12 billion © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_2

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tons, archaea 7 billion, protozoa 4 billion, and animals only 2 billion tons, and the weight fraction of humans is only 0.06 billion tons. Living organisms inhabit our planet very unevenly. Their distribution depends on temperature, light, sources of nutrition, and the absence or presence of competitors. The geographic latitudes of the tropics and subtropics are most abundantly inhabited due to the stability and sufficiency of lighting, the warm temperature, and the presence of large amounts of water. The Arctic and Antarctic zones of the Earth are considerably less populated. Interestingly, the majority of plants are terrestrial species, most of the biomass of animals lives in the seas and oceans, and the majority of the bacteria and archaea inhabit the soil. Moreover, the total biomass of terrestrial organisms is about two orders of magnitude greater than that of aquatic organisms. All this diverse mass, distributed over the entire Earth in an uneven network, forms a global living system or living sphere—the “biosphere”, a community of organisms that exist on Earth and interact as a whole. The biosphere, as a planetary system of life, began to form about 3.8 billion years ago. At that period, many protozoan living organisms appeared on our planet. Over time, the living elements of the system penetrated into the upper part of the geosphere, into the entire hydrosphere, and also into the lower part of the atmosphere. This system was formed gradually over billions of years. During this time, millions of species of living beings were formed and died out. As a result of simultaneous and interdependent evolution (coevolution), this built up an interdependent community. Moreover, living organisms not only populated the Earth’s crust, but also transformed the appearance of the Earth, creating biogenic substances (soil, atmosphere, carbonates, oil, gas, etc.). Throughout organic evolution, living bodies have repeatedly passed most of the atmosphere through their organs and tissues, along with the entire volume of the world’s oceans, and an enormous mass of mineral substances. Currently, our planet is inhabited by more than 3,000,000 species of plants, animals, fungi, archaea, and bacteria, whose representatives possess individual life. Humans are also just a part of this diverse planetary system. The planetary system of life, despite some common organizational features, is fundamentally different from individual life (Table 2.1, Sect. 8.6). First of all, for the limited life of individuals, heredity is useless, evolution is not required, variability is even harmful, and there is no need for reproduction, whereas the planetary system of life cannot do without the reproduction of its component organisms, no more than it can do without variability and evolution in accordance with changing geophysical conditions, which determine its infinitude. Life as a systemic phenomenon is firmly anchored to our planet, just as the individual life of an organism is inextricably linked to a certain body. Thus, it is obvious that life as a global phenomenon consists of two complementary components. On the one hand, it is associated with the process of the existence of living bodies with certain physical characteristics; on the other hand, life is a planetary biosystem. That is, the phenomenon of life differs from the phenomenon of the existence of living bodies. This is similar, for example, to the difference between a chemical element and a substance. For instance, as an element, carbon has its own

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Table 2.1 Some common and distinctive characteristics of the two components of the phenomenon of life Individual life

Planetary system of life

Living bodies are molecular cell systems

System comprising the sum of all individual lives

Similarity

Similarity

Systemics. The planetary system consists of an Systemics. Living bodies represent an organized system of interacting molecules and organized mass of interacting living bodies cells Discreteness. Molecules and cells are the units Discreteness. Living bodies are the units of of structure and organization structure and organization Orderliness and organization into organelles, compartments, macromolecules, membranes, etc.

Orderliness and organization into populations, species, genera, etc.

Communication with the external environment Communication with the Planet and exchange and metabolism. Open systems of substances. Open system Differences

Differences

Individuals are represented by distinct unicellular or multicellular organisms

The system is represented by the totality of all living bodies on Earth

Molecules and cells are the structural units of living bodies

Individual living bodies are the structural units of the planetary system

Individuals exist (live) for a limited period, Planetary system of life has existed for billions very short in comparison with the existence of of years the planetary system All living bodies are mortal. They inevitably die

Planetary system of life is virtually immortal

The lifespan of individuals is limited genetically

The duration of the existence of the planetary system of life is not limited genetically

Homeostasis of individuals is maintained Homeostasis of the system is maintained by internal metabolic and physiological forces through self-reproduction of the elements of its constituent living bodies Living bodies have an intracellular metabolism based on selective catalysis

The planetary system of life has an internal system of food chains and symbiosis

The genome is the center of regulation and control of the system of individual life

The planetary system of life does not have a center of regulation and control. The balance is achieved through the conditions in the external environment and the relationships between organisms

A given individual is not subject to evolution

Evolution is inherent in the planetary system of life

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physical characteristics. But diamond, a substance based on carbon, is a completely different entity. It is on a completely different level with regard to the totality of its properties and characteristics. The difference between the phenomenon of life and individual life can be illustrated by the following example. Imagine the settlement of astronauts on Mars in the near future. Can we consider that the phenomenon of life has appeared on Mars? Most probably not, since the appeared organisms are not part of the environment and are unable to live under the prevailing geophysical conditions and at its expense. This would not therefore constitute a self-sustaining Martian planetary system made up of various living organisms that survive under different conditions and are complementary to the nature of this planet. This means that during the brief presence of the astronauts on Mars there was no phenomenon of life as such. There was only a temporary presence of living bodies, which are the individual representatives of the planetary system of life on Earth.

2.2 All Life Comes from Life A century and a half ago it was still believed that spontaneous generation of life was possible from inanimate objects and substances. But, despite numerous attempts by various scientists, no one ever succeeded in artificially creating even the simplest living organism. The experiments of Pasteur (1862) and his followers completely and finally refuted this possibility. Thus, it is firmly established that only living organisms are able to reproduce their own kind. This phenomenon, living things come only from other living things, was called biogenesis. Biogenesis is realized in the process of reproduction, which is an important property of living organisms. Moreover, any representative of a particular species produces exactly the similar individual (homogenesis). AIDS viruses reproduce in host cells only from genes of AIDS viruses, cholera vibrios appear from the same vibrios, fungi from fungi, plants from plants, animals from animals, birds from birds, cats from cats, and humans from humans. All organisms are almost completely identical to their parents in morphological, physiological, behavioral, and many other characteristics. Accurate reproduction of offspring is based on very conservative and stable hereditary genetic material. Each species of living organism has its own exclusive set of DNA molecules in the genome. These molecules contain a specific composition and their own combination of genes. The molecular basis for reproduction is the process of replication of DNA molecules. As a result, the duplicated hereditary material is distributed by mitosis or meiosis into daughter cells. Copies of parental organisms appear in the process of development on the basis of the realization of the hereditary information of an individual set of genes from the genome. These daughter organisms have the same set of DNA molecules and genes, the same genome, which they will again pass on to their offspring during the next reproduction cycle. Moreover, it is not only the genome that is cloned and transmitted to the next generation; the orderliness of the intracellular molecular system is also transferred along with a part

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of the dividing cell. Owing to this copying of the substrates of life, biological species (or rather, the genomes of species) of all kingdoms of organisms can exist for many hundreds of thousands and millions of years, despite the significantly shorter lifespan of individual representatives. The genesis of living bodies and emergence of the process of life as a phenomenon through long-term chemical and biochemical evolution was possible billions of years ago, when completely different physicochemical, ecological, and, most importantly, abiotic conditions existed on Earth. It has been established that even under the modern conditions on Earth, structures similar to coacervates can appear at the phase boundaries, for example, the ocean/air interface. But they have no further perspective, since they are immediately absorbed by various living organisms. Thus, the spontaneous generation of living bodies is impossible under current conditions. Meanwhile, the endless maintenance of various species of living organisms and their evolution is possible only due to the ability of the permanent genomes of individuals to replicate, which determines the processes of reproduction and exchange of living bodies and the immortality of the planetary system life.

2.3 Levels of Organization of Life Discreteness underlies the elements of the structural and functional levels of living organisms and biosystems. Each level has a higher complexity and possesses new properties and functions (Fig. 2.1). Elementary particles such as protons, neutrons, electrons, and others, in different quantities and combinations, form atoms of different elements. Atoms, depending on their combination and quantity, constitute the whole range of elements on our planet. Several of them make up the bulk of the organic world: carbon, oxygen, hydrogen, nitrogen, and phosphorus. Combining with each other in different quantities and combinations, atoms form molecules.

Fig. 2.1 Levels of complexity of biosystems. The combination and interaction of elements leads to a progressive increase in the complexity of systems, qualitative leaps in development, and the emergence of fundamentally new properties and functions. 1. Nonspecific elementary particles form specific atoms of the elements of the Universe. 2. Atoms form molecules of substances. 3. Membranes, organelles, and genomes are built from molecules. 4. A phenotypic framework is produced around the genome in the form of a cell. 5. Multicellular organisms, body parts, tissues, and organs are formed

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Molecules. All living organisms are composed of around 70% of water molecules. The rest of their content falls mainly into four groups of organic macromolecules: proteins (up to 20%), carbohydrates, nucleic acids, and fats. Energy is converted and stored in the form of the high-energy bonds of universal ATP molecules. Hereditary information is stored and realized via DNA and RNA molecules. Organelles are formed as a result of the ordered organization of cellular macromolecules. Special cellular structures are formed: mitochondria, lysosomes, ribosomes, and others. Different organelles have a specific macromolecular composition, which determines the specificity of their structure and functioning. The set of functioning organelles forms a cell. Cellular organisms. Cells are genuine living bodies, the units of life, characteristic of the organization of all species of organisms. Metabolism, homeostasis, protein biosynthesis, and the realization of hereditary information and reproduction are only possible at the cellular level. Colonies of cells with similar structures were initially formed in the process of evolution, and then the groups of cells acquired specialization and became tissues of multicellular organisms. Tissues. A set of cells with the same type of organization forms a tissue. Hundreds of different types of cells compose the bodies of multicellular organisms. Numerous animal cells form four types of tissue: nervous, connective, epithelial, and muscular. Organs. Organs are complex organized parts of the body, located in defined places and performing specialized functions. They form gradually in the process of development. In the vast majority of cases, an organ is formed from several different types of tissue. Higher animals have many organs of various sizes and structures that perform diverse functions. Organ systems. An organ system is a group of different organs that collectively function to perform a common task for the body. In the classical case, the organs that make up the organ system are structurally interconnected with each other and specialized to work within the framework of that particular system. These are the anatomical systems: locomotor, digestive, respiratory, cardiovascular, nervous, excretory, and reproductive. At the same time, there are other systems, physiological systems, which have only functional unity, while their organs combine fundamentally different functions as a rule. Such are the endocrine, immune, hematopoietic, and lymphatic systems, as well as numerous purely metabolic “systems without organs”, like the reticuloendothelial, renin-angiotensin, and hemostatic systems, and so on. Multicellular organisms. Interconnected functioning cells, tissues, organs, and organ systems form a multicellular living body. This is an organism that is a unit and carrier of a higher level of organization of living matter. All of the mentioned levels of organization, viz., molecular, cellular, organ, and others, work collectively (and are coordinated by the nervous, endocrine, and immune systems) for the survival of an individual organism. Hence, a multicellular organism is a supersystem consisting of numerous molecules, organelles, cells, tissues, organs, and body parts. Population level. Organisms similar in morphology, physiology, and metabolic characteristics, capable of mating and reproducing their own kind, constitute a classical biological species. This is a very successful and widespread form of existence of living organisms, but it is not the only one. Millions of bacteria and protists,

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incapable of sexual reproduction, form “clonal species”. Their individuals are incapable of mating, and reproduce their own kind only asexually. Certain groups of organisms have much more complex ways of reproducing similar individuals: the so-called “species complexes”. These are associations of several species, the individuals of which, under certain conditions, are able to interbreed with each other. Such phenomena have been discovered in the world of protists, fungi, and even vertebrates (fish, frogs). Several million different species of animals, plants, fungi, protozoa, and prokaryotes live on Earth. Within each species, there are groups of organisms with some distinct morphological or physiological peculiarities. Such groups of individuals form populations. Ecosystems are historically established stable communities of populations of different species on Earth, connected with each other and with the surrounding inanimate nature by the exchange of substances, energy, and information. They are large mixed systems with circulating substances and energy. Biosphere. The totality of ecosystems forms the biosphere. The biosphere is the “shell” of our planet, containing the totality of all life. It is all organisms that live in close connection with inanimate nature in the atmosphere, hydrosphere, and lithosphere. That is, the biosphere is a part of the common nature of the Earth. To the classical ideas on the levels of organization of life, we can also add our concepts of individual life and the planetary system of life, which are integral parts of the phenomenon of life. Of all the listed biological systems, only the cells and multicellular organisms should be considered truly alive. They are fundamentally different from other biosystems in their ability to be born and die, and only they are the real masters of genomes. The principles of discreteness, orderliness, and integrity are the backbone of all levels of organization of life. They are related not only to structure, but also to function. In particular, the metabolism of any cell is discrete, since it consists of tens of thousands of biochemical reactions; at the same time, it is integral, since it serves a single purpose of maintaining homeostasis. All metabolic reactions are strictly organized and ordered in space and time. Each reaction proceeds at a certain site within the cell and is carried out in a strictly defined order and at a strictly defined time. The organization of discrete processes is provided by selective catalysis of only what is required for the cell reactions. Selective catalysis is based on the presence of only the necessary enzymes, these being synthesized by the cell on the basis of the genetic programs of the DNA. Many substrates and products of enzymatic reactions are regulators that switch on or switch off, activating or inhibiting biochemical processes. That is, self-regulation is carried out on the basis of the internal determination and conditionality of the appearance of certain molecules (certain information). The need for their presence, as well as their effective concentration, is again controlled by enzymes, as specific derivatives of a particular genome of the whole organism. Energy is also converted and used in living systems in an organized, discrete and purposeful manner. It is selectively directed to supply only the necessary reactions and processes (see Chap. 7). Organization, discreteness, and selectivity are also

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characteristic of specific processes of the perception and use of biological information (see Chap. 13). The levels of organization of all aspects of life are built up on the basis of discreteness according to the principle of hierarchy: the lower levels of organization are necessarily an integral part of the higher levels and determine their qualitatively new properties. There is an analogy with a discrete scale of sizes and masses, discreteness in the structure of atoms, discrete energy levels in quantum mechanics, etc. That is, discreteness is one of the main characteristics of Nature.

2.4 Self-organization and Emergent Properties of Living Systems Biological objects are multi-heterogeneous, but at the same time highly organized nonequilibrium dynamic open systems (see Sect. 1.10). Self-organization processes in open dynamical systems are studied by synergetics, which relies on physical and mathematical methods, aiming to establish and generalize the patterns of the emergence and development of organized structures. This approach focuses on the study of stable states and mechanisms involved in emergence and restructuring. The basic concepts of synergetics are fluctuations and bifurcations. Fluctuation is the variation of the system or its elements with deviations from the mean values. Bifurcation is a certain critical threshold point in the fluctuations where the system is in two states at the same time. If the system hits the bifurcation point, then a qualitative change can occur in its state and performance. Under such conditions, the fluctuation can abruptly increase, making the further behavior of the system indeterminate: either it returns to its original state, or a qualitatively new state of the system arises. It has been found that fluctuations and bifurcations in chaotic disordered nonequilibrium systems can lead to the appearance of organized ordered structures with emergent properties. These are distinct properties of a system that are not inherent in its elements. An ordered structure is as an object, a system, or part of a system that possesses stability and firm connections, with the ability to resist both external and internal disturbing factors. Examples are a regular solid crystal lattice of atoms or an irregular but complex structure of a living organism that consists of various ordered elements. In contrast to orderliness, chaos is characterized by internal homogeneity and the absence of regularly located stable structures and connections between them. However, chaos can actually also have a certain kind of structure. It turns out that even the global chaotic meteorological processes in the atmosphere can be described mathematically using nonlinear equations and computer calculations. Physical and mathematical methods have shown that the formation of various structures is indeed possible in open, moving, nonequilibrium chaotic systems. Therefore, we can talk about certain degrees of order in this or that chaotic system, or the degree of disorder of this or that structure. In chemistry, for example, we have the Belousov–Zhabotinsky (BZ) reactions, where, in the presence of a specific catalyst in a citric acid solution,

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redox processes self-organize spontaneously in a certain sequence and the solution spontaneously and periodically changes its color. A chaotic system is defined in mathematics as deterministic rather than random. But even if the parameters of all elements of the system are known, we will not be able to unambiguously predict the course of its development due to the fact that the elements interact in a complex way and constantly change these parameters. Even systems with a small number of constituent elements can behave unpredictably and nonlinearly, if the principle of reflexivity is implemented. This is when one event sets the starting conditions for a whole cascade of other events, as a result of which an insignificant event can have immense consequences. The formation of membrane-like structures when phospholipids are added to an aqueous medium is an example of self-organization in organic chaotic systems. In a similar way, membranes and their derivatives are formed in cells. “Acellular systems” are an example of the self-organization of biological processes. These cell-free systems can be generated by homogenization (destruction) and fractionation of cells of various tissues. The resulting fractions (nuclei, mitochondria, lysosomes, ribosomes, etc.) can then be placed in physiological solutions, where isolated molecular systems are capable of performing their biological functions. That is, even in the absence of a cell as an organizing backbone, many processes can proceed independently and in an ordered way. Here, the centers of the organization are enzymes and macromolecular complexes. For example, the presence of ribosomes in a test tube is a prerequisite for the biosynthesis of highly organized polypeptides outside the cell. Naturally, for this process to occur, the presence of amino acids, GTP, and a number of other factors of biosynthesis is also essential. When these conditions are available, the process occurs spontaneously, automatically, and in an orderly and organized manner. It will continue as long as there are enough substrates and factors in the test tube for the self-organizing process to take place. The simplest self-organizing system of biomolecules is the presence of interacting enzymes and their substrates in a cell-free environment. Self-organization of the process of converting certain substances (substrates) specifically into others (products) occurs when their concentration is sufficient. Apparently, such self-organizing conversions are very important for the existence of cells. Spontaneous automation of myocardial contraction is an example of a selforganizing process at the organ level. The origin of the rhythmic contraction of the heart is not external, but internal forces, namely the rhythmic spontaneous formation of an electrical potential on the membranes of pacemaker cells and its spread throughout the heart. The electrical potential self-organizes as a result of the movement of anions and cations (fluctuations) through the biomembranes of pacemaker cells. At a certain moment, a critical concentration of molecules occurs on different sides of the membrane (bifurcation), and this causes an electrical breakdown of the membrane and the generation of an electrical pulse. Along with the processes of self-organization of structures, the processes of their degradation are also involved in the dynamics of various open systems. Thus, systems can be generally organized and ordered, but at the same time nonequilibrium and collapsing. Such systems and structures are said to be dissipative. They can exist

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for some time, but only through the attraction of matter and free energy from the surrounding space. Cells and multicellular organisms belong to this type of system. Dissipative systems exist far from equilibrium and enable the transition to “organized chaos” (see Fig. 2.2). Unpredictable, that is, random, but organized processes and structures arise. Such chaos is said to be dynamic or deterministic. Determination is manifested in the fact that disturbances in the system necessarily arise, whereas chaos manifests itself in the unpredictability of the locations and times of occurrence of these disturbances. The dynamism of chaos can be perceived as fluctuations of particles or objects under conditions of chaotic motion. Thus, the deterministic and dynamic chaos of the Earth’s surface 3.5 billion years ago could actually cause the emergence of organized processes and structures of different composition, size, properties, and time of existence at a multitude of points within its infinite volume. The “filter” of natural selection left the most stable systems, in which the forces of internal connections were stronger than the forces of external impacts. Then, over hundreds of millions of years, these islands of order would have evolved in an ocean of chaos. Protobionts could have appeared in this way (see Chap. 8). That is, numerous bifurcation states could have arisen on the basis of fluctuations, when the resulting subsystems passed into a qualitatively new state. This property, the appearance of new properties in dynamical systems, is called emergence. Emergent properties are among the main virtues of living bodies. It is the source of many paths of development and evolution. Self-organizing dynamical systems are nonlinear and unpredictable. It is virtually impossible to predict either the qualitative or the quantitative parameters of a possible event, or the place, or the probability of its occurrence. This means that events

Fig. 2.2 Dynamic dissipative systems create stable self-organized structures while in a nonequilibrium state. Dissipation can lead to order. The global flow of chaotic destruction of the material world and an increase in entropy spontaneously create foci of self-organization. Ordered states can arise spontaneously at bifurcation points, without violating the second law of thermodynamics. At the same time, the total entropy of the system continues to grow. But its growth does not mean a uniform increase in disorder throughout the system. Order and disorder are created simultaneously in living bodies

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developing in a chaotic system are random (unlikely). A cell, where the processes of thermal destruction are constantly under way, can be considered as a dissipative, but constantly self-organizing system via the processes of metabolism and autopoiesis. It would be impossible to foresee which of the billions of possible chemical reactions will occur or indeed where they will occur. But the general course of metabolism is due to the presence of organized structures and enzymes that selectively catalyze only the necessary biochemical reactions. Thus, the probability of the occurrence of the specific processes necessary for the cell increases significantly. The improbable becomes probable, the unstable becomes stable. Spontaneous processes of dissipation are capable of performing work on selforganization (see Fig. 2.2). “Destruction ↔ creation”: this is precisely the dual nature of the vital force of movement. This is probably the thermodynamic mechanism of life, when an uncontrollable flow of energy of destruction sets in motion a flow of matter and energy, controlled by the genome and aimed at creation and functioning. That is, it is precisely the spontaneous processes of destruction of organized biosystems that are the source of the life force and the basis for bio-creation! The paradox is that it is destruction that is both the trigger and the power of creation! The mechanism of spontaneous destruction of biosystems is also of great importance for the development and evolution of life. Due to this, no expenditure of matter, energy, or information is required at all from Nature to eliminate the old and unnecessary, since all organized systems are destroyed spontaneously. And energy, matter, and information are used only at the stage of controlled creation. The stability of dynamic systems is maintained due to balancing negative feedbacks, when a change in any parameter turns on the mechanisms of its restoration. For example, an excess of products of a biochemical reaction immediately stops the work of the enzyme responsible for the production. In contrast, positive feedbacks can enhance the changes in parameters and contribute to the emergence of new properties in the system. Various factors influence the organizing moment in dissipative systems. Factors that influence developing dynamical systems are called attractors. In Nature, these are various forces arising from natural processes such as heating, cooling, wind, lightning, all kinds of vibrations, radiation, and so on. In biology, these can be any external and internal factors affecting macromolecules (DNA, RNA, and proteins), membranes and organelles, cells, and the body. These can be physical, chemical, biological, and informational factors. Considering their huge number and strength, combinations of influences, and many possible points of application, it is obvious that the evolution of biosystems can be directed along an infinite number of possible paths. This is exactly what happened in the early stages of biological evolution. Moreover, in accordance with the theory of Ilya Prigogine, dissipative structures not only support themselves in a stable nonequilibrium state, but can even develop under conditions of increasing flows of matter and energy. The mechanisms of natural selection have secured the most stable and thermodynamically beneficial organic systems. Their further evolution led to the emergence of living bodies with the key characteristics of dissipative systems: the ability to self-recover, self-organize, and develop.

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High levels of order in living organisms are maintained by evolutionarily developed defense mechanisms acting against the action of unwanted internal and external factors. In particular, the processes of self-recovery, selective catalysis, and selective degradation are provided for by the constant consumption of free energy in the external environment and its transformation. On the other hand, a small set of chemical attractors is used by organisms to exert profound and targeted effects on various biological systems. For example, there are several dozen hormones, several neurotransmitters, unique ATP, cAMP, acetyl CoA, and some other influencing factors. Structures, which in the process of their development, as well as self-organization and evolution of the system, become preferable to others, can also be attractors. This explains the conditioning and directionality of the processes of embryonic development, when the structures that are formed have an impact on their surroundings, determining their development in a certain direction (embryonic induction). Chaos in evolution is characteristic of most physical, chemical, biological, and social systems, and development itself has a probabilistic pattern. That is, many completely unpredictable phenomena are possible in nature. There is, so to speak, a presumption of the permissibility of what is not prohibited by the laws of Nature. If something is possible in Nature, then sooner or later it may happen. Such states arise due to the fact that nonlinear systems can evolve in different manners, selecting different paths of development. Thus, the directions of evolutionary processes in biological systems are probabilistic. Over billions of years, they have evolved chaotically and randomly. The directions of evolution and the emergence of various living organisms were also determined by the random actions of certain attractors, various environmental conditions, and later by nucleic acids: first RNA, then DNA. DNA has become and is now a superattractor, capable of exerting a dramatic effect on the structuring of the surrounding chaotic material space. But the DNA molecule itself also appeared spontaneously and is subject to the random influences of various factors, acquiring random mutations, which are in turn selected by environmental conditions. Thus, millions of species of living organisms living on Earth have random genotypes and phenotypes. Moreover, both now and in the future, they will evolve randomly and unpredictably. In a possible repetition of the evolution of living organisms, the process would proceed in a completely different, absolutely unpredictable way, but it would proceed! This allows us to consider that life is not just a phenomenon of the existence of certain autonomous organisms and species, but a continuous process of evolution of limitless “networks” of genomes and phenomes in the developing world. DNA molecules and their combinations in genomes (chosen by natural selection), depending on the accumulated genetic information, are able to lead the processes of organization in a certain direction, forming a structured material space around them that ensures their survival and reproduction. In the end, this structured space becomes a certain organism, forming a phenome around the genome. It is the phenotypic manifestations of life in the form of separate living bodies that we see around us and perceive as factual life. But within the framework of hundreds of millions of years of evolution, these are just the temporary transitory forms of the existence of the constantly evolving genomes that determine the phenomenon of life. The direction

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and purpose of this development is uncertain, random, and unpredictable. This is just one of the forms of existence and development of matter, which is not fully understood by us. The model systems that scientists use to describe the surrounding world contain elements of both order and disorder. In this sense, the model of dynamic chaos is a link connecting completely deterministic systems and fundamentally random ones. Based on this, it is obvious that chaos at the micro level can lead to orderliness of systems at the macro level. For example, the chaotic motions of molecules in the cytoplasm of cells is the basis for ordered cellular metabolism. That is, in many biological systems, order is inseparable from chaos, and chaos itself acts as a super-complex ordering. Moreover, with increasing orderliness, the possibility of system development decreases. For example, embryonic and stem cells are the least differentiated (least ordered), while capable of developing into dozens of other cell types. Conversely, highly ordered differentiated cells (neurons, myocytes, etc.) are virtually incapable of development. Thus, chaos with its dynamic instabilities is the driving force and potential for self-organization of the system in the process of its development. What picks out one of the many ways and directions of self-organization? It is known that, at nonequilibrium phase transitions, that is, at bifurcation points through which the process of self-organization is carried out, the system follows the path corresponding to the lowest production of entropy. This means that in the process of evolution of living systems, the direction of their development will be determined by the emergence of structures with the greatest order under the given conditions. It is possible to say that, in a sense, biosystems structure the energy from the external environment. Its ordered part remains in the system, and the system returns the disordered part back to Nature. The ability to self-organize is inherent not only in structures, but also in processes. In particular, the well-known theory of hypercycles postulates the spontaneous formation of self-sustaining non-equilibrium networks of enzymatic reactions, their development through the feedback system, and the formation of new forms of organization. The property of self-organization is inherent in all systems, regardless of their physical nature and structural peculiarities. Organic or inorganic, ordered, equilibrium or non-equilibrium systems can be created. Thus, randomness and irregularity can create an order that is fundamentally different from the ordering of equilibrium systems. Nonequilibrium ordered systems (for example, a cell) exist only under the condition of constant exchange (matter, energy, and information) with the environment, and equilibrium (for example, a crystal) without the exchange. Hence, one of the properties of the chaotic developing material world is its ability to generate centers of self-organization. This explains the emergence of complex structures and processes from the simple ones, a whole from its parts, all together possessing the emergent property of life. Realization of the possibility of selforganization allows understanding the roots and mechanisms of origin of phenomena, and to consider life as one of the natural manifestations of the properties of nature.

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2.5 The Illusion of Diversity Currently, several million species of various living organisms live on the Earth simultaneously, and more species are being discovered daily. Living organisms are incredibly diverse in their organization, functions, metabolism, motility, habitats, etc. These can be extremely small, simply arranged viruses, bacteria and unicellular organisms, or all kinds of highly organized multicellular plants, various fungi, and numerous animal species. Organisms also differ in the units from which they are formed: the cells of plants, fungi, animals, and bacteria have differences in structure, properties, and functions. Notable differences are also associated with peculiarities in the way the genome is organized. To date, there are two fundamentally different approaches to the classification of living organisms: the traditional ecomorphological (phenotypic) approach and relatively new phylogenetic (genotypic) approach (see Fig. 2.3). The first is based on the study of the similarity between creatures in terms of anatomical, physiological, biochemical, and other parameters of the phenotype. The second is based on the clarification of family relations between organisms by analyzing their nucleic acid structure. The classifications based on these two approaches differ significantly, since unrelated organisms can have a similar structure and vice versa. Currently, the phylogenetic approach prevails in taxonomy, while specialists from some other areas of biology prefer to use the ecomorphological approach, as more traditional and convenient in practice. Phylogenetic classification based on the genetic code is unifying, as it testifies to the unity of living beings, while ecomorphological classification is dissociative, creating the illusion of insurmountable boundaries between life forms, such as animals and plants. Let us now take a look at the phylogenetic system, offered by Sina Adl et al., which includes three domains: Bacteria, Archaea and Eukaryotes. Eukaryotes include 10 kingdoms: Metamonads, Discobas, Rhizaria, Chromists, Alveolyates, Cryptophyceae, Amebozoa, Plants, Fungi and Animals. All the kingdoms of Eukaryotes, except for the last three, are united in the formal group of Protist. DOMAIN ARCHAEA. Representatives of this domain are the most ancient cellular organisms currently living on our planet. They emerged on Earth about 3.8 billion years ago. They are exclusively unicellular creatures that do not have a nucleus or two-membrane organelles. Therefore, they have long been considered as bacteria. It has now been proven that these creatures are equidistant from both bacteria and eukaryotes, and are a unique fragment of the relict microworld that inhabited the Earth 2–3 billion years ago. Archaeal membranes are formed not by phospholipids, as in bacteria and eukaryotes, but by polyhydric alcohols, sometimes arranged in a monolayer. Many archaea are capable of photosynthesis, but they lack chlorophylls and bacteriochlorophylls; their photosynthetic pigment is bacteriorhodopsin. Only archaea are capable of photoheterotrophy, i.e., use solar energy for the catabolic breakdown of foreign organic matter. In contrast to bacteria, the archaean genome contains introns (this is one of the pieces of evidence that eukaryotes are descended

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Cyanobacteria Actinobacteria

Chromists

Plants

Animalia

Alveolata Fungi

Proteobacteria Chlamydia

Rhizaria

Spirocheta

Discobas

Cryptophyceae Amoebozoa

Metamonads

Bacteria

Archaea

Eukaryota

Fig. 2.3 Phylogenetic tree of life based on the data of rRNA gene sequencing. These are among the most ancient genomes; they have existed in all living organisms for more than 3.5 billion years. According to this system, life began from a single common ancestor, and all living organisms are related to each other, despite their different levels of development, size, and shape

from archaea and not from bacteria). Their ribosomes are similar in size to eubacterial ribosomes, and in shape to eukaryotic ribosomes. Archaea are also characterized by the absence of an electron transport chain, and the proton gradient is generated using the so-called bacteriorhodopsin proton pump. A unique feature of some archaea is also a complex of enzymes for methanogenesis. Neither eukaryotes nor bacteria are capable of producing methane. Most archaea are extremophiles: they have retained adaptations to the conditions that prevailed on the planet billions of years ago! Hot springs are home to thermophilic archaea that are resistant to temperatures from + 45 to + 113 °C; archaea psychrophiles are capable of reproduction at relatively low temperatures (– 10 to + 15 °C); archaea acidophiles live in acidic environments (pH 1–4); alkaliphiles, on the other hand, prefer alkalis (pH 9–11). Barrophilic archaea can withstand pressures up to 700 atmospheres, while halophilic archaea live in hypertonic salt solutions with NaCl contents of 25–30%. DOMAIN BACTERIA. This brings together a wide variety of species of freeliving, simply arranged unicellular and colonial organisms that do not have a nucleus, two-membrane organelles, or cytoskeleton. Their genetic material is represented by one circular DNA molecule (without histones), which moves freely in the cytoplasm, as well as by numerous plasmids. Cytoplasmic organelles are represented by 70S ribosomes, mesosomes, thylakoids, and various vesicles. Bacteria are very small organisms (0.3–30 μm) of various shapes: round (cocci), spiral (pale spirochete), rod-shaped (tubercle bacillus), etc. Many are surrounded by a dense membrane;

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some have flagella that are fundamentally different from the flagella of eukaryotes. Bacteria have mastered all the major ways of obtaining nutrition. They are capable of both oxygenic and anoxygenic photosynthesis (i.e., during photosynthesis they may or may not emit oxygen), and they are capable of synthesizing organic substances from inorganic ones, using the energy of oxidation of minerals (nitrogen, sulfur, iron, manganese). Finally, they are also capable of heterotrophic nutrition, albeit without phagocytosis. Representatives of bacteria are extremely widespread on our planet. Just like viruses, they spread through the entire biosphere: from kilometers deep in the Earth’s crust or ocean to the uppermost layers of the atmosphere. Together with protozoa, prokaryotes make up 50% of the biomass on Earth. Some types of bacteria are pathogenic and cause infectious diseases in animals, for example, tuberculosis, syphilis, pneumonia, gangrene, etc. It was bacteria, together with archaea, that created a fully-fledged biosphere of the modern geochemical type about 3 billion years ago. Eukaryotes and multicellular organisms simply entered the prokaryotic biosphere, adopting it as their habitat for all subsequent stages of evolution. And now the rest of the living world cannot exist independently, without microorganisms, which remain the basis for the support system of planetary life. DOMAIN EUKARYOTA. This is a very diverse group of living organisms that appeared on Earth about 2 billion years ago. They live in all biotopes of our planet, with the exception of anaerobic zones. Representatives of this domain can be unicellular, colonial, and multicellular organisms with highly differentiated cells, tissues, and organs. Their cells contain a nucleus, and their genome contains histones. The cytoplasm of eukaryotes contains a variety of membrane organelles that form a system of internal membranes. Most species have mitochondria; autotrophs have chloroplasts. Biomembranes are bilayered and consist of phospholipids and proteins. Protista. The largest and most diverse part of the eukaryote world, this group of kingdoms is a collection of several hundred (!) genealogical branches of the tree of life, which, with rare exceptions, have not mastered true multicellularity. Protists are not related to each other, so phylogenetic systematics does not recognize them as a single group, but divides them into several groups. At the same time, protists can be considered as a single level of organization characteristic of the early stages of the evolution of the eukaryotic world. The sizes of protists are usually in the range from several tens of micrometers to several millimeters. However, individual “record holders” can reach gigantic values: myxomycetes up to 1–5 m, and brown algae up to 35–70 m. Protists have a very broad set of intracellular organelles, thousands of different enzymes, and a rather complex metabolism. Many special purpose organelles are characteristic only of protists: ejectosomes, pyrenoids, stigmas, axostiles, parabasal bodies, etc. Some protists (foramenifera, diatoms, and sinurids) are enclosed in an external skeleton, or, on the contrary, have an axial endoskeleton (radiolarians, silicoflagellates). The composition of the skeletons is also diverse. These can be silicates, calcium, magnesium, and even strontium salts. Protozoa are very widespread. They live in the aquatic environment, in soil, and in living organisms, but only very few of them are able to live directly in the terrestrial air environment.

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Outside the formal group of protist kingdoms, there are three “classical” kingdoms of eukaryotes, most of which have a complex multicellular structure: plants, fungi, and animals. Plantae Kingdom (Plants). This is one of the largest kingdoms, including over 300,000 species of unicellular, colonial, and multicellular organisms, whose cells are capable of oxygenic photosynthesis. Such cells absorb light photons and convert their energy into the energy of the chemical bonds in ATP molecules, which is further used for the synthesis of primary organic compounds using CO2 and H2 O from the environment. Currently, only the organisms containing chlorophyll b (green algae and vascular plants) are unconditionally classified as plants; all other photosynthetic eukaryotes are considered as part of the diverse world of protists. Plants are characterized by the presence of two-membrane chloroplasts (photosynthetic protists may have 1, 3, 4, or 5 membranes) and a cellulose cell wall (protists may not have it, or it contains β-1,3-glycan, β-1,4-glycan, protein, and minerals). Vascular plants do not have centrioles, but green algae do. Plants have the highest biosynthetic potential in the organic world and also possess a secondary metabolism. They are widespread in both aquatic and dry-air environments, and, unlike protists, plants have mastered homoiohydry, that is, the ability to regulate the water content in their body. Plants have a rich system of symbiosis with other organisms: bacteria (nodule nitrogen fixation), fungi (lichen, mycorrhiza), and animals (pollination and seed dispersal). Higher plants have a complex organ-tissue structure. Mycota Kingdom (Fungi). This is a large group of eukaryotes, with over 50,000 species currently described. However, it is estimated that their number is at least six times greater. These are relatively simple unicellular and multicellular organisms, which possess an osmotrophic type of feeding: they absorb nutrients with their entire surface (like plants), but are unable to synthesize organic substances from inorganic ones (like animals). The cells of fungi contain most of the conventional eukaryotic organelles (except for plastids), as well as a number of specific ones: symplechosomes, colacosomes, and others. The cell walls of fungi contain chitin and β-1,3-glycan. The reserve polysaccharide of fungi is glycogen, and urea is present in metabolic products. The exquisite enzyme apparatus of the fungal cell is capable of breaking down lignin, keratin, and cellulose. They can break down and assimilate even glass, rubber, and plastic. The size of the genome in fungi is the smallest among eukaryotes. This is due to the fact that multinucleation allows these organisms to avoid the accumulation of reserve repeats in the genome. Most often, the bodies of fungi are represented by the mycelium, which consists of thin branching filaments (hyphae). Fungi reproduce with the help of a variety of small single and multicellular structures, which have the collective name “spores”. Fungi have mastered all habitats, and are found in the depths of the sea, in the soil, and throughout the terrestrial environment; a huge number of fungi are parasites of animals, plants, and even other fungi. This kingdom is classified into higher and lower fungi. The hyphae of lower fungi do not have a multicellular structure and are saccular or branched cells with

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numerous nuclei; they reproduce by means of zoospores. The hyphae of higher fungi have septa that separate them into pseudo cells; these organisms reproduce with immobile spores. The mycelia of higher cap fungi is located in the thickness of the substrate (soil, wood, tissue of the host organism), and various sporulation organs, including fruit bodies, are formed on the surface. Metazoa Kingdom (Animalia). This is the largest group of eukaryotes, represented by 7.7 million known species of multicellular organisms, as well as several groups of their unicellular ancestors, such as choanoflagellates, mesomycetozoea, filasterea, and others. Animals possess a phagoheterotrophic type of feeding: they are able to absorb organic matter from the surrounding space by ingestion. Most of them are mobile and have limited growth; the end product of protein metabolism is urea, and occasionally ammonia or uric acid. Animal cells have a limited set of organelles. They do not have rigid walls, so are elastic and mobile; there are also no plastids, vacuoles, or mineral inclusions. Animals have the most advanced organ-tissue structure: only they have organ systems, including specialized regulatory systems—nervous, endocrine, and immune. They are characterized by the most complex behavioral reactions, and in contrast to other organisms, these reactions are structurally determined (due to the presence of neural networks). Animals have a colossal variety of specialized cells that perform distinct functions. They possess the most complex genetic apparatus, with dozens of chromosomes. Numerous animal phyla are distinguished on the basis of structural features and vital activity. For example, coelenterates, worms, mollusks, arthropods, and chordates. Each phylum contains thousands of different animal species. The “non-cellular” part of the organic world is represented by the enormous variety of viruses (see Sect. 1.14). Viruses are one of the most widespread forms of organic matter on the planet. For example, the waters of the world’s oceans contain a enormous number of bacteriophages—about 250 million particles per milliliter of water. Hundreds of thousands of virus species live there, the vast majority of which have not been studied. Viruses are tiny bodies made up of one DNA or RNA molecule, several enzyme molecules, and an envelope. The genomes of viruses are represented by a nucleocapsid containing nucleic acids and several kinds of protein (Fig. 1.12). Virions vary significantly in structure, organization, DNA or RNA content, host and site of parasitism, method of reproduction, and distribution. They have many kinds of shape: rod-shaped, spherical, oval, etc. They are extremely small: 15–300 nm and do not have their own metabolism. All viruses are intracellular parasites. Some of them cause diseases in animals, fungi, plants, and even bacteria (bacteriophages). They are ubiquitous, but outside cells they do not exhibit the properties of living beings. Viruses are highly resistant to many adverse environmental factors. They are capable of mutation, which means variability, adaptation, and evolution. They have the same nucleic-protein nature as other living organisms. They are the universal carriers of genetic information within the global genome and the representatives of genotypic life. Thus, the aggregate of trillions of different living bodies described above forms a huge planetary system of life, covering the entire Earth. It should be noted that during the existence of this system (approximately 3.5 billion years), many millions of other,

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highly diverse species of living beings have lived on our planet, as evidenced by their numerous fossils. All of them had exactly the same “nucleic-protein” principles of organization and function as modern organisms. Any organism living now is derived from the organisms that lived before. Each is a link in an endless ramified chain that stretches through billions of years to the moment when life processes first became associated with organized systems of matter. And this chain is rapidly continuing to develop towards a difficult to imagine and unpredictable future. Earth, and then life, began a joint process of continuous change several billion years ago, and this process continues today. The reproduction of the first cells and their derivatives formed an uninterrupted chain of living organisms, transmitting to their descendants the structures and processes of the living state of matter. Colonies of new cells were formed from certain types of individual cell, which were characterized by properties inherent in animals or plants. After many millions of years, these colonies gave rise to countless living organisms, the properties of which were determined by adaptation to their environment. This led to the emergence of different organisms almost everywhere on our planet, provided that the conditions corresponded to the existence of aqueous solutions of nucleic acids and proteins. Moreover, since life is a continuing process of constant development, it represents not only millions of species currently living on Earth, but also billions of those that lived before. However, despite the colossal visual diversity, all living organisms had and have much in common in their organization and principles of functioning. In particular, all organisms are constructed from cells (except viruses). All cells have a genome, a cytoplasmic membrane, similar organelles, similar genetic material, a single mechanism for the realization of genetic information, the same laws of heredity and variability, and many very similar biochemical processes. All cells and organisms convert energy, synthesize many identical substances, and maintain internal homeostasis. The cells of all organisms have a similar molecular composition and metabolic mechanisms. Metabolism and functions are carried out on the principles of catalysis. All have similar principles of reproduction, development, and much more. That is, life is the sum of structures and processes that are fundamentally the same (and equivalently organized) for all living bodies. Depending on the species of organism, structures and mechanisms can vary, providing a diversity of living bodies. But in all cases, the dominant structure that provides for all aspects of life is the genome. This unity in diversity testifies to the identity of life in all its manifestations, to the single source of its origin, as well as to its gradual complication as a result of the process of progressive evolution. Thus, the visual ecomorphological diversity of living bodies is an illusion that hides the true integrity and unity of life.

2.6 Genomes, Phenomes, and the Planetary System of Life The main organizational similarity of all living bodies is that any organism is a unity of genotype and phenotype. Taking these concepts into account, we can assert that

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organisms represent both a genetic program (genome) and its final “product” in the form of a certain body (phenome). From our point of view, the genome is first and foremost an intricate material complex, rather than just a collection of genetic material and information. This is the most important part of a cell, containing a special, strictly ordered set of nucleic acids, proteins, and other structural and functional complexes, organized into a single colloidal system. This system contains not only the genetic information, which is necessary for the construction, functioning, and reproduction of this kind of organism, but also the mechanisms and tools for its implementation. The genome is a whole entity, capable of manipulating matter and information, reproducing, and building a phenome around itself (see Fig. 2.4). The countless variety of DNA and RNA molecules existing in nature contains an abyss of genetic information. Functioning individually or in various combinations, they form many different variants of genomes, which order the surrounding material space by means of the associated protein molecules, creating specific phenomes in the form of individual representatives of species of living organisms.

Fig. 2.4 Genome of a cell and its surrounding phenotypic framework in the form of the cytoplasm and surface apparatus. a—A cell. b—Scheme of organization of a genome in a phenotypic framework. The genome is mainly concentrated in the nucleus and has a phenotypic framework (surface apparatus and cytoplasm) that separates it from the unstable external environment. The phenome is an active mediator between the genome and the external environment. The surface apparatus and the contents of a cell absorb adverse impacts and signals from the external environment, participate in metabolism, and maintain the homeostasis of the genome

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Table 2.2 Conditional classification of different genomes based on genetic material Type of genome

Genome characterization

Genome of prokaryotes

The genome of prokaryotes is represented by a nucleoid—a single circular DNA molecule, as well as plasmids capable of independent replication

Genome of eukaryotes

The genome of eukaryotes contains several DNA molecules organized in linear chromosomes located in a cell nucleus. Additional genetic material is contained in mitochondria and plastids

– Unicellular organisms

The genome of cells is represented by chromosomes located in the nucleus

– Multicellular organisms

The aggregate genome of a multicellular organism consists of the entire multitude of variously differentiated genomes of all cells that maintain the integrity and functionality of this organism

Genome of a biological species The genome of a species is represented by a specific karyotype. It determines the individual characteristics of representatives of this species and is directly involved in the processes of self-reproduction Genomes of taxa

The genomes of taxa consist of the sum of the genomes of taxonomic units. They determine the fundamental differences between large groups of living bodies

Global genome

The global genome consists of the whole variety of genomes of all living bodies on the planet

The following classification of genomes of living systems can be proposed using the taxonomic classification of living organisms and the structure of living bodies (Table 2.2). Thus, the entire information set of genomes of all the taxa of living organisms on Earth can be considered as a single system or global genome (Table 2.2, Fig. 2.5). It contains all the genetic information of all living organisms that exist on Earth, as well as numerous mechanisms for its implementation. This can be regarded as an information system, or genosphere, that covers the entire planet. The genomes of the numerous taxa consist of the sum of the genomes of all living bodies of the corresponding taxonomic units. The genomes of taxa determine the crucial differences between large groups of living bodies following diverse paths of development and evolution. The genome of a species should be separately distinguished among these, since it determines the species-specific and individual characteristics of a representative that possesses an individual life and is directly involved in the processes of genome reproduction through replication and transmission to a daughter organism. Multicellular organisms have an aggregate genome that includes all genomic information from all differentiated parts of the body. The genetic basis of a multicellular organism is the genome of its stem cells, which are the direct heirs of the zygote. Countless representatives of millions of species of creatures have individual genomes, which are the components of the genosphere of the planet.

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Fig. 2.5 The two integral components of the unified system of life. The totality of the genomes of all living beings on the planet makes up the single system we call the global genome or genosphere. It can be regarded as a nucleic acid network covering the entire planet (Genet). Everything in it is interconnected, and changes in any part of the network can cause impulsive fluctuations in many others. The totality of the phenomes of all living beings is the single system we call the global phenome or phenosphere. It is also a system that represents a single protein network that covers the entire Earth (Phenet). Mutually conditioning each other, the global genome and the global phenome constitute and support the planetary system of life

The phenome is the part of a cell that surrounds and integrates the genome into itself, forming a monolithic body (see Fig. 2.4). The phenome of a multicellular organism is composed of an organized mass of cells and intercellular substances. Phenomes are used by genomes to interact with other genomes and the environment. By analogy with the classification of genomes, a classification of the phenomes of our planet can be proposed (Table 2.3). Thus, the entire set of living bodies can be considered as a single global phenome. (Table 2.3, Fig. 2.5). This material system contains all living organisms that exist on Earth. By analogy with the genosphere, this can be regarded as the phenosphere, which covers the entire planet. The global phenome includes the phenomes of all taxa of living bodies. The phenome of a species should be separately distinguished among these, since it determines the species-specific and individual characteristics of an individual, and is also alive and directly involved in the processes of reproduction of individuals of its own species. Multicellular organisms have a complex phenome that includes all the traits of their species based on the implementation of genomic information from all differentiated parts of the body. The phenotypic basis of multicellular organisms is the phenome of trillions of differentiated cells. Countless representatives of millions of species of unicellular and multicellular creatures possess individual phenomes, which are the material components of the biosphere of our planet.

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Table 2.3 Conditional classification of different phenomes Type of phenome

Phenome characterization

Phenome of prokaryotes

The phenome of prokaryotes is represented by a cytoplasm, which integrates the nucleoid, and the surface apparatus, which segregates the cells. It is a microscopic living body with all inherent features and characteristics

Phenome of eukaryotes

The phenome of eukaryotes is represented by the cytoplasm, which integrates the genome-nucleus, and the surface apparatus, which segregates the cells

– Unicellular organisms

The phenome of unicellular organisms is represented by the cytoplasm, which integrates the genome-nucleus, and the surface apparatus, which segregates the cells. It is a microscopic living body with all inherent features and characteristics

– Multicellular organisms

The aggregate phenome of a multicellular organism is composed of an organized mass of cells and intercellular substances. It is a large living body with all inherent features and characteristics

Phenome of a biological species

The phenome of a species is a set of characteristics of individuals of a given species

Phenomes of taxa

The phenomes of taxa are a group of organisms that have fundamental similarities in structure, functioning, and pattern of life

Global phenome

The global phenome is a comprehensive biological system that consists of all living organisms on the planet

Planetary system of life. Discrete genomes are united by a single nature of nucleic acids and genetic information into the global genome system, forming a single information field of life (Fig. 2.5). This is the informational component of life. Expression of individual genomes causes specific manifestations in the form of living bodies. Then the totality of all organisms of living nature appears as the system we call the global phenome (Fig. 2.5). This is the material component of life. Discrete organisms are united by a single protein nature of living bodies into the global phenome system. Thus, “the totality of life on Earth” constitutes the extensive system of the global phenome, which is the product of the expression of the global genome. Existing and functioning interdependently, they form the planetary system of life, as a set of all interacting and interconnected genomes and phenomes (phenosphere + genosphere) that determine the phenomenon of life. They are united into a comprehensive system by the interdependent coexistence of matter and information in living bodies. These concepts once again point to the integrity of the phenomenon of life, despite the various discrete forms of its genotypic existence and phenotypic manifestation. The phenosphere and the biosphere. According to Vernadsky, the biosphere is a complex system consisting of “living matter”, viz., the totality of living bodies on

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Earth, and “bio-inert matter”, created jointly by living bodies and inorganic processes. That is, the biosphere is a conventionally identified part of the Earth’s nature. At the same time, the phenosphere, in our conceptualization, is a part of the phenomenon of life: it is that part of the biosphere which consists only of “living matter”. The phenosphere is composed of millions of individuals of different species of animals, plants, fungi, protozoa, bacteria, and viruses. The phenosphere is the interconnected unity of all living organisms. Phenomenon of life. Figure 2.6 is a schematic representation of the components of the grandiose phenomenon of life. The totality of genomes is a system of a multitude of nucleic acids containing all information about the entire set of living bodies. This is the genosphere or the informational part of the phenomenon of life. This system has the ability to replicate, which prolongs the existence of genomes. It is characterized by the ability to realize the virtual genetic information into the material structure of the phenome of a living body with an individual life. Individual life is represented by discrete living bodies of various biological species. Living bodies are the constituent elements of the planetary system of life. Individual life is primarily characterized by the ability of living bodies to self-recover

Fig. 2.6 Components of the phenomenon of life

2.7 Summary

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and produce their own kind. For the living bodies themselves, heredity and reproduction are useless, but they prolong the existence of the planetary system of life. Individuals are also incapable of variability and evolution. Individual lives have bodies, but do not possess immortality. Planetary life is the totality of all living bodies on Earth, from viruses to mammals. This is the phenosphere or the material part of the phenomenon of life. Despite the huge diversity of biological species, it is characterized by the unity of genetic information and the unity of protein structure and functions. The long-term integrity of the planetary system of life cannot be sustained without the reproduction of mortal organisms as its components. This system of planetary life is immortal, as it is capable of variability and evolution, based on the inevitable death and constant reproduction of its elements. Each of these biological systems has many peculiar inherent properties which will be further described in this book. And only their totality can relatively completely characterize the phenomena of life.

2.7 Summary The planetary system of life is an integral phenomenon, although it is represented by the huge variety of the totality of living bodies. The infinite and eternal nature of planetary life is due to the ability of mortal organisms to reproduce their own kind, which will in turn reproduce their own kind, and so on without the end. The system of life on Earth has numerous levels of organization, from atoms and molecules to ecological systems. Complex heterogeneous living systems are capable of self-organization. Order, as one of the main characteristics of life, arose from the chaos of the material world in the process of self-organization, based on the physical and chemical laws of the interaction of molecules and their systems. The whole colossal range of species of living bodies has a unified genetic code, a unified molecular composition, and uniform principles of organization, functioning, reproduction, and development. Thus, the visual ecomorphological diversity of living bodies is an illusion that hides the true simplicity and unity of life. The sum of the genomes of all living beings on the planet makes up a single system which we call the global genome. The sum of the phenomes of all living beings constitutes a single system which we call the global phenome. Mutually conditioning each other, the global genome and global phenome form the planetary system of life.

Part III

Living Bodies. Individual Life

Living bodies are physical bodies that have biological properties and characteristics. Only unicellular and multicellular organisms are living bodies that truly possess individual life. They are the organizers of the planetary system of life and the discrete units of the phenomenon of life. These autonomous, heterogeneous living systems are temporary and dissipative, but at the same time self-recovering and capable of reproduction. They are the possessors and bearers of individual life, a unique attribute that belongs only to individual living bodies. It is based on the constant flow of a set of physicochemical and biological processes aimed at self-repair and maintenance of homeostasis in each body. The process of individual life is connected with the temporary existence of organisms from their moment of appearance to death. A genome that has a fascinating ability to replicate is an inexhaustible source of reproduction of similar living bodies.

Chapter 3

Eukaryotic Cells

Cells are the basic living bodies. This is the primary level of possession of individual life. Cells are the units of structure and function of all living organisms. The detailed description of cellular life and properties is presented in Part 7 and in Sect. 1.13. In this chapter, the cell is characterized from the point of view of the peculiarities of organization of the living body as the holder of an individual life.

3.1 The Main Characteristics of Cells In the middle of the nineteenth century, Schwann, Schleiden, and Virchow formulated the main tenets of the cell theory on the basis of their microscope studies: • All living organisms are composed of cells. • The cell is the basic unit of structure and organization in all organisms. • Each cell arises from a pre-existing cell. Cell organelles were discovered in the late nineteenth and early twentieth centuries. By the middle of the twentieth century, the detailed structure of the cell—its ultrastructure—could be studied using electron microscopy. The achievements of modern cytology, biochemistry, biophysics, molecular biology, and genetics have significantly expanded our understanding of the cell and further developed the cell theory. Let us list the conventional characteristics of cells: 1. 2. 3.

The cells of all living organisms are homologous and have a wide range of similar characteristics. All cells are microscopic in size (0.1–100 µm), with rare exceptions. All cells are composite autonomous, discrete, heterogeneous systems, consisting of a variety of molecules, molecular complexes, organelles, and compartments. These numerous highly ordered subsystems are mutually integrated and interdependent, forming a single monolithic cellular body (see Fig. 3.1).

© Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_3

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Fig. 3.1 A cell is an open functioning system with several levels of complexity. The first level is a solid monolithic cell body. The second level contains three dominant macrostructures: (A) The genome (nucleus), as the systemic center of administration. (B) The phenome (cytoplasm), as the executive system of the genome. (C) The surface apparatus (cytoplasmic membrane, cell wall), as a system for isolating the cell and connecting it with the external environment. The third level is the system of intracellular membranes, as a single organ with a variety of properties and functions: isolation, protection, selective transport of substances and water, compartmentalization, formation of a large surface of phase separation, formation of an extensive hydrophobic zone, and so on. The fourth level is a system of intracellular compartments that perform different functions: cytosol, mitochondria, endoplasmic reticulum, lysosomes, etc. The fifth level includes macromolecular complexes: special membranes of organelles, ribosomes, polysomes, nucleosomes, chromatin, centrioles, microtubules, microfilaments, etc. The sixth level of complexity is polymers and macromolecules: proteins, nucleic acids, polysaccharides, and lipids. The seventh level is monomers, substrates, and simple organic molecules: glucose, ribose, amino acids, nitrogenous bases, carboxylic acids, glycerin, pyruvic acid, acetyl coenzyme A, etc. The eighth level is inorganic molecules: water, salts, and gases; The ninth level is ionic and atomic. The tenth level is the fundamental particle level of protons and electrons. 1—nucleus, 2—nucleolus, 3— cytoplasmic membrane, 4—lysosomes, 5—rough endoplasmic reticulum (RER), 6—mitochondria, 7—euchromatin, 8—heterochromatin, 9—Golgi apparatus, 10—cytoplasm, 11—ribosomes

4.

Each cell necessarily has three main macrocomponents, due to the unity of origin and the similarity of the basic principles of survival, reproduction, and development: (a) The genome—a set of genetic material; accumulator, generator, and operator of genetic information. This is the control center of individual life. (b) The phenome—cytoplasm, saturated with molecules, organelles, and enzymes that transform substances and energy. This is the executive system of the genome. (c) The surface apparatus (including the cytoplasmic membrane) isolates the living body and comes directly into contact with the external environment, providing communication and selective metabolism. The surface apparatus is also part of the phenome—the phenotypic framework of the genome.

3.1 The Main Characteristics of Cells

5.

6.

7.

8.

9.

10.

11.

12.

13. 14. 15. (a)

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All cells have essentially the same molecular composition (H2 O and a range of salts, proteins, nucleic acids, lipids, carbohydrates, and certain other molecules). Moreover, the concentration of various components is many times higher than in the external environment. At the same time, organic substances such as proteins and nucleic acids, are inherent only in cells. Cells are complex technical and engineering microconstructions. All molecules are located in a regular and orderly manner in the cell, forming various complexes, organelles, and compartments. Moreover, the molecules are selected and assembled on the basis of the laws of physics and chemistry; in all cells of one organism, organelles are built according to a single design; molecules are strictly adjusted to each other; special chemical bonds of molecules and physical interactions ensure the stability, strength, and reliability of this engineering complex; interactions of specially selected and specially located molecules and atoms provide for specific functions. The inner space of cells is divided by biomembranes into specialized structural and functional blocks called compartments. Many organelles are surrounded by membranes involved in their functional activity. An extensive network of membranes creates a huge system of phase separation inside the cells, where specialized processes take place. Multicellular organisms are complex systems of various cells of a single species of genome, united into a single multicomponent body. Many groups of cells are differentiated. They have a distinct structure and are specialized to perform certain functions; they can form tissues and organs. The initial cells of a multicellular organism are totipotent, that is, their genomes contain all the potential genetic information required for construction of the whole organism. The specialization and activity of cells of multicellular organisms is associated with the specifics of their structural organization and the specifics of the composition and orderliness of macromolecules, this being ensured by the differential expression of their genome. All cells reproduce, grow, and live on the basis of genetic information. They have essentially the same molecular genetic code, the same mechanism for recording and realizing genetic information (DNA → RNA → protein → trait), the same processes of transcription, translation, and expression, and the same enzymes for their maintenance. Genetic information is realized only in the form of proteins. All other characteristics and features of cells and organisms (for example, the synthesis of lipids and carbohydrates, the creation of macromolecular complexes, the creation of the internal architecture of cells, etc.) result from the work of protein enzymes. Cells have a varied, genetically determined, and limited lifespan. Cells multiply by division. Division is preceded by a doubling of the genome, which is based on the unique property of DNA replication. Any cell, in order to survive, has to: use enzymes to choose and constantly maintain unusually high rates of certain chemical reactions;

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(b) receive matter and energy from the surrounding space, transform them into the required forms, and purposefully use them to support integrity and functioning; (c) selectively absorb and discard substances; (d) store and use genetic information; (e) recognize signals from the internal and external environment and respond to them; (f) maintain integrity and homeostasis at all times. Thus, it is obvious that cells are extremely complex micro-bodies, and their ability to live is determined by the sum total of the listed attributes. Elimination or alteration of one or several of these characteristics leads to disruption or even termination of viability. That is why it is very difficult to name any one condition that makes the cell alive. Yet, it is definitely made alive by the entire set of the listed properties and attributes, and this whole set is necessary for life and survival under various conditions.

3.2 The Main Body Parts of Cells From the point of view of structural and functional organization, the three most important mutually integrated parts can be distinguished from the multitude of components of a eukaryotic cell (see Fig. 3.1): (a) the nucleus, as the backbone of information and genetic processes; (b) the cytoplasm, as the backbone of metabolism; (c) the cytoplasmic membrane, as the structural and functional envelope of a cell. Whereas, from the point of view of the central role of the genome, the same macrocomponents of cells can be described in the following way: (a) the genome, as the center of administration of the life of the cell; (b) the phenome, as the executive system of the genome; (c) the surface complex, as a system for isolating the genome and controlling its communication with the external environment.

3.2.1 Nucleus—The Site of the Genome The nucleus is the paramount compartment of a eukaryotic cell, where the genome is concentrated in an orderly manner as the genetic material and the tools for its manipulation (see Sect. 2.3 and Chap. 13). The nuclear envelope separates the genetic material and molecular genetic processes from the cytoplasm, and ensures the autonomy and independence of genetic mechanisms. Most cells contain only one nucleus. When the nucleus is removed from the cell, the cell cannot exist for very long, just as the nucleus itself dies when extracted from the cell. The nucleus is usually located in the center of the cell and has a spherical shape. The size of the nucleus of mammalian cells is on average 2–6 µm, which depends on the type of cell and its stage of activity. The nucleus usually occupies about 10–50% of the cell volume. The nucleus consists

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of several components that perform different functions: envelope, karyoplasm, chromatin, nucleolus, as well as other organized compartments called “membraneless organelles”. The dry matter of the nuclei contains about 80% proteins, 12% DNA, 5% RNA, 3% lipids, and a certain amount of Mg++ and Mn++ . The majority of proteins are enzymes, which can be thought of as “tools” serving the molecular genetic processes. In addition, histone and non-histone proteins, together with DNA, form a chromatin network. A certain part of the proteins forms the skeleton of the nucleus in the form of microfilaments and the nuclear lamina. This is a network of protein filaments lining the inner surface of the nucleus. Special proteins bind to rRNA and form ribosomal subunits. Some proteins and protein fibers are part of the nuclear pores. All of the above are also elements making up the extremely complex organization of the genome. The amount of DNA in an animal cell nucleus can vary significantly from species to species. The number of DNA molecules in the G1 and G0 phases of the interphase corresponds to the number of chromosomes (see Chap. 9). For example, there are 46 DNA molecules in the nuclei of human somatic cells, and 8 in the cells of a Drosophila fly. After the S phase of the interphase, the number of DNA molecules doubles due to replication (to 92 in humans and 16 in Drosophila flies). The lengths of DNA molecules are different for different species of animals (in humans, 1.0–2.5 cm). Each DNA molecule has its own sequence of nucleotides. In combination with proteins, DNA molecules form chromatin. Chromosomes are formed from chromatin during mitosis. Different genes of DNA serve as a matrix for the constant formation of mRNA, tRNA, rRNA, and other RNA subtypes. rRNA remains in the nucleus for some time to form ribosomes, while mRNA and tRNA (after post-transcriptional modification) immediately enter the cytoplasm through the pores of the nuclear envelope. The content of the nucleus (karyoplasm) is a densely structured colloid, mainly composed of proteins and nucleic acids. The karyoplasm is covered with a double membrane envelope with pores. The outer membrane has a structural connection with the membranes of the endoplasmic reticulum (see Fig. 3.2). Chromatin (heterochromatin and euchromatin), microfilaments, nucleolus, and enzymes are concentrated in the karyoplasm. On the inside, the nuclear envelope is covered with a protein network—a nuclear lamina that maintains the shape and volume of the nucleus. Chromatin filaments are attached to the nuclear lamina by telomeric regions. Microfilaments are long protein strands that cross the contents of the nucleus and form the inner “skeleton”. They stabilize the shape of the nucleus, and also serve as a place of attachment for chromatin. The inner “skeleton” of the nucleus is of great importance for ensuring the orderly flow of the main processes of replication, transcription, and post-transcriptional modification. The content of the nucleus is highly dynamic, depending on the activity of the cell. Outside, the nucleus is covered with microfilaments, which are elements of the cellular cytoskeleton. The genome of eukaryotes is located primarily in the cell nucleus. We consider it not only as the set of genetic information needed to create and maintain the life of an individual, but also as a specialized semi-autonomous structural–functional

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Fig. 3.2 Diagram of the structural organization of a nucleus. This intricate structure is the site of localization of the genome—a complex system for storing and manipulating genetic information. It is the control center for the life of a cell, organ, or organism. 1. Outer membrane of the nuclear envelope. 2. Inner membrane of the nuclear envelope. 3. Intermembrane space. 4. Nuclear pore. 5. Nuclear lamina. 6. Euchromatin. 7. Heterochromatin. 8. Ribosome. 9. Nucleolus. 10. Rough endoplasmic reticulum

complex. That is, everything described above as attributes of a nucleus are in fact the paramount components of the genome system. Karyoplasm is a specific environment for the molecular genetic processes of the genome. The complex of enzymes involved in replication, transcription, splicing, post-transcriptional modification, and so on, are the tools with which the main genomic processes are carried out. The nuclear envelope separates the molecular genetic processes from the cytoplasmic metabolic processes. The nuclear lamina and microfilaments fix and orient the genetic material for the implementation of genomic processes. The randomly scattered chromatin is actually located in a strict and orderly manner in the nucleus, thus allowing for the differential expression of its specific regions. On the basis of its ability to replicate, the genome is capable of reproduction, and on the basis of transcription, the genome directs the synthesis of the entire mass of proteins and other molecules which it uses to build a phenotypic framework around itself. The genome, as an autonomous entity, contains not only the information, but also the entire set of tools and mechanisms for manipulating it. Thus, we can say that the nucleus is the location of the key player within any cell, namely the body of the genome. The main functions of the nucleus and genome are: 1. Storage of genetic information, which is recorded in DNA molecules based on the genetic code. 2. Realization of genetic information based on transcription, which determines the synthesis of proteins. This maintains and ensures the orderliness, metabolism, functions, and division processes of the cells.

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3. Transmission of hereditary information to subsequent generations on the basis of DNA replication, involving the formation of chromosomes and their division. The most important molecular genetic processes in the nucleus are replication, transcription, post-transcriptional modification, and formation of ribosomes (see Chaps. 13 and 14).

3.2.2 Cytoplasm—The Site of the Phenome The cytoplasm in eukaryotes usually constitutes the bulk of the cell. This includes all its internal contents, with the exception of the nucleus. It contains roughly 75– 85% water, 10–20% proteins, and a range of other substances in relatively small amounts. Under a light microscope, the cytoplasm appears to be a homogeneous, colorless, transparent, viscous liquid. However, electron microscopy revealed the complex multicomponent, multifunctional, highly ordered structure of the cytoplasm. The cytoplasm consists of cytosol (the cytoplasmic matrix), the cytoskeleton, cell organelles, and inclusions. Cytosol. Cytosol is the fluid part of the cytoplasm (about 55% of the total cell volume) outside of the organelles. It is a structured colloid consisting of a complex mixture of organic macromolecules dissolved in water: proteins, fats, carbohydrates, small organic molecules (amino acids, glucose, nucleotides, fatty acids, etc.), as well as inorganic substances. Cytosol contains thousands of different types of proteins, mainly enzymes. Chemical composition and properties of cytosol. Cytosol contains both inorganic substances (water, salts, gases) and organic substances. Water is the main constituent of cytosol; it provides for almost all vital processes in cells (see Sect. 1.7). In particular, a liquid aqueous medium has the following properties: • water is a solvent for almost all substances in the cell, providing the dissociation of many substances and thereby facilitating chemical reactions; • it promotes the movement of substances in a dissolved state within the cell and from one cell to another; • it is a good thermal stabilizer, retaining the heat generated by the cell; • it provides for constant Brownian motion of molecules, which is the physical basis of metabolism. Salts make up 1–2% of the mass of cytosol. They form ions in the aquatic environment. Most of the cell salts are carbonates, bicarbonates, phosphates, sulfates, and chlorides of sodium, potassium, calcium, magnesium, and iron. They play an essential role in maintaining the osmotic balance and acidity of the cytosol. Many participate in biological processes and are a part of certain proteins. Gases. Oxygen, carbon dioxide, nitrogen, and ammonia are found in animal cells. Oxygen and nitrogen come from the atmosphere by diffusion. Carbon dioxide and

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ammonia are produced in cells during metabolism. CO2 is formed during oxidative reactions and is constantly being evacuated from cells. Nitrogen is an inert gas, so does not participate in cellular reactions. Ammonia is rapidly metabolized and excreted from the body. Organic matter constitutes up to about 20–25% of the cytosol. The main groups of these substances are proteins, along with fats, carbohydrates, and nucleic acids (see Chap. 1). Their main role is to provide the specificity of the structure and function of cells. Cytosol also contains a wide range of amino acids, fatty acids, and various other small molecules of organic substances, which serve as energy substrates for oxidation, provide a means of storage, and so on. Physicochemical properties of cytosol. The content of the cell is an organized, dispersed colloidal system. The colloidal content of cytosol can pass from a less structured state, a sol, to a more structured one, a gel. Changes in the colloidal state are associated with a different distribution of colloidal particles in the cytosol. In the sol state, cytosol particles, mainly proteins, are distributed more or less randomly and evenly, which ensures good molecular mobility. In the gel state, the particles form aggregates with each other and with water. This forms a volumetric network that structures the cytosol and leads to a loss of fluidity in the cytoplasm. Here, the mobility of molecules decreases significantly. This means that in regions of “solid” cytosol, the rate of metabolic reactions is limited, but in regions of “liquid” cytosol, rates of biochemical processes approach their maximum. The transition of sections of the cytoplasm from the gel to the sol state, and vice versa, is ensured by cyclosis—motion of the cytoplasm. This process, for example, underlies the formation of pseudopodia in amoeba and leukocytes. There is constant Brownian motion of molecules in cytosol, ensuring frequent collisions and hence a high rate of metabolic reactions. The colloidal state of cytosol maintains the volume and shape of the cell, while a constant pH is maintained with chemical buffers. Brownian motion of molecules depends on the state of the cytosol: the more “liquid” it is, the more intense the molecular motion. A rise in temperature will also lead to an increase in the intensity of the motions and accelerate any biochemical reactions. Brownian motion is due to the thermal motion of molecules. Here, each molecule rotates and shuttles, thus ensuring frequent collisions. For instance, each cytosol molecule experiences about one million collisions per second. Thus, the Brownian motion of cytosol molecules is a necessary condition for the occurrence of all metabolic reactions. Biological properties of cytosol. The chemical and physical properties of cytosol determine the biological properties which ensure the structural integrity and functional activity of cells. The first of these is the maintenance of metabolism. Cytosol is a medium in which thousands of biochemical reactions can take place simultaneously. It is estimated that about 70% of cellular metabolic reactions occur in the cytosol, which contains thousands of different types of enzyme. Among them are reactions such as glycolysis, gluconeogenesis, and synthesis of proteins, fatty acids, amino acids, nucleotides, and others. Many proteins are synthesized on ribosomes in the cytosol. These proteins are usually used by the cell for its own purposes. Ribosomes associated with endoplasmic reticulum usually generate proteins “for

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export”. The constant cytosol environment provides the necessary conditions for the proper functioning of all cell organelles. Organelles obtain the required substances from the cytosol and discard their waste products into it. Cytosol is involved in the maintenance of homeostasis in the cell organelles. The reactions taking place in the cytosol ensure the stability of the composition and structural organization of cells and tissues. The concentrations of water, gases, substrates of chemical reactions, and pH are kept constant in the cytosol. These conditions ensure the flow of biochemical and physiological processes. As a result of the continuous synthesis of molecules (proteins, amino acids, nucleotides, carbohydrates, fats, etc.), old, worn-out, damaged molecules can be exchanged for newly synthesized ones. This also applies to the constant maintenance of the structure and composition of all organelles. Cytosol contains non-lysosomal proteases that digest short-lived and defective proteins. It is also a reservoir for thousands of different substrates (amino acids, nucleotides, glucose and others) that are continuously used in metabolism to form new structures or transform energy. Cytosol includes the cell’s cytoskeleton, which is a flexible, mobile protein network in the inner space of cells, consisting of microtubules, microfilaments, and intermediate filaments. It is inherent in all eukaryotic cells. The cytoskeleton maintains the shape of the cell, ensures its mobility and the motion of cell organelles, binds and fixes specific enzymes in certain places within the cytosol, and ensures cell attachment to other cells and the substrate. Fibrils of the cytoskeleton have the ability to assemble from protein monomers, when necessary, and disassemble after performing their function. They are capable of contraction and motion. Fibrils interact with each other through auxiliary proteins. Cytosol ensures the growth and differentiation of cells. After division, the cells are smaller in size and still poorly differentiated. Cell growth is primarily associated with the synthesis and accumulation of all the necessary organic substances, most of which are formed in the cytosol. These substances increase the volume of the cell, and are also used in the formation and growth of all organelles. Specific organelles appear in the process of cell development; the shapes of the cells change and they gradually acquire the features and properties of their ancestors. Thus, cytosol is one of the key components of the cell. Intracellular circulation of substrates and metabolites. According to modern concepts, the cell is not a simple disordered “sack” of enzymes, where processes occur only through diffusion. The cell is a highly ordered system of macromolecules, and at the same time, a system for the circulation of aqueous solutions of small molecules. Ultrastructural and cytochemical studies indicate that the cell is a threedimensional microcosm built of macromolecules and membranes, which houses a complex of organelles and vesicles and is filled with filaments, trabeculae, “pumps,” and “channels”. Cytosol is not a static solution where only diffusion is observed, but a “living”, mobile compartment of the cell. In it, one observes the movement of organelles, vesicles, various particles, and regions of the cytoplasm. In larger cells, “flows” of substances have been recorded at speeds of 1 to 80 µm/sec. These processes are controlled by the cell and change depending on the metabolic state. They are based on ATP-dependent “myosin engines” that activate actin filaments

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for the intracellular circulation system. Besides, many metabolic pathways and their enzymes are located in specific compartments, and many “soluble” cytosolic enzymes are fixed in groups at certain sites within the cytosol. Thus, orderliness, structure, and controlled circulation play a central role in cellular metabolism. The intracellular mobility of enzymes and carrier proteins (for example, myoglobin) is significantly lower than in simple aqueous solutions. For example, the diffusion rate of myoglobin in cytosol is about 1/10 of the value in simple solutions. Thus, soluble enzymes and other proteins are rather limited in intracellular mobility. Ordering and structure determine the intracellular behavior of macromolecules and limit the mobility of enzymes, but do not limit the intensity of interaction between the enzymes and substrates. This can only be explained by the functioning of the controlled intracellular circulation system, which specifically delivers substrates to enzymes and removes metabolites. Due to the complexity of the internal organization of the cell, the mobility of small molecules should also be significantly limited in comparison with simple solutions. There are three factors that limit the mobility of cell molecules: (a) structuredness of the cytosol, (b) binding with other molecules, (c) collision with other particles. However, it has been found that the speed of motion of molecules inside the cell is reduced by only 25% compared to water. This once again indicates that there are special mechanisms that facilitate the motion of substrates to correlate with metabolic rate. It has also been found that organelles are moved around with the help of specialized transport systems using microtubules, which serve as intracellular pathways, and special motor proteins, dyneins and kinesins, which act as carriers. Thus, the orderliness and structuredness of the cytoplasm determine the intracellular behavior of metabolite molecules, restraining them from random diffusion, and moving them in an orderly manner and at high speeds if necessary. Most likely, this is due to the presence of an intracellular circulation system. This system provides fast motion and controlled connection of substrates and enzymes, depending on metabolic needs. By regulating intracellular flows, their rates can be rapidly increased by two orders of magnitude, which correlates with the possibility of increasing metabolic activity. Cellular organelles are differentiated sections of the cytoplasm of eukaryotic cells with a specific structure and molecular composition. These are complex, highly ordered biological systems of macromolecules that form a specific spatial structure capable of performing specialized cellular functions (Table 3.1). Eukaryotic cells contain many intracellular membranes, so almost half of the entire volume of a cell is enclosed in separate intracellular compartments, which we call “organelles”. The rest of the intracellular space is occupied by cytosol, which is the essential cell compartment. Cellular organelles are conventionally divided into membranous organelles, which are surrounded by a typical biomembrane, and non-membranous organelles, which do not have such a membrane. Membranous organelles can have a single or double membrane. The organelles listed in the table are found in the majority of eukaryotic cells.

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Table 3.1 The main cell organelles of eukaryotes and their functions Cellular structure

Description

Key functions

Nucleus

Large spherical structure, surrounded by a double membrane. Contains the nucleoplasm, chromatin, and nucleolus

The site where the genome is localized. Stores genetic information in the form of DNA; transmits hereditary information to descendants; controls metabolic activity

Cytoplasm

Consists of a basic substance (cytosol) with organelles

Provides for the flow of most metabolic processes; surrounds and integrates the genome to form an integral cell body

Cellular membrane

The outer amphipolar membrane Isolates and protects the cell of the cell, consisting of lipids and from the external environment; proteins regulates the permeability of a wide range of substances in and out of the cell; communicates with other cells; recognizes chemical signals

Rough endoplasmic reticulum

Complex of membrane tubules in the cytoplasm, covered with ribosomes

Synthesizes, modifies, stores, and transports proteins

Smooth endoplasmic reticulum

System of membrane tubules and vesicles in the cytoplasm of cells

Synthesizes, stores, and transports lipids and carbohydrates; detoxifies

Golgi apparatus

System of flat membrane discs in the cytoplasm of cells

Accumulates and modifies proteins, lipids, and carbohydrates; stores and transports macromolecules; forms lysosomes

Lysosomes

Spherical structures covered with a membrane and containing hydrolytic enzymes

Intracellular digestion of the main classes of organic substances; phagocytosis and neutralization of harmful particles; recyclization of basic macromolecules

Mitochondria

Oblong oval structures covered with a double membrane. The inner membrane forms cristae

Break down organic molecules to CO2 and H2 O; extract energy and store energy in the form of ATP

Plastids

Oval structures of plant cells surrounded by two (in some cases 3–5) membranes

Implement the process of photosynthesis; accumulatetarch, carotenoids, proteins, and fats

Peroxisomes and glyoxysomes

Membrane sacs containing oxidative enzymes

Break down hydrogen peroxide (continued)

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Table 3.1 (continued) Cellular structure

Description

Vesicles

Membrane vesicles, filled with the Provide for the transfer of products of the endoplasmic enzymes, polysaccharides, reticulum and Golgi apparatus glycoproteins, and so on, between the components of the cell and excrete the same into the external environment

Key functions

Ribosomes

Macromolecular complexes consisting of two subunits containing rRNA and proteins

Provide for protein synthesis

Cell inclusions

Substances temporarily located in the cytoplasm, vacuoles, or plastids

Represented by nutrients, pigments, and salt crystals

Cytoskeleton

Flexible, mobile network of protein filaments, consisting of microtubules, microfilaments, and intermediate filaments

Maintains the shape and volume of cells, and ensures the motion of cells and cell organelles; binds specific enzymes; attaches to other cells and surfaces

Centrioles

Paired structures formed by short microtubules

Forms the spindle apparatus and cytoskeleton filaments

Membraneless organelles. Eukaryotic cells, along with “classical” organelles with a membrane (mitochondria, lysosomes, endoplasmic reticulum, etc.), as well as stable non-membrane organelles (ribosomes, cytoskeleton, centrosome, etc.) are able to form temporary biomacromolecular condensates in the cytoplasm and in the karyoplasm, which play an important role in the cell compartmentalization system. Biomacromolecular condensates are phase-separated liquid “coacervates” formed according to the laws of physical chemistry of polymers as a result of phase transitions. They are specially organized sections of the cytoplasm, comparable in size to classical organelles. Fluctuating within the cell volume, such membraneless organelles contain not only proteins, but also specific RNAs. Depending on its needs, the cell can compartmentalize any part of the cytosol and bring it into a functionally necessary active state, something which happens all the time. The phenomena associated with this dynamic phase heterogeneity in the cell expand the possibilities for, and increase the efficiency of, many specific cell functions. Membraneless organelles are also formed in the nucleus, in places of specific activity of the genetic material. There are therefore no “voids” in cells; each minimal fragment matters. Special organelles are characteristic only of a certain type of cells that perform a special function. For example, in some protozoa it is a flagellum, a contractile vacuole, an undulating membrane, an axostyle, or mineralized integuments. In muscle cells it is a myofibril, in spermatozoa an acrosome, and so on. The cytoplasm and the surface apparatus constitute the phenotypic framework of the genome, or, simply put, the phenome. This is the structural complex of the cell, consisting of various elements of the cytoplasm and surface apparatus, which is a

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complex system of maintenance and defence. This is the part of the cell that surrounds and encompasses the genome itself, forming a single body. The genome controls the construction of the surrounding phenome, accomplishing four strategic tasks. Firstly, it creates a stable zone of comfortable existence where all the necessary processes for the supply of substances and energy of are provided. Secondly, it protects itself with the surface apparatus from direct contact with the external environment. Thirdly, it provides indirect contact with the external environment for the implementation of metabolism. Fourthly, it perceives information from the environment through a system of receptors. The cytoplasm is thus the largest highly important part of the cell, providing both structurally and functionally for all aspects of metabolism and numerous functions which ensure its own existence and that of the genome. Together with the surface apparatus, the cytoplasm integrates the genome within itself, forming a monolithic, autonomous cell body.

3.2.3 Surface Apparatus and Biological Membranes The surface apparatus is an extremely important component of any cell and an integral part of the phenotypic framework of the genome. It performs a number of key functions: (a) it serves as a barrier separating the uniquely organized contents of the cell from the external environment, thereby making the cell an autonomous body; (b) it provides the means for the interaction of the cell with environmental factors; (c) it can respond quickly and adequately to any changes in environmental factors; (d) it is an important tool for the interactions between cells and communication between them; (e) it is a means of combining cells into a multicellular organism; (f) it possesses selective permeability; (g) it regulates the supply of important substances and the removal of unnecessary ones; (h) it supports metabolism. The surface apparatus consists mainly of three complex components: (1) the cell wall (glycocalyx in animals and certain bacteria species), (2) the cytoplasmic membrane (plasmalemma), and (3) the cortical layer of the cytoplasm, located under the cytoplasmic membrane. The cell wall is the external skeleton of bacteria, protozoa, and fungal and plant cells. The plasmalemma is only around 10 nm thick, but it successfully fulfills a boundary role in relation to cell environment and performs selective, transport, and receptor functions. The cytoplasmic membrane of animal cells consists mainly of phospholipids and lipoproteins with embedded protein molecules that perform the functions of surface antigens and receptors. The integrity of membranes is maintained due to the self-organization of amphipolar phospholipids and proteins in the aqueous medium, without the expenditure of additional energy by the cell. The glycocalyx of animal cells consists of various of oligosaccharide, polysaccharide, glycoprotein, and glycolipid molecules fixed in the plasmalemma. It performs receptor and marker functions, and also connects cells to each other in tissues and organs. The cortical layer of the cytoplasm contains specific elements of the cytoskeleton, cascades of enzymes, and structural elements

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of channels, carriers, receptors, and so on. The shape of the cell also depends on the cytoskeleton organization in the cortical layer. The surface apparatus varies significantly in structure and function in different cells and organisms. Depending on the type of cells and living bodies, it can consist of combinations of many components: biomembranes with various kinds of organization, all kinds of cell walls, glycocalyx variants, villi and flagella, cytoskeleton elements, intercellular contacts, receptors, enzymes, and so on. Biomembranes are the backbone for the organization, structure, and function of the surface apparatus. All cells, without exception, as well as some viruses, are surrounded by a membrane. The cytoplasmic membrane (plasmalemma) covers the cell from the outside and is paramount in the system of biomembranes, a necessary condition for the existence of any cell. The cytoplasmic membrane obeys the same structural principle as other biomembranes. However, its structure is more complex, since it is a multifunctional system that performs a greater number of general functions important for the cell as a whole. In addition to lipids and proteins, the cytoplasmic membrane also includes glycolipid and glycoprotein molecules with branched carbohydrate chains. These chains intertwine with each other on the cell surface, forming a peculiar framework with intertwined protein molecules (glycocalyx), consisting of oligosaccharides covalently linked to glycoproteins and glycolipids of the plasmalemma. The functions of the glycocalyx are: (a) intercellular recognition, (b) intercellular interaction, (c) joining and binding of cells into tissues, and (d) parietal digestion. In addition, biomembranes play a key role in the organization of the intracellular membrane system. Most cellular organelles are based on membrane structures. They are inherent in the endoplasmic reticulum, the lamellar Golgi complex, membranes and cristae of mitochondria, lysosomes, vacuoles, plastids, the nuclear envelope, and the outer cell membrane. Membranes are highly ordered complex molecular systems responsible for the structural organization and vital processes of cells. For example, they ensure the division of the contents of the cell into specialized closed compartments, which allows various, even multidirectional, processes to proceed simultaneously in the cell. In prokaryotes, division into functional areas is possible due to protrusion of the plasmalemma into the cell cavity, but also by the creation of membrane-like partitions (proteins and single-layer lipids). Membranes regulate the metabolic pathways of the cell, maintain the required concentration of substances (ions and metabolites) through their selective movement, create electrical potential differences, produce phase separation, participate in enzymatic processes, and so on. Membranes are the backbone for the precise allocation of enzymes, thereby determining a strict sequence of biochemical reactions. For example, proteins are synthesized and modified in the rough endoplasmic reticulum, and fatty acids in the smooth endoplasmic reticulum; the oxidation of organic substances is carried out in the mitochondrial matrix, and the synthesis of ATP on the inner membranes. Membranes are an important part of the surface apparatus, providing selective transport and communication of cells and genomes with the external environment. Thus, the surface apparatus and biological membranes perform a number of vital functions, ensuring the adaptation and survival of cells and their genomes.

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3.3 Cellular Nanoconstruction All molecules are located in a regular and orderly manner in the cell, forming various complexes, organelles, and compartments. This ensures the regularity and orderliness of metabolic reactions and cell functions. Depending on the composition and degree of ordering, complexes of organic molecules are capable of performing certain functions. For example, the molecules necessary for the cell are transferred selectively from the external space by special carrier proteins. These proteins capture only the required substances, and do not let through the harmful or unnecessary ones. Thousands of diverse biochemical processes in cells are ensured by thousands of different catalyst protein molecules (enzymes). The function of cellular respiration and oxidative phosphorylation (energy conversion) is carried out by protein enzymes of the respiratory chain and an enzymatic molecular complex ATP synthase. Muscle cells are contracted by the interaction of actin and myosin molecules with the energy supplied by ATP molecules. Thus, cells are autonomous highly ordered molecular systems capable of self-organization, self-regulation, and self-preservation. Despite their internal heterogeneity, they are integral units, even when they are a component of multicellular organisms. Each individual cell or organelle, or structural and functional part of a cell, can be viewed as a complex engineering and technical construction, precisely assembled from a variety of molecular elements. This is evidenced by the following facts: (a) organelles are built from certain building-block molecules; (b) molecules are selected and assembled according to the laws of physics and chemistry; (c) organelles in all the cells of a given organism are built according to a single design; (d) molecules in macromolecular complexes are strictly adjusted to each other, literally with mathematical precision; (e) special chemical bonds of molecules and physical interactions ensure the stability, durability, and reliability of the engineering complex; (f) the interactions of particularly selected and specifically located molecules and atoms provide for specific functions of this complex; (g) typical physicochemical processes and functions of organelles in various cells (and even organisms) are ensured by a standard set, arrangement, and interaction of molecules and atoms; (h) the functioning of such technical systems is cooperative, consistent, and interdependent; (i) unnecessary molecules and their complexes are absent from the nanoconstructions of cells; (j) no by-products are formed in the process of operation of cell conveyors for the transformation of substances and energy, or they are immediately utilized; (l) the performance of a certain work by the cell requires a minimum energy use.

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Examples of nanodevices and nanoprocesses are: the structure and functioning of nucleic acids, the structure and functioning of ribosomes, the design of flagella, the organization of biological membranes (see Fig. 6.1), the highly complex enzyme ATP synthase (see Fig. 7.3), and many more. Structurally controlled processes. Most of the physicochemical processes in cells are structurally determined and structurally controlled. This includes, for example, membrane transport processes and all enzymatic transformations. Even the chaotic thermal motions in cells are controlled by the formation of membranes, as the structures that divide space. The main purpose of the structure is to control and manage the flows of matter, energy, and information, as well as to enable functions, while the main purpose of those functions is to maintain structure and perform useful work. The complex engineering structures of interacting macromolecules, organelles, and cell parts form complex “technical systems”, such as a protein synthesis system, a vesicular transport system, a membrane energy transformation system, etc., which exist and function as a single device. Moreover, they are interconnect and interact with all other macrostructural and microstructural constructions of cells. It is their well-coordinated interaction that ensures the life and functioning of cells as integral autonomous bodies. Hence, it can be argued that the regular and ordered arrangement of molecules in cells ensures the regularity and orderliness of metabolic reactions and cellular functions. That is, interrelated structurally determined and structurally controlled physicochemical and biological processes occur within the cells. Therefore, any violations of the structure lead inevitably to changes in the functions. It is also essential that all organelles are “submerged” and interact with the complex structure of the cytosol. As they exist in a single operative space, mitochondria, lysosomes, membranes and vesicles of the endoplasmic reticulum and Golgi apparatus, ribosomes, chromosomes, and so on are in constant motion within it, synchronously and interconnectedly changing their shape and size, as well as their structural and functional state. Thus, cells are precisely constructed engineering nanoconstructions, the cementing and driving forces of which are electrostatic, electrodynamic, and quantum mechanisms (see Chap. 7). This is an intricate, highly ordered unity of organic and inorganic molecules, their ionized forms, and their highly organized heterogeneous complexes. Depending on the molecular composition and degree of orderliness, these nanoconstructions are capable of performing specific functions. The totality of molecular engineering complexes generates various organelles and cell structures that form highly organized cellular nanosystems. In turn, these systems are either single-celled individually living organisms, or units of the structure and functioning of multicellular bodies.

3.4 Cells and Their Fragments in Vitro The cultivation of tissues, cells, and organelles is a common method for studying various aspects of their activity. Isolated cells and organelles can generally retain

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functionality, autonomy, and integrity in artificial isotonic nutrient media for anything from a few hours to several weeks. For a certain time, cells can maintain their shape, composition, metabolism, and homeostasis, and as well as performing their functions. Many types of cells retain the ability to divide, grow, and differentiate in vitro. For example, mesenchymal cells from the bone marrow can live in culture for up to 2.5 months and amnion epithelial cells for up to 3 months, while cells from a blastocyst can grow for years and some cancer cells and “immortalized” cell lines last for decades or more. These data indicate autonomy as one of the main characteristics of cells, along with their significant durability margin. Using modern methods of fractionation, a cell can be decomposed and divided into its constituent parts: nucleus, mitochondria, lysosomes, ribosomes, and other organelles. Isolated membranes, chromosomes, cytoskeleton proteins, enzymes, DNA and RNA macromolecules, carbohydrate polymers and monomers, and various types of lipids can be obtained. Various cell processes, such as protein synthesis, can be implemented “in a test tube”, under appropriately created artificial conditions. For this purpose, cells are homogenized (minced) and centrifuged to obtain ribosomes. The structureless supernatant contains only ribosomes, RNA, ATP, and small molecules and their complexes. If radioactively labeled amino acids are added to this supernatant, the generation of new proteins can be observed using the methods of electrophoresis and autoradiography. Cell-free systems may be generated after homogenization and fractionation of cells of various tissues. The resulting fractions (nuclei, mitochondria, lysosomes, ribosomes, etc.) can then be placed in physiological solutions where isolated molecular systems of cells are capable of performing their biological functions. That is, many processes can proceed independently and in an organized manner even in the absence of the organization provided by the integral autonomous cell. Enzymes and macromolecular complexes are the centers of organization of such processes. For example, the presence of ribosomes in a test tube is a prerequisite for the biosynthesis of highly organized polypeptides outside of the cell. Naturally, the presence of amino acids, GTP, and a number of other biosynthesis factors is also required for this process to occur. When everything is available, the process occurs spontaneously, automatically, and in an orderly and organized manner. It will continue as long as there are enough substrates and factors in the test tube for the self-organizing process to take place. The simplest self-organizing system of biomolecules is the presence of interacting enzymes and their substrates in a cell-free environment. A sufficient concentration enables self-organization of the process of transformation of particular organic substances (substrates) into other specific substances (products). Apparently, such self-organizing transformations are very important for the existence of cells. It is also possible to obtain isolated mitochondria by homogenization and centrifugation, place them in a test tube, add ADP and substrates, and then record the O2 uptake and ATP formation under artificial conditions. Biotechnologists and molecular biologists successfully manipulate DNA molecules, transfer genes, and create transgenic organisms, and scientists have learned to transplant nuclei, mitochondria, and cytoplasmic regions.

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It is possible to isolate virtually any organelle and study its structure and functions outside the cell for several hours or days. The activity of almost any enzyme can be studied in a homogenate of cells or even in isolation. Moreover, almost all simulated processes can be regulated in vitro by adding substrates and inhibitors, or changing the temperature, osmotic pressure, pH, and so on. However, a whole cell cannot be reassembled from its separate parts. It is impossible to restore its integral metabolism and various cellular functions, such as nutrition, motility, contraction, multiplication, and so on. Moreover, it has not yet been possible to create even a primitive cell artificially. However, isolated nuclei can be transplanted into denucleated cells. That is, a temporarily separated genome and phenome can be reunited into a fully-fledged cell. This demonstrates the limits of the reversible division of a cell into just two parts, which is consistent with our concept of the monolithic coexistence of the genome and its phenotypic framework in a single living body (see Fig. 2.4). The following conclusions can be drawn from the facts presented above: (a) the relative autonomy of cellular organelles and the automatism and spontaneity of individual cellular processes are revealed; (b) the implementation of such processes is possible in an unorganized environment (outside the structurally organized colloidal cytosol or matrix); (c) self-assembly of some cellular structures and self-organization of some processes is possible; (d) the basis of all biological processes is the presence of spontaneous undirected random processes: chaotic thermal motion, diffusion, osmosis, adsorption, and other physicochemical properties of colloidal solutions; (e) the key task of maintaining order in a cell is reduced only to the regulation of direction and rates of biochemical and biophysical processes, which serves as the basis for the emergence of functions; (f) consequently, individual self-oscillating “biological” processes could have arisen at the dawn of evolution, even earlier than the cells themselves, and proceeded cyclically in some specific closed microspace. Thus, many intracellular processes can be carried out outside of a highly organized cell, under artificial chaotic conditions which only mimic those in the cell! This paradoxical fact seems to contradict the idea that a high level of structural organization is needed in cells for metabolic processes. Clearly, the key here is to have a maximally compressed, organized packing of all structures and processes into the single operative microspace that constitutes a cell; this then forms the “critical mass” that leads to the explosion of emergence and the appearance of the “perpetual motion machine” of the individual lives of cells. In this case, the structure becomes a function, and the function becomes a structure, forming a qualitatively new conglomerate possessing life.

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3.5 Why is the Cell Needed? We already emphasized earlier that the phenomenon of life has a dual nature. On the one hand, life is associated with the process of existence of separate living bodies (cells and organisms), while on the other hand, it is a planetary system (see Chap. 2). Cells are the basic structure of the phenomenon of life. Neither the genome, nor its phenome separately possess an individual life. The latter, together with the unique abilities of living bodies, appear only at the level of monolithic organisms. In particular, under the control of the genome, cells are capable of: (a) (b) (c) (d) (e)

selectively extracting substances and energy from the surrounding environment; transforming these substances for the own purposes; implementing self-repair; performing useful work; dying and reviving again in the form of a new generation.

On this basis, cells have extraordinary powers and are needed to implement the far-reaching plans of Nature: 1. Cells contain life in the form of genomes in a phenotypic (bodily) framework. That is, cells are monolithic bodies, consisting of a genome and a set of genomeorganized structures and processes (phenome) which continuously transform matter and energy for their own survival and reproduction. 2. Cells transmit life, i.e., they transmit their genomes to descendants. A cell does this by doubling its DNA, generating homologous genomes, and then splitting them into daughter cells. In essence, the genome uses its phenotypic environment for its own existence, reproduction, and subsequent translocation into another, renewed body. 3. Cells form multicellular bodies that consist of a mass of various types of cells with different shapes and contents, creating diverse tissues, organs, and body parts that perform numerous functions that contribute to adaptation and survival. A multicellular organism is formed as a result of the differential expression of a single genome. 4. Cells and multicellular bodies determine the planetary system of life and the very phenomenon of life. This is a continuous process of the existence and functioning of a single system of all unicellular and multicellular organisms. This is an integral phenomenon, a single immortal living organism, although it is represented by an infinite number of discrete carriers of individual life.

3.6 Summary Cells have molecular basis of structure, metabolism, and function. The inner space of cells is divided into separate structured blocks that perform various functions. The nucleus, as the place where the genome is located, is the dominant part of eukaryotic

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cell, controlling the two main universal directions of life through the processes of replication and transcription: (a) it ensures reproduction of all cells and living bodies, which guarantees the continuity of life; (b) it ensures the processes of development and existence of organisms. The cytoplasm, as the main part of the phenome, has a complex internal organization that ensures the synchronous, coordinated flow of hundreds of complex processes in various parts of the cell body. The structural organization and many functions of organelles, cells, tissues, and organs are provided for by the surface apparatus and biological membranes. Cells are complex engineering and technical microconstructions, built with high precision on the basis of physical and chemical laws. Individual cells, organelles, and macromolecules can exist and function for some time under artificial conditions outside bodies, but it is impossible to combine them again in a living cell. Neither the genome, nor its phenotypic framework separately possess an individual life. The latter appears only at the level of a monolithic organism. Cells perform several fundamentally important functions: (a) they contain individual life, (b) they pass it on to the next generation, (c) they form multicellular bodies, and (d) they constitute the planetary system of life. The right to a long happy life was granted to the cell by Nature in the form of a fine organization involving a minimum set of unique structures, namely, molecules of replicating nucleic acids and multifunctional proteins, which ensure the phenomenon of biocatalysis and the ability to manipulate information under unique physicochemical conditions of low temperature and liquid water. Hence, billions of years of multi-vector searching, numerous experiments, and much trial and error have produced many varieties of living cells, their derivatives, and systems with many unique and amazing properties.

Chapter 4

Multicellular Organisms

4.1 Cells and Multicellular Organisms The cell, as the backbone of life, is described in Sect. 1.13. It is a standard unit of organization of living bodies, a structural unit of multicellular organisms. The cell is an autonomous microsystem of selected molecules. It is a highly ordered, heterogeneous, open, non-equilibrium system that constantly works against its own thermal destruction. Cellular macromolecules form a variety of complexes that possess qualitatively new properties and are capable of performing various functions. Cells are extremely dynamic systems. Directed and controlled biochemical and biophysical processes occur constantly in all parts and organelles of the cell. Various biochemical and biophysical processes take place in cellular complexes depending on their molecular composition and degree of orderliness. These processes are primarily aimed at transformation and targeted application of matter and energy for maintenance of their own complicated structural and functional organization, and only then at performing the functions of an organ or a whole organism. The organization and control of the high degree of order and functioning of cells is implemented by the genome. It is the genome which is the cause and if need be the remedy when it comes to organizing matter in a certain microspace. The genome builds a system of protection and life support around itself in the form of a cell to maintain its own homeostasis, self-preservation, reproduction, and distribution. From this point of view, a cell is a receptacle for the genome, possessing a set of properties and functions for its successful existence and reproduction. Using the information in the genome, an intermediary is built between it and an unfavorable external environment. Thus, as cells are crucially dependent on the genome, they are not entirely independent structures. The emergence of new cells and their differentiation, combinations, functioning, and death occur only on the basis of genetic information. Even when it is part of a tissue or an organ in a multicellular organism, each cell to a great extent lives its own life, since its organization and metabolism are aimed primarily at maintaining of its own homeostasis. This requires the greater part of the © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_4

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total energy consumption of the cell, while considerably less energy (depending on the specialization) is spent by the cell for the needs of an organ or an organism it is part of. Thus, multicellular organisms can be rightfully considered as highly complex communities of tiny living bodies, united for the purpose of their mutually beneficial existence. This is a qualitatively new state of existence of cells in a giant specialized colony. All cells act in concert, serve the interests of the organism, maintain its integrity, and provide for a variety of functions. The whole organism and all its interrelated constituent parts and cells are primarily regulated and directed by the genetic programs of its genome. Both an individual cell and a multicellular body may be referred to as an organism. An organism is a complexly organized unity. Both a cell and a multicellular organism meet this definition. They have many common principles of organization. However, in essence, these are completely different systems. Cells are a multi-heterogeneous unity of millions of kinds of molecules and their complexes, while multicellular organisms are systems consisting of fundamentally identical macrostructural functional units. The system of a multicellular organism implements the principle of using differentiated cells as integral blocks to form a new level of histological and anatomical structures, as well as functional complexes of considerable size. That is, on the one hand, multicellular organisms are arranged in a simpler way, since they are derivatives of interacting cells, and on the other hand, they are much more intricate, since they combine several levels of complexity. In addition, multicellular organisms involve different kinds of substances and systems which are derived from cells and perform auxiliary functions. Glycocalyx, body fluids, bones, hair, and so on are among the examples. Numerous organs and tissues of multicellular organisms perform general functions associated with survival and reproduction, mainly of the organisms themselves. Neuroendocrine and immune systems serve as additional tools that organize and control the structure and functions of multicellular organisms by integrating cells, tissues, and organs into a single organism. Based on the notion that cells are above all the receptacles of the genome, multicellular organisms can be considered as differentiated colonies of cells incubating individual genomes. Multicellular organisms are complex systems of various cells of the same genome, united into a single multicomponent body. Many groups of cells are differentiated, that is, they have a specific structure and are specialized to perform certain functions. Differentiated cells can form tissues and organs. These cells unite for a mutually beneficial joint existence, survival, and reproduction. The systems regulating the multicellular organism, such as the nervous, endocrine, and immune systems, are also controlled by the genome. Thus, a differentiated multicellular organism is a product of the selectively expressed functional gene systems of relatively independent cells of various parts of the body. Since cells and multicellular organisms are, despite the analogy, completely different biological systems, the principles of their reproduction, development, maintenance of integrity, aging, and death differ somewhat. Cells reproduce by division, and many multicellular organisms are forced to form reproductive cells—spores and gametes. The development of unicellular organisms is basically reduced to growth,

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while in multicellular organisms this is a very complex multistage process. Maintenance of the integrity of single cells is based on molecular mechanisms, while in multicellular organisms it is additionally regulated by a variety of cytological and physiological processes. Cell aging is caused by intracellular molecular processes, whereas in multicellular organisms, it is also very likely associated with the disturbance of regulation, control, and coordination of functioning of cells, tissues, and organs and their systems (see Chap. 11). There is always a corpse after the death of a multicellular body, while the decease of a unicellular organism is not always associated with an actual death, but may be due to termination of the existence of the maternal organism and emergence of two new ones as a result of division. Thus, it is not always possible to extrapolate the principles of the structure, functions, and behavior of individual cells to multicellular organisms and vice versa.

4.2 A Living Organism is the Phenotypic Framework of Its Genome The term “life” is always associated with the presence of certain bodies. It really is. Life cannot exist by itself without certain carriers. They are called living bodies, organisms, or individuals. A living organism is no longer an abstract concept, but a concrete one. It is a material body. It is the elementary unit of biological activity, the carrier of life. Each organism has its own special, personal characteristics, i.e., individuality, therefore it is called an individual. This is the original, complex organizational unit of the species, which has all the properties of the living. An individual is a representative of a certain species, a separate organism that possesses the peculiarities of the allelic composition of the genome, and as a result, certain peculiarities of the phenome. All individuals are genetically programmed for behaviors that ensure their survival. This is necessary to preserve every unit of life that contains a precious genome. Hence, the life strategy of any individual is survival, reproduction, and distribution of genomes. Organisms are extremely diverse in their nature, shape, and size. Bodies can be unicellular, multicellular, and also non-cellular. Sizes can range from nanometers (viruses) to tens of meters (blue whale, large plants). In shape, the bodies of unicellular organisms can be spherical (cocci), cylindrical (bacilli), spiral (spirilla), drop-shaped (mycoplasma), stellate, and even three- and four-angular. Single-celled eukaryotes are even more diverse and use almost all geometric shapes with various outgrowths that provide for active movement and protection. Multicellular organisms have monomeric or metameric bodies. Their shape is predetermined by the peculiarities of movement or, on the contrary, fixation in the substrate, leading to a wide range of forms (see Fig. 4.1). They can swim, fly, or run, and they can live in water, on land, or in the lithosphere. They got that way as a result of a long evolution and adaptation to specific conditions of existence, as well as to each other. But these are all living bodies,

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Fig. 4.1 Examples of different phenomes of animals. Despite such clear differences, they are unified by the presence of their genetic apparatus and cellular structure. All of them are products of cellular activity guided by their genomes. The peculiarities of their sizes, shapes, and contents are determined by their distinct genome

organisms with common properties and characteristics. All of them are relatively independent of the external environment from which they are separated by various membranes. All are autonomous and have a genotype and a phenotype. All of them are mortal, but capable of reproduction. On this basis, biological species can maintain the peculiarities of their organization for millions of years and trillions of generations. The non-cellular matter is of no less importance for the life of multicellular organisms. Its mass can even significantly exceed the mass of the cells. Among examples are the skeleton and intercellular fluid in mammals, tree trunks and branches, coral colonies, beetle integuments, and much more. This illustrates the importance of not only the cellular, but also the non-cellular surroundings of genomes. Organisms are a part of Nature and exist as one with their environment. They are characterized by special interactions with the environment in the form of exchange of matter and energy. These are interrelated processes, since the chemical energy is transferred with the flow of organic compounds. In this way, living beings create order and maintain homeostasis. Living bodies pump enormous amounts of external matter and energy through themselves. For example, an adult weighing 70 kg, consuming about 3 kg of food per day, and rejecting the same amount of waste, passes around 70,000 kg of matter through himself during his 70 years of life! Living bodies are characterized by high degrees of structural and functional order. Organisms develop, function, and maintain order thanks to the myriad molecular and cytogenetic processes that occur every second in cells. From this point of view, living bodies are “structured processes”. The high degree of structural orderliness is a type of information necessary for ordering various kinds of motion of matter at different levels of organization in living bodies (see Chap. 18).

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The enormous diversity of phenotypes of living bodies of various species is determined by an equally large number of genome variations. Implementation of different genetic information in the development process produces all this variability in living bodies. Living organisms are fundamentally different from inanimate objects in Nature, and from our own machines and complex constructions, in that they possess not only their special structures and functions in the form of a phenome, but also programs in the form of a genome for generating and organizing the same complex organisms. Moreover, these programs can be repeatedly duplicated (DNA replication) and transmitted from generation to generation in the process of reproduction. Even the most complex programmed robots created by ourselves, as well as computers and their systems that perform functions beyond human capabilities, do not contain programs for their own reproduction and development. Living bodies have a determined lifespan (see Chap. 11). In the process of existence, they gradually wear out, age, and then die. However, most individuals leave offspring behind, which ensures the genetic continuity of life for a given species (see Chap. 9). Actually, the main purpose of sexually reproducing organisms includes the following: (a) creating the necessary conditions for generation of germ cells; (b) direct production of gametes containing a permanent genome; (c) transfer of the genome to the next generation. Gamete bodies are a transitory form of life comprising the discrete genome of a given individual. This is a special form of the existence of life, which has fundamentally similar bodies and mechanisms for the vast majority of organisms that reproduce sexually. It is a form of existence of a genome without a true phenome. Thus, it should be emphasized that a living body is just one of the stages of the continuous life process of the genome, a process consisting of alternating forms of existence of gametes and their producers (Fig. 10.1). It is the genomes that create around themselves “phenotypic frameworks” as intermediaries for communication with the external environment, as well as the conditions necessary for their own survival and reproduction. This statement is also relevant for organisms that reproduce asexually. Thus, cells or complex organisms can also be considered as receptacles for the genome, as complex systems with a set of properties and functions for its successful existence and reproduction. The genome, in turn, is also a complex system that provides for many aspects of the life of the associated organism. That is, living bodies are entirely dependent on the genome, just as the genome depends on them. New cells and organisms, as well as their differentiation and functioning, emerge on the basis of genetic information in the genome. A phenotypic mediator between the genome and the external environment is created.

4.3 Summary A multicellular living organism is a complex system consisting of various cells of a single species of genome, united into a single multicomponent body. All cells possess special structure and specific functions. Uniting in different combinations, these

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cells can form tissues and organs. That is, a multicellular organism is a product of a selectively expressed genome of relatively independent cells in various parts of the body. Living bodies are the phenotypic framework of their genome. These are two mutually integrated, interdependent systems, which form a monolithic living body (see Sect. 2.6).

Chapter 5

General Characteristics of Living Bodies

5.1 Principles of Organization of Living Bodies Only unicellular and multicellular organisms, which were briefly described in the previous chapters, are the genuine representatives of living bodies. All of them possess universal principles of organization that distinguish them from the total mass of physical bodies. Autonomy. The most important organizational basis for the existence of living bodies is the principle of physical autonomy, which manifests itself in the isolation of their contents from the external environment. That is, they are organizationally closed. The necessary controlled purposeful processes can only occur in a restricted space of organized molecular systems with a special qualitative and quantitative composition. Autonomy is the relative independence of living bodies from the external environment. That is, an organism can exist in the surrounding space for a long period of time as a separate physical body. Bioautonomy. It should be noted that organisms possess not only physical autonomy, as physical bodies isolated from the external environment, but also biological autonomy. Bioautonomy is the ability of organisms to solve many life problems of existence and survival independently. In particular, living bodies provide themselves with metabolites and energy, support micro- and macro-organization, interact with the external environment, and regularly reproduce. However, not a single cell and not a single living body is completely autonomous. All organisms are open systems, which continuously exchange matter and energy with the external environment, and in the end are part of a single Nature (see Sect. 5.6). Interaction with the external environment. Despite the autonomy, the constant interaction of organisms with the external environment is maintained through the exchange of substances, energy, and information. Such an interaction is required due to the constant targeted consumption of matter and free energy for self-preservation, reproduction, and development (see Chap. 6). Discreteness is the intermittency in the organization of material bodies and their systems. Discreteness of the structure of living bodies means that, as systems, they © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_5

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consist of many separate, complex, interconnected, and interacting parts. Discreteness is a very important characteristic of a living system, as it provides internal movement and interaction of its parts, and thus manifestations of its various qualities, properties, and functions. Integrity. An organism is a standalone complex system consisting of many processes, subsystems, blocks, complexes, and molecules. All elements of living systems are ordered, interrelated, and interdependent, which leads to a qualitatively new result—the appearance of integrity. Based on this, the functions and behavior of biological bodies are mainly conditioned by internal processes. They move and perform work, not under the action of external forces, but on the basis of internal reactions to external influences or on the basis of internal stimuli. As a single whole, they react to various stimuli, move, and reproduce, while manifesting a standard set of biochemical reactions and the identity of various functions. Their integrity is stipulated by the strict hierarchy of construction, integration, and coordination of all components of living systems, which is regulated by the genome (see Sect. 12.1.1). The informational material principle. We believe that one of the basic organizational principles of living organisms is the unity of the interacting genome and phenome in one body. That is, any organism is both a genetic program and its final product in the form of a certain material body. Absolutely all aspects of the organization and functioning of living bodies are determined by special transformations of substances and energy directed by the genome (see Chaps. 13 and 14). The principle of self-reproduction. All living bodies are mortal, but they necessarily have the potential to reproduce their own kind, thanks to the fact that their genomes are capable of replication (see Chap. 9). Systemic principle. The organization of all known forms of life is based on highly ordered aqueous systems of organic substances. All living organisms are open heterogeneous nonequilibrium systems, the properties of which depend on the qualitative and quantitative composition of their interacting elements. The importance of this principle of organization is associated with the emergence of completely new qualities and properties of such systems in comparison with the properties of the elements that make them up. Moreover, it leads to emergence of conditions for the formation of various combinations of interacting elements in order to perform numerous functions. The basis for the existence of living systems is hierarchy, total interconnection, and dynamism of their numerous structures and functions (see Sect. 1.10). The principle of orderliness is the consistent arrangement of material bodies in space. The importance of this characteristic for living systems is that only the necessary elements of the system appear in a specific place at a certain time. Their consistent arrangement and orderly interaction determine the appearance of qualitatively new properties of such systems. In particular, a variety of proteins, nucleic acids, amino acids, specific lipids, and various carbohydrates are concentrated in the microscopic volume of a cell, although virtually absent in the environment. Moreover, the molecules of these substances are ordered and organized within the cell, forming complex specialized structures. One of the basic principles of the existence of biological systems is orderly movement at all levels of organization (see Sects. 5.3–5.5).

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The principle of self-repair and maintenance of homeostasis. Living bodies possess self-repair and regeneration mechanisms, which maintain their integrity and homeostasis. That is, they have the ability to self-restore using internal forces and impulses using substances and energy from the external environment. Maintaining the structural and metabolic homeostasis of the system ensures the stability of physiological processes and the relative independence of organisms from the external environment. Self-repair processes and the integrity of biological systems are continually monitored by a constantly active genome (see Chap. 12). The principle of deterministic self-organization. Self-organization is the ability of organisms to independently form ordered systems with different levels of organization. For example, this could be the selective internal concentration of certain substances, their consistent distribution, and the formation of organelles, differentiated cells, tissues, and organs. Such an ordered structural system provides controlled biochemical and physiological processes that support metabolism and function. Deterministic self-organization is a special ordering of living bodies, which arises on the basis of the patterns of self-organization and genetic information. It is the genome-determined self-organization that is the basis for the formation of specific living bodies. In this case, information guides the processes of self-organization in a certain direction. Thus, the structure and functions of living bodies are primarily determined by the system’s own internal guidelines (see Sect. 2.4). The principle of complementarity of elements of biological systems lies in the mutual correspondence between macromolecules, metabolism, physiology, morphology, behavior, and environmental factors, as well as the interaction and interdependence between different species of living beings and their habitats. That is, any organism exhibits an astonishing degree of logic in the organization, structure, and functioning of all its organs, tissues, and body parts, as well as an incredible correspondence between the external and internal structures and the natural environment (see Sect. 5.3). The principle of dynamism. Life is not a stationary state, but a process. More precisely, it is a multitude of specially determined processes. These are constant interactions, continuous reactions, and a continuous change in the states of cellular organelles, cells, tissues, and organs. These are the processes of constant transformation of matter and energy, and transformation of the genome and genetic information. It is continuous development and evolution. It is constant reproduction and inevitable death. The internal contents of the cells are so discrete and dynamic that they can be considered not so much bodies as continuous processes. Thus, one of the key conditions for the existence of organisms is organized and ordered movement. Work is continuously performed on the basis of all types of movement, aimed at survival, functioning, and reproduction. Moreover, the dynamics in living systems is nonlinear and allows the emergence of a new order at points of instability (see Sect. 5.2). The principle of selectivity. Cells contain only a limited number of genetically determined substances which participate in a limited set of biochemical reactions. There are only a few thousand varieties out of millions of possibilities. The selectivity of processes is regulated by a special set of enzymes that carry out only their inherent reactions. Only genetically determined and specifically located enzyme molecules

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can ensure the limited set of incredible biochemical reactions and physiological processes, based on catalysis, that organize and determine life (see Sect. 5.4). The principle of counteracting entropy. Most of the energy received from constantly occurring biochemical, biophysical, and physiological processes is directed against the internal and external forces of dissipation. This is the basis for creating and maintaining the organization of living bodies. This temporarily compensates for dissipation and balances the disturbing forces of nature, thereby ensuring the survival of organisms. Only the constant counteraction by individuals of the steady increase in entropy can sustain life (see Sect. 7.4, Part 12). None of these principles are decisive. Only their sum makes the physical body alive. A living organism emerges as a result of all these principles of organization. “Organization” and “organism” are cognate words, with “organization” being the root. That is, the name we use for a living body, “organism”, actually contains its main feature, namely, organization. An organism is a discrete complex system consisting of many subsystems and blocks. All elements of the system are interdependent and interconnected. Such a system is a complexly organized unity.

5.2 Motion and Activity Material bodies and their systems, from elementary particles to galaxies, are in constant motion. Motion is an inseparable property of matter (Fig. 5.1). Several basic forms of motion are distinguished in nature. In particular, mechanical motion is the spatial movement of bodies or their parts (including vibrations and rotation); physical motion includes electromagnetism, gravity, thermal motion, and the like; chemical motion consists of a variety of chemical reactions and interactions. The listed forms of motion are of great importance for living bodies, since they

Fig. 5.1 Motion and life are inseparable. 1—The primary energetic impulse led to the simultaneous emergence of motion and matter. 2—A subsequent informational impulse singled out a special form of motion from chaotic matter. Islands of ordered motion have emerged on the basis of the information programs in the genome. Thus, life arose on the basis of ordered thermal motion

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ensure all types of interactions, as well as metabolic, physiological, and behavioral processes. As a result, a new form of motion appears—biological motion. What is more, many properties of living organisms are determined by the motion of non-living components of the body. Moving a mass over a distance requires energy. Therefore, all types of motion in living systems are energy dependent, except for spontaneously occurring processes that increase entropy. In relation to living bodies, the processes of motion must be considered at several levels. 1. Movement of the organism as a single system. For individuals, this is essential for finding food and favorable living conditions, while avoiding unfavorable conditions, but also for finding a sexual partner and spreading into new territories. In the process of evolution, for the purpose of movement, organisms have developed a range of special locomotion organs: pseudopodia, cilia, flagella, membranes, legs, wings, fins, and so on. Many have developed a skeleton and a muscular system that sets the limbs in motion. All living organisms tend to spread into the surrounding environment. Spreading is the gradual dispersal of organisms over vast areas, investing hitherto undeveloped territories and ecological niches. This process is one of the main characteristics of the living. At the heart of this phenomenon are progressive reproduction, an increase in the number of populations, the movement of individuals, and the process of adaptation of organisms to new environmental conditions. All organisms are genetically predisposed to spread. Spreading is one of the instincts associated with the desire to have sources of food (matter and energy), and also areas for reproduction and habitation. The basis of spreading is movement. Behavior is a conditioned, purposeful, and controlled movement. The behavior of living bodies is based on a variety of reflexes and instincts. The elementary acts of reflex behavior are various taxis (directed movements under the influence of a stimulus and internal impulse), which already appear in unicellular creatures. Animals have complex types of behavioral motion, which, however, are also the result of internal motivation and influenced by external and internal signals. In turn, the wide variety of reactions to stimuli is determined by the specificity of the genetic programs characteristic of a given type of genome. These programs condition the characteristics of behavior. 2. Movement of body parts. Animals have the ability to move certain parts of the body selectively. This enables complex behavioral processes. For example, the pursuit of prey by a predator, its capture, neutralization, and devouring require fine coordination of movements of various parts of the body. The coordination of movements of body parts is carried out by the nervous system. 3. Movement of body fluids. The flow of blood and lymph in animals enables the movement of nutrient molecules, oxygen, carbon dioxide, erythrocytes, leukocytes, and others. This ensures metabolism, cellular respiration, and the body’s immune defenses.

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4. Cell movement. Multicellular organisms contain free-living cells that do not have constant localization and are capable of passive or active movement. For example, erythrocytes, platelets, and leukocytes move passively with the blood flow. Some lymphocytes, macrophages, and neuroglial cells are capable of active independent movement. They are able to form pseudopodia and perform amoeboid movements. Therefore, they can “crawl out” of blood vessels, “crawl” into tissues, and move towards foreign bodies to neutralize them. The ability of sperm to move in a liquid medium ensures the processes of insemination and fertilization, and hence the very phenomenon of reproduction. Unicellular organisms, living freely in nature as individual cells, are able to move actively with application of special mechanisms. For example, (a) using pseudopodia, (amoeba); (b) using flagella (euglena green, lamblia); (c) using special outgrowths of the cytoplasm—undulating membranes (trypanosomes, leishmania); (d) using cilia (ciliate shoe). 5. Migration of individual cells and cell populations. Cell migration is very important in the early stages of embryogenesis. Individual cells of different parts of the embryo can migrate to other parts (over a fairly considerable distance) and form a specific population, which then gives rise to an organ. For example, cells of the neural crests of the neurula of an early embryo are capable of extensive, consistent migrations throughout the embryo. Some of them are included in the skin, others move inward and form spinal ganglia, nerve nodes, and so on. The process of differentiation of migrating cells is controlled by their cellular microenvironment. During embryogenesis, cells do not move chaotically, but in a strictly ordered manner. Germ layers with specific structure and spatial arrangement are formed this way during gastrulation. The reason for the movement of migrating cells in a certain direction is chemotaxis. In addition, cells perceive the microstructure of the environment and move along certain structures. The processes of cellular recognition and adhesion give rise to a certain structural and functional reorganization, guide the movement of the cells, and halt them at a certain spot. Embryonic mesenchymal cells migrate individually or in small groups. They move by means of amoeboid movements. Epithelial cells (singlelayer groups of cells in close contact with each other) usually move as a whole layer. 6. Transport of substances in the organism. To ensure metabolism and various functions, a variety of substances must be move around within the body. In particular, nutrients must be transferred from the digestive tract to the cells of various organs and tissues. A variety of membrane and cellular mechanisms serve to transport certain molecules across diverse membranes and cells. They play a connecting role between the different parts of the cells and the body in which interrelated processes take place. 7. Movement of components of the cytoplasm. All components of the cytoplasm are in constant motion. The main types of molecular motion are: (a) thermal motion; (b) diffusion; and (c) directed motion of molecules in water channels along microtubules. This ensures that the right molecules end up in the right place at the right

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time, and this in turn ensures the flow of thousands of biochemical processes involved in the cellular metabolism. Each cytosol molecule can experience thousands of collisions per second with other molecules. The colloidal content of the cytosol can pass from the liquid state or sol to the more solid state or gel, and vice versa, which also regulates the intensity of motion of the molecules of the cytoplasm and its organelles. Vesicles and organelles can move through the cytoplasm with the help of special mobile proteins and cytoskeleton fibrils. The cytoskeleton can change the shape of cells and participate in the formation of outgrowths on the cytoplasmic membrane. Thus, the cytosol in cells has a precise, ordered, colloidal structure, where enzymes of certain biochemical processes are fixed at certain sites, and the necessary substances move to them along specialized “molecular paths”. 8. Motion of molecules and atoms. Each molecule in a biosystem carries out several types of thermal motion, in particular, reciprocating, rotational, and individual fluctuations. Brownian motion is the basis of life, as it provides contact and interaction between molecules in cells, and this concerns all biochemical metabolic processes. Any biochemical reactions are also a combination of molecular and atomic dynamic processes that are ensured by various types of motion. For example, when the substrate molecule arrives in the active site of the enzyme, this causes the movement of its polypeptide chains, thus changing its conformation. In this case, the molecules of substrates move and orient themselves in a certain way in the active site of the enzyme. The atoms of the functional groups of the enzyme and substrates interact with each other, which causes some to break and other chemical bonds to form, resulting in new products. Along with this, protons, electrons, methyl-, acetyl-, hydroxyl-, and other functional groups move from one molecule to another. Then the enzyme again changes its structure due to the motion of polypeptide chains, the active site opens, and the reaction products are released into the environment. After that, the enzyme once again acquires its original conformation. The above processes are repeated many times. Their rates are extremely high, up to thousands of transformations per second. All of these are examples of molecular and intramolecular types of motion that provide for a variety of vital processes, from metabolism to physiological activity and behavioral reactions of the whole organism. Thus, orderly motion at all levels of organization of biological systems is one of the main conditions for the course of life processes, as well as for the existence and survival of organisms. And the orderliness of the structure of living bodies is necessary for the isolation and organization of these motion processes, which run against the action of the disintegrating forces exerted by the external and internal environments. That is, constant activity is manifested and work is continuously performed on the basis of all types of motion, directed against unfavorable factors that would otherwise increase entropy.

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5.3 Biological Expediency Living bodies are designed very logically and expediently. Any organism shows amazing rationality in the organization, structure, and functioning of all parts of its body, as well as full compliance with the natural environment. The structure of vertebrates living in water is appropriate for this particular habitat. These organisms have gills, fins, a streamlined body, and much more. Birds adapted for flight have wings, highly acute vision, quick reactions, light bones, and so on. Single-celled organisms living in various conditions have different metabolisms, depending on the characteristics of nutrition and energy conversion. Biological expediency can be traced at all levels of organization of the living: 1. Molecular level. It turned out to be most expedient to use organic compounds for the organization of all kinds of biological structures. This is explained by the fact that only carbon has the property of forming an immense range of molecules, from very small to enormous molecular weights, with various functional groups. Most of these substances are readily soluble in water and can interact with each other. At the same time, from the countless number of organic compounds, natural selection has chosen a rather limited set of biomolecules. These include two dozen amino acids, some fatty acids, and a number of carbohydrates and nitrogenous bases, which are able to form macromolecules. Of these, only a limited number of possible variants of macromolecules corresponding to the vital properties were selected by the logic of the living, namely, certain proteins, nucleic acids, a number of carbohydrate polymers, and some groups of lipids. That is, the expediency of the selection of life molecules in the process of evolution is clearly traced. At this level, the rationality of the choice was ensured by the natural selection of stable complexes of protobionts that arose as a result of the interaction and aggregation of certain molecules. Countless other variants of molecular complexes were, most likely, simply less stable and hence quickly destroyed by environmental factors. 2. Cellular level. It is logical enough that cells should be the units of life and structural units of multicellular organisms. The most stable protobionts surrounded by a membrane were selected by environmental conditions. They were isolated from the actions of various environmental factors by the phospholipid membrane, and so became much more stable and safer. The necessary macromolecules, capable of controlled interaction and the creation of order, are concentrated in a small membrane-limited aqueous space. The expediency of small cell sizes is due to the fact that the interconnected coordinated course of instant biochemical reactions based on thermal motion and diffusion of molecules is only possible in such microvolumes. The spherical shape of free-living cells is also highly expedient, since it provides the maximum surface area of contact and interaction with molecules of the external environment. The cells in organs and tissues also have perfectly logical shapes and sizes, corresponding to the peculiarities of the structure and function of each part of the body.

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The cellular level of expediency is provided by the laws of chemistry and physics, adaptation and natural selection. Many variants of poorly adapted cells and their complexes were simply eliminated by environmental factors. 3. Organism. Single-celled organisms are intelligently arranged in relation to their needs and habitat. They are adapted. In this case, they developed along a path which saw the emergence of individual cells with numerous complex organelles, the functions of which resemble, albeit in a simplified form, certain organs and functions of higher organisms. For example, the tiny, refined, complex unicellular creature Paramecium caudatum, in addition to other organelles commonly found in eukaryotes, also has: (a) a network of cytoplasmic fibers that coordinate the beating of cilia and can even change the direction of their beating; (b) a specialized organ for swallowing food (oral cavity and pharynx); (c) organelles for digestion (food vacuoles); (d) an organelle for excretion of solid particles (cytoproct); (e) two “kidneys” for excretion of fluid (contractile vacuoles); (f) somatic DNA (macro-nucleus), which carries information for protein synthesis; g) hereditary DNA (one or more micronuclei) responsible for replication and reproduction; h) a defensive apparatus (trichocyst), consisting of tiny needles, with which this tiny unicellular creature shoots at its enemies. All this is extremely rational and expedient from the point of view of the need to solve strategies of survival and reproduction under certain environmental conditions. The expediency of building large organisms from cells is associated above all with the convenience of constructing organs and body parts of various shapes and contents from standard discrete units. In addition, only cells possess the properties of storing and transmitting genetic information, and only cells are capable of converting energy and using it to maintain their own structure for a long time. The specialization of cells in multicellular organisms has provided ample opportunities for the development and adaptation of organisms. In this way, cells formed tissues and organs, which provided a variety of functions for multicellular organisms. Cellular organization contributes to the constant replacement of dying body parts (cell groups) without harm to the body. Cellular structure enables maintenance of molecular control and regulation of even the tiniest part of a large multicellular organism. The expediency of the anatomical and physiological organization of complex organisms should also be noted. For example, all mammals have upper and lower body parts, with only the lower part having limbs. Their localization is due to gravity and the need to raise the body above the ground for its movement. Mammals have anterior and posterior body parts. At the front is the head, most sensors, and the brain, where different forms of information are perceived and immediately processed. All mammals have a standard set of organs and tissues located in strictly defined parts of the body. These organs perform the same vital functions across all species. Their structure, localization, and regulation have been carefully developed on the basis of the programs inherent in the global genome, precisely reiterating outlines of the complexes with similar functions throughout all levels of the living, and refined by natural selection in the process of adaptation and evolution over many millions of years.

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Mutation, recombination, transgenesis, and hybridization of genetic material brought about new variants of the genotypes of organisms. As a result, many new variants of phenotypes appeared, but only those that were the best adapted to the existing environmental factors have survived and left behind any offspring. The rest of the phenotypes did not pass the “filter” of the natural selection. At certain times, they no longer survived long enough to reproduce or did not produce viable progeny, even though many of them were perfectly well adapted at some previous time in the development of the phenomenon of life and were a necessary part of the global phenome at that stage of evolution. The expediency of all properties of cells and organisms is due to the need to solve the main strategic tasks of life: survival, reproduction, and distribution. The expediency of the structure, functions, and behavior of organisms came about as a result of the evolution and long-term natural selection of individuals with properties and characteristics that ensured their stable existence and reproduction. All living beings are incredibly complete organisms. Regardless of the level of organization and complexity of their structure, unicellular organisms, jellyfish, worms, amphibians, and mammals are very expediently constructed and perfectly adapted to the relevant habitat, despite the enormous differences in the amounts and quality of genetic material. The difference appears only in the size and complexity of the body structure, but not in the ability to adapt, survive, and reproduce. All of them possess absolutely all the necessary processes and functions essential for survival under the conditions of their given habitat. That is, every genome is complete and perfect in relation to the phenome it creates, which is in turn absolutely sufficient to support its own life and its own genome.

5.4 Biological Versatility Chemical versatility. The chemical composition of living things is rather uniform. Out of the hundreds of elements existing in nature, the basis of organisms (99%) is composed of only six: C, H, O, N, S, P. A few more, including Na, K, Cl, Ca, Mg, Fe, Co, Zn, Mn, and several others, play an auxiliary role in a number of biochemical processes. Polyatomic carbon compounds of organic substances constitute the backbone in the organization of any living body. Certain combinations of atoms can be repeated many times in them, including methyl—CH3 , hydroxyl—OH, carboxyl— COOH, amino groups—NH2 , and some others. Each of these functional groups has a standard set of chemical properties. Biochemical versatility. Of the innumerable set of organic molecules, living systems contain only a limited set of substrates. This is a standard set of 20 αamino acids (out of hundreds possible), several hexoses, pentoses, and trioses (out of thousands possible), several carboxylic acids (out of thousands existing in nature), several derivatives of purine and pyrimidine bases, and several steroids. The optical asymmetry of metabolically active molecules is a distinctive feature of the chemical composition of living organisms. It is represented in living objects by levorotatory

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or dextrorotatory forms. All living organisms contain the same forms of optical and geometric isomers. In particular, all have L-amino acids, but not D-amino acids; D-glucose, but not L-glucose; fumaric, but not maleic acid, etc. Living nature exploits only a limited number of cofactors of enzymes: NAD, FAD, HS-CoA, lipoic acid, coenzyme Q, biotin, and some others. The main energetic mediator in all cells is ATP. Just four main groups of macromolecules are formed from the standard set of low-molecular-weight precursors (amino acids, nucleotides, monosaccharides, and carboxylic acids). These are proteins, nucleic acids, polysaccharides, and lipids. The numerous structural proteins and enzymes are very similar in the cells of different organisms. Polysaccharides are represented everywhere mainly by polymers of glucose: glycogen, starch, and cellulose. There are only two types of nucleic acid across all species of organisms: DNA and RNA, assembled from just five nucleotides, the same for all living organisms. Living nature also uses a rather limited number of metabolic pathways. Moreover, most of them are standard for an overwhelming number of organisms. These include fermentation, glycolysis, the citric acid cycle, the mitochondrial respiratory chain, ATP synthesis, protein synthesis, β-oxidation of fatty acids, and some others. The same metabolic pathways are maintained by hundreds of the same enzymes. A surprisingly small set of regulatory molecules is used by nature out of millions of possible variants. For example, there is a standard set of hormones, typical for all chordates. Growth hormone has virtually the same molecular structure in fish and in mammals. Insulin, a glucose regulator that acts on specific membrane receptors, is identical in many species of animals. Neurotransmitters, the molecules secreted in the nerve endings of all animals, have a very small set of variations out of a huge number of possibilities. These are adrenaline, norepinephrine, acetylcholine, and a few others. All chemical transformations in living organisms obey the principle of structural complementarity. Biochemical reactions in living systems are characterized by the desire to avoid the production of by-products, while the end products of reactions are generally used in others, forming a variety of widely branched, interconnected metabolic chains. The principle of structural complementarity dictates the use of standard enzymes, standard processes, and standard molecules in most biological systems. Thus, all cells in the various kingdoms of living organisms have a similar molecular organization and a universal system of biochemical transformations. Morphological universality. Living organisms have clear standards in their structure, both at the level of cells and at the level of the whole organism. The cells of all the kingdoms of organisms have a single principle of organization: they have a genome, a surface apparatus that surrounds a cell, and a cytoplasm saturated with enzymes. Cells are small objects, on average ranging between 1 and 100 μm in diameter (with some exceptions). They have essentially the same molecular composition (mainly consisting of H2 O, anions and cations, proteins, nucleic acids, lipids, and carbohydrates). All cells are enclosed in biological membranes that have a single principle of organization and are built of almost identical molecules. Eukaryotic cells are separated by inner membranes into compartments. Organelles in many thousands

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of types of cells share the same principle of organization. Mitochondria, endoplasmic reticulum, nucleus, lysosomes, ribosomes, and other organelles differ only in minor structural details. We may conclude that the appearance of a universal cell many millions of years ago as a result of the evolution of protobionts revealed the standard unit of organization of living bodies. Multicellular organisms also have certain standards of morphological organization, although organisms of different kingdoms, types, and classes can differ significantly. For example, mammals have much in common, despite their great diversity: a single principle of skeletal organization, the presence of similar organs and tissues, the presence of five-digit limbs, similar organs of vision and hearing, and much more. Higher plants also possess generative and vegetative organs composed of standard cells and tissues. Vegetative organs are represented by roots, stems, leaves, and their various modifications. Physiological versatility. This is inherent both in the various cells of organisms and in the organs, tissues, and body parts of many different organisms of a single kingdom. The role of cellular membranes in selective transport of molecules are based on the same principle and differ only in the details. The principle of contraction of muscle cells has a single actomyosin basis. Mechanisms of secretion barely differ in the cells of diverse animals. The principles of phagocytosis, used by certain primitive unicellular organisms, are also used by leukocytes in complex multicellular organisms. Intracellular digestion by hydrolytic enzymes emerged in early unicellular organisms, and the same principle operates in all modern living organisms. The principles of digestion are the same for all animals with a digestive system. Motion is provided by muscles attached to the skeleton. Reflex-based neural regulation is characteristic of most highly organized animals. The endocrine system of chordates has essentially the same organization and a standard set of hormones with the same mechanism of action. Biophysical and physiological mechanisms of sight and hearing are universal among all vertebrate organisms, with some minor peculiarities. Their circulatory system is based on fundamentally the same structure and principles of functioning. The overwhelming majority of living organisms breathe oxygen from the air, soil, or water. Terrestrial creatures have very similar respiratory organs and principles of consumption, and use oxygen in similar ways. The cytogenetic and physiological mechanisms of sexual reproduction are also very similar in all organisms. They are based on the processes of replication, meiosis, gametogenesis, fertilization, and embryonic development. Genetic versatility. The genetic material of all organisms is, without exception, represented by nucleic acids that have a single principle of organization and identical properties and functions. Only two groups of these macromolecules are known: DNA and RNA. Moreover, RNA has three main types: mRNA, tRNA, and rRNA, which are characteristic of cells across all kingdoms of organisms. These macromolecules vary in different organisms only in the sequence of standard nucleotides. Individual hereditary information is recorded with a specific sequence of nucleotides using a universal genetic code. The unit of hereditary information is the gene. The mechanisms of gene expression are identical in all living beings: transcription followed by translation. The processes of synthesis of RNA and proteins, as well as most of

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the enzymes in these reactions, are the same for all. The integration and regulation center of all living bodies is the genome. All types of reproduction known in nature are based on the universal molecular mechanism of DNA replication. The doubled genetic material is then divided between the daughter cells of any organism by the standard, very complex, evolutionarily ancient mechanisms of mitosis or meiosis. And the genome continues its existence in a new bodily framework or phenotype (see Chap. 9). All the facts presented above testify to a single molecular and biochemical basis of all living beings, and the unity of morphological and physiological principles in the organization of the entire range of living organisms. This attests to the close relationship between all living entities, their emergence from a single source, and the existence of the phenomenon of life as a single global system.

5.5 Fractality Fractality is the use of a single principle of organization at various structural levels. In a broader sense, we can talk about structural–functional fractality. In this sense, any multicellular organism is fractal, as it consists of cells functionally similar to it. The unity of the principles of organization of living bodies is due to natural selection of the most favorable combinations of molecules and their complexes, the choice of the most thermodynamically and economically beneficial biochemical processes, and selection of the optimal forms of structure, principles of interaction with the environment, and so on. The effect of a number of constant environmental factors, such as gravity, photoperiodism, electromagnetic radiation, aquatic environment, temperature, and so on, is an important aspect in the selection of fractal principles for the organization of biological systems. Given the above-mentioned factors, nature applied optimal organization algorithms based on the principles of similarity. This is evidenced by the presence of widespread similarity at all levels of the evolutionary hierarchy of organisms, as manifested in similar patterns of structural design, identical metabolic processes, similarity of functions, and the same mechanisms for maintaining orderliness. The phenomenon of similarity in evolutionary biology is reflected in the concepts of homology and analogy of structures. Homologous structures have a common genealogical basis, but are capable of performing different functions (for example, the limbs of a human and a whale). Analogous structures, on the contrary, have a different genealogical basis and their similarity is due to the unity of the performed functions (for example, bird wings and insect wings). In this context, it should be emphasized that the genomes of all living organisms are homologous to each other, since, despite the variety of performed functions and certain variances, they have a single basis. At the same time, in a world where phenomes are subjected to environmental pressures, the phenomenon of analogy is widespread.

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Structural–functional similarity in nature is primarily determined by the use of the same limited, standard sets of molecules in all life forms. Successful combinations of monomers of organic substances and the formation of multifunctional polymers (nucleic acids and proteins) are characteristic of absolutely all living organisms. The presence of uniform membranes, the principle of compartmentalization of living bodies, and the principle of autonomy are inherent both in single cells and in multicellular organisms. The principles of recording, transfer, and realization of genetic information that arose billions of years ago are absolutely identical for all living beings. The principle whereby the phenotype is conditioned by the genotype underlies all living bodies. The highly regulated and controlled metabolism of all organisms is based on the principle of selective catalysis, and enzymes are the main “actors” of all micro- or macro-processes in different living systems. The identity of many molecular mechanisms and some functions has remained virtually unchanged at all levels of organization of living systems, from unicellular algae to modern mammals. For example, nearly identical carrier proteins are involved in electron transfer and oxidative phosphorylation systems. The structure and principles of functioning of the molecular machines called ribosomes are practically the same in all organisms. Polymers of glucose (glycogen and starch) are the main accumulators of energy for the majority of cells. Genetic similarity is determined by the presence of the genome in all living bodies, as custodian and operator of genetic information, as well as by the common principles and mechanisms used to implement information through RNA and proteins. The initial life form of living bodies as a spherical cavity is reproduced in one form or another at all stages of phylogenesis. The stable cavity structure, which turned out to be a successful solution at the level of protobionts and then at the level of a single cell, was also carried over by evolution to multicellular organisms. And the outer covers and internal cavities were constructed by biological systems from their own specialized cells. In this case, a cavity surrounded by a membrane and a compartment content served as a technological model that became the basis for constructing fractal spatial forms of self-organizing biosystems. The impact of gravity introduced polarity into the organization of living bodies, leading to the presence of upper and lower parts in most organisms. In animals, the lower part is a form of support or limbs, and in plants it is a variety of roots and means of attachment. Mobility determined the difference in the structure of the front and rear parts of animal bodies. Generally, systems for perceiving and processing information, as well as the organs involved in food intake, are concentrated in the front part, in the direction of motion, whereas the organs of reproduction and excretion are concentrated at the back. The principles of reproduction were “developed” by nature billions of years ago. The molecular mechanism of DNA replication lies at the heart of absolutely all modern forms and types of reproduction of representatives of all kingdoms of organisms. This is followed by the compaction of the genetic material, the formation of chromosomes, and their further distribution into daughter cells during mitosis.

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All types of sexual reproduction utilize a single principle of formation and fusion of the genome-containing gametes. The development of multicellular organisms is based on common mechanisms of determination, differential expression, division, differentiation, and growth of cells. All living organisms are material self-regulating cybernetic systems, constructed and functioning on the basis of information that they are able to perceive, process, and also exchange with other systems and the environment. These and many other fractal principles of organization in living bodies are characteristic of all existing organisms. From this point of view, the evolutionary process of the living can be represented as a constant selection of potentially useful forms, structures, combinations, principles, processes, and mechanisms, accumulated over a long period of time “waiting” for suitable conditions to be in demand.

5.6 Bioautonomy as the Basis for Independent Existence Bioautonomy is a special property of living bodies allowing them to solve many of life’s challenges of existence and survival independently. For example, they use their own means to provide themselves with substances and energy from the external environment, transform them for the own specific purposes, maintain their own levels of organization, regulate their own metabolism and functions, and multiply.

5.6.1 Self-Organization As one of the main characteristics of life, orderliness arose out of the chaos of the material world in a process of self-organization based on the physical and chemical laws of the interaction of molecules and their systems. Self-organization is the property of living bodies to form on their own ordered systems with different levels of organization based on their features and their own genetic programs. At the cellular level, this is a selective inner concentration of certain molecules, their directed distribution, the formation of organelles, and compartments saturated with specific enzymes. Such an ordered system of molecules and their complexes determines the course of controlled biochemical and biophysical processes which ensures metabolism and functions. The ability to self-organize is inherent not only in structures, but also in processes. In particular, self-sustaining non-equilibrium networks of enzymatic reactions form spontaneously in developing cells, develop through a feedback system, and form new kinds of organization. Deterministic self-organization is a specific orderliness and organization of organisms which arises on the basis of physicochemical laws and genetic information. Selforganization determined by the genome is the basis for the ordered structures and processes of living bodies. In this case, the information also determines the processes

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of self-organization and leads them in a certain direction. Thus, living systems are characterized by deterministic self-organization, as the self-construction of standard ordered structures and processes based on their own genetic information and physical mechanisms of self-organization. Cellular systems are characterized by a relatively stable state of elements, as well as stable resistance to aggressive environmental factors. This is possible if the binding forces between the elements of the system exceed the power of external environmental forces acting on the system. Cells and organisms prevent their own destruction by a system of constant recovery based on the flow of energy and matter from the outside, which is a necessary condition for the existence of a nonequilibrium system. If the system’s ability to self-organize and self-maintain its own structure weakens, for example, due to inadequate energy replenishment, then its elements become less organized and the system gradually collapses (the entropy increases). Living bodies are essentially highly organized formations that work to lower their own entropy by increasing the entropy of the environment. It is also assumed that an excess of free energy absorbed by an open system can contribute to its selfcomplexification. This means that living organisms in the process of development not only resist the growth of entropy and chaos, but also form increasingly complex structures through the use of energy, matter, and information. It is on this basis that the subsequent complexification and improvement of biological systems occurs. The main mechanisms of self-organization at all levels are the processes of interaction and association. For example, aggregation at the molecular level leads to the combination of individual units into groups and the formation of certain complexes of macromolecules (e.g., enzymatic complexes). It is known that amphipolar phospholipid molecules in an aqueous medium form ordered structures, prototypes of biomembranes. The unification of various organelles into systems and their genetically coordinated functioning determines the cellular level of organization of living beings. In turn, cells that are different in structure and function combine, interact with each other, and form functional units of tissues and organs. Thus, as determined by the genome, the self-organization of cells underlies the formation of the ordered structures and processes of living bodies (see also Sect. 2.4).

5.6.2 Self-Regulation Self-regulation is the property of organisms to independently and automatically control and maintain all the parameters of their internal homeostasis. This ensures long-term stable operation of all metabolic and functional systems. Any living body is an integral, complex system that exists in a stable state in the environment for a relatively long time, despite constant wear and degradation. Maintenance of its stable state and integrity ensures its survival and successful existence in an unstable environment. For example, cells are able to control and maintain all metabolic and physiological parameters within rather narrow limits for a fairly long time. Enzymes and

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biologically active molecules, information on the expression of which is contained in the DNA, precisely coordinate billions of simultaneous biochemical reactions in the cells. Various mechanisms (for example, involving hormones) regulate the activity of cellular enzymes when existing cellular conditions have to be changed. The most common form of enzyme regulation is readily reversible feedback inhibition, when the first enzyme of the metabolic pathway is affected by the end product of this pathway. Another regulatory pathway involves the chemical modification of one enzyme by another, often as a result of phosphorylation. A more extended form of metabolic regulation is the synthesis of special enzymes that include or alter metabolic pathways. Combinations of regulatory mechanisms can induce strong and lasting changes in cellular metabolism. Various biochemical reactions occur in different intracellular compartments. That is, the spatial delimitation of the cell by the inner membranes allows organelles to carry out additional regulation and specialization of their biochemical functions. Thus, evidently, the cell is an autonomous self-regulating system striving for genetically programmed support of its own structure and functions (see also Sect. 7.1).

5.6.3 Self-Preservation Self-preservation is the property of organisms to preserve their own structure, metabolism, and functions throughout life through protection against adverse factors and through constant self-repair. The cells of living organisms are characterized by a stable, highly ordered internal structure and dynamic constancy of structural and functional homeostatic parameters. These parameters are maintained in biosystems in spite of the constant action of disorganizing forces, such as, for example, constant thermal motion, various kinds of radiation, changes in pressure and pH, toxic effects of metabolites and singlet oxygen, mechanical action, and so on. Cells have a system of protection against adverse factors. In particular, cells contain special enzymes that detoxify atomic oxygen, hydrogen peroxide, and other hazardous metabolites. All cells have a system for excreting harmful metabolic products from the inner space to the outside. Protozoa possess taxis and are able to avoid the adverse effects of the external environment by purposeful movement. In addition, all cells work constantly against forces that seek to destroy their highly ordered system. To do this, they use free energy and matter, actively consumed from the external environment. On the basis of genetic programs, the consumed energy and matter are transformed and purposefully used to maintain autonomous parameters, as well as for development, functioning, and reproduction. In addition, a multitude of biochemical processes quite uncharacteristic of inanimate nature are ensured in cells. They are unique and proceed only under conditions of autonomous internal cell contents. Moreover, all chemical processes are strictly controlled and managed by the autonomous cellular genetic system. Based on this, the functions and behavior of cells are mainly determined by internal processes.

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5.6.4 Self-Repair Self-repair is the property of organisms to independently and continuously restore and renew damaged or worn out structures. Any living body is constantly exposed to all kinds of environmental factors. They could quickly perish if there were no special mechanisms for self-repair and maintenance of their integrity. These mechanisms work at all levels in the organization of an organism, renewing worn out structures and restoring functions. At the cellular level, there is a constant renewal of macromolecules and cell organelles. The lifetime of a protein molecule is on average 12–20 h. Worn out molecules are decomposed by proteases to amino acids, which then serve as building blocks for building new functionally active proteins. This process is extremely intense. In a few days, the protein composition of a human being almost completely changes, although there are certain proteins (collagen, elastin, and others) that can exist for years. Similar processes occur with other macromolecules and their complexes, and also with organelles. Constant DNA repair is provided for by molecular processes with immediate restoration of damaged segments by specialized enzymes. In addition, the preservation of an unchanged structure is facilitated by periodic replication processes that occur with DNA molecules each time the genetic material divides, followed by division of the cell. In the process of replication, enzymes control the integrity of nucleic acid molecules and “repair” them, if necessary. Constant repair of the cellular composition of tissues and organs in multicellular organisms is carried out by replacing damaged or worn out cells with new ones. The causes of damage are environmental factors, but also the accumulation of toxins or the action of toxic substances. Moreover, the lifespan of most cells is genetically determined. On average, mammalian cells live and function from several hours to many years. For example, in humans, the lifespan of neutrophils is less than 4 h, while brain cells can exist for 200 years plus. Worn out and damaged cells are eventually destroyed by the enzymes of their own lysosomes. They are fragmented and the fragments are absorbed by phagocytes. Perished cells are replaced by new functionally active cells that appear after division and differentiation of stem cells. Maintenance of integrity and orderliness consumes up to 90% of the energy produced by the body. An equally important condition for maintaining a high standard of integrity is the use of genetic information, which controls and regulates the generation of the necessary components of complex biological systems. The main molecular process which provides for all aspects of this maintenance is biological synthesis. Thus, the constant controlled renewal of the cellular composition of tissues and organs, various regeneration processes, and also the constant renewal of the molecular structure of cells are a key condition for the long life of organisms and maintenance of a high degree of orderliness and homeostasis. That is, cells and organisms engage in colossal internal dynamics to replace and maintain their constituent components against a background of constant composition, volume, and shape (see also Sect. 12.1.1).

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5.6.5 Self-Sufficiency Self-sufficiency is the ability of cells to independently provide themselves with the substances and energy necessary for life. All living organisms can be divided into groups according to the type of consumption of energy and carbon-containing substances. Of the many forms in which energy can exist, living bodies are only able to assimilate light energy and chemical energy. Phototrophs are organisms that synthesize all the organic substances they need using the energy of light. Organisms that use chemical energy for these purposes are chemotrophs. Cells of phototrophic organisms contain special molecules that capture the energy of light, whereas chemotrophic organisms do not have such molecules. Living bodies that consume inorganic carbon (CO2 ) are called autotrophs. Organisms that use an organic carbon source are called heterotrophs. Living organisms are classified according to four possible metabolic pathways, depending on the combination of pathways of energy and carbon consumption they use. Most representatives of the living world are photoautotrophs and chemoheterotrophs, while a few small groups of bacteria are chemoautotrophs and photoheterotrophs. Some organisms cannot be completely assigned to any of the groups. For example, the single celled Euglena or multicellular higher carnivorous plants can behave both as an autotroph and as a heterotroph. It should be noted that chemotrophic organisms are completely dependent on phototrophic ones for their supply of energy, whereas heterotrophic organisms are entirely dependent on autotrophs for the supply of carbon compounds. However, absolutely all organisms are able to provide themselves with both substances and energy, completely independently and selectively, using environmental factors (see also Chap. 6).

5.6.6 Self-Reproduction This key property of living bodies is described in detail in Chap. 9. It is the ability of living bodies to independently produce homologous genomes and living bodies. Self-reproduction is based on the copying and cloning of macromolecules, ordered and organized structures, systems, and processes, based on the processes of replication, transcription, translation, and expression (see Chap. 14). The ability to “copy one’s own kind” ensures the infinite preservation across time and space of the main evolutionary achievements, as well as multiple, very fast and accurate reproduction of typical biological structures and functions that are of decisive importance for life.

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5.6.7 Self-Construction This is the ability of living bodies to independently build a standard, complex, architecturally isolated system that constitutes a whole organism on the basis of internal information, with programmed consistency. This property is no less important than self-reproduction, since it is not enough just to produce two identical daughter genomes, which is exactly the essence of self-reproduction. The copies must also grow, differentiate, and develop into a multicellular organism of a particular biological species. Self-construction comes, so to speak, from the inside. This corresponds to the terms growth and development, which refer to the development of living bodies in the process of ontogenesis. These properties are described in Chap. 10. It should be noted that all the abilities listed above, which allow a living form to independently solve the numerous problems of existence, result from the intrinsic motivation of genomes for self-preservation.

5.6.8 Homeostasis All internal elements of living bodies are ordered, interconnected, and interdependent, which leads to a qualitatively new result—the emergence of autonomy, integrity, and constancy of the internal environment (homeostasis). Homeostasis is the state of dynamic constancy of the internal environment, which manifests itself in the stability of the chemical composition, physical and biological properties, metabolism, and physiological and many other parameters. The state of homeostasis ensures the relative independence of organisms from the external environment, as well as a relatively constant level of activity in the given organism, despite fluctuations in environmental conditions. Cells are isolated complex systems consisting of many subsystems, blocks, complexes, and molecules. All elements of the system are interdependent and interconnected. Such a system is a complex monolithic unity. Thus, orderliness, organization, and interconnection of the discrete elements of the cellular system also give rise to their integrity. The cells as a whole react to various stimuli, move, and multiply, and they have a standard set of biochemical reactions and various functions in common. Cell homeostasis is characterized by the constancy of volume, shape, features of differentiation, specificity of metabolism and functions, and much more. The integrity of living systems is determined by a strict hierarchy of construction, integration, and coordination of all components via genetic regulation, as well as intercellular communication. Thus, cells are built and function as autonomous, integral, stable bodies through the integration of all molecules, organelles, and compartments into a single whole. Multicellular organisms, such as mammals, are also a heterogeneous entity. This unified system of cells, tissues, and organs is regulated by the genome, but it is also coordinated by the neuroendocrine and immune systems. Homeostasis of such

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complex bodies is characterized not only by the internal homeostasis of cells, but also by the constancy of their qualitative and quantitative composition, the presence of special tissues and organs, the presence of systems for their regulation and communication, and the stability of their metabolism and various functions. The homeostasis of any given organism is specific, associated with the evolutionary level of development of the relevant species and genetically determined. For example, the human body has hundreds of different specific homeostatic indicators that characterize the state of cells, tissues, systems, and the organism as a whole. In particular, it is a constant concentration of water and ions inside cells, ratio of cellular blood components, body temperature, intensity of oxidative phosphorylation, heart rate, etc. At the molecular level, the number of chromosomes remains constant, the genes remain unchanged, and the genetic code and nucleic acid molecules are stable—genetic homeostasis is maintained. The metabolism is strictly controlled in cells through the synthesis of certain enzymes, the optimal number of ribosomes, a strictly defined structure of molecules, etc. At the level of the body, biochemical and cytological blood parameters, the pH of cells and body fluids, the respiratory rate, and the temperature are maintained constant along with hormone levels, immunological control, and many, many other indicators. Such indicators are stable and the same for all representatives of the same biological species. Ultimately, intracellular and organismic homeostasis maintain a constant and comfortable environment for the core of all life forms—the genome, which determines the key life processes involved in organizing the flows of matter, energy, and information. Homeostatic mechanisms are based on the principle of automatic control and regulation, which is typical for cybernetic systems (see Chap. 13). The control is based on closed-loop systems of regulation with negative feedback, when deviations from the initial level of the homeostatic indicator trigger the necessary reactions, which lead the system to return to the norm. Such regulation through negative feedback significantly increases the stability of the system. Thus, automatic maintenance of the constancy of the internal environment (see Chap. 12) is one of the most important properties of genomes, establishing biological autonomy and survival by ensuring the dynamic stability of their phenotypic frameworks.

5.7 Summary All cells, living beings, and their communities are highly organized open dynamic systems with unique biological, thermodynamic, and informational properties. Biological systems and living bodies consist of many components, strictly ordered in space and time, whose organized interaction determines the integrity of life. All manifestations of life are determined by the motions of numerous components. The orderliness of biological systems, which is one of the main characteristics of life, arose from the chaos of the material world in the process of self-organization, based on the physical and chemical laws of the interaction of molecules and their systems. Living

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bodies are characterized by deterministic self-organization, which is the independent construction of standard ordered structures and processes based on their own genetic information and physicochemical mechanisms. Living bodies are characterized by an incredible versatility of composition, organization, and functioning. The unity of the interacting genome and phenome in one body is one of the basic organizational principles of living bodies. All living organisms are constructed and operate extremely rationally. Successful combinations of molecules, cells, tissues, and organs, principles of organization of organisms, and biochemical and physiological processes that arose and were singled out by natural selection many millions of years ago are exploited by most modern living organisms at different levels of organization. Living bodies have biological autonomy, that is, the ability to solve independently many of the challenges of existence and survival. In particular, living bodies are able to provide themselves with metabolites and energy, support micro- and macroorganization, interact with the external environment, control their metabolism, and regularly reproduce. The strategic purpose of the lives of cells and organisms is to ensure the ability to survive and reproduce for the genome of their own species.

Part IV

The Nature of Vitality in Living Bodies

Negentropic cells and multicellular organisms are constantly impacted by the numerous forces of nature, such as mechanical influences, thermal motion of molecules, radiation, various fields, chemically active substances, osmosis, and others. They are often stronger than the physical and chemical forces that stabilize the structure, order, and organization of living bodies. Therefore, sooner or later, the forces of nature inevitably cause the process of dissipation of cells and their derivatives. Vitality (the vital force) is a set of biological mechanisms, processes, and functions directed against the internal and external forces of dissipation acting on living bodies. Life can only be sustained if cells and organisms constantly counteract the steady growth of entropy. The “vital force” is underpinned by constantly proceeding biochemical, biophysical, and cytological vector processes, which are controlled by the genome and aim to restore structures and organization destroyed by dissipation. These processes temporarily balance and compensate for the disturbing forces of nature, thereby ensuring survival, but also perform work, condition functions, and ensure the renewal of living bodies. The vitality of organisms is based on the set of properties, functions, and processes described below.

Chapter 6

Basic Properties and Functions

6.1 Nutrition and Digestion Living bodies consume all the substances necessary for life from the external environment. All cells and organisms need nutrients for: (1) constant renewal of their molecular composition and (2) energy. The most ancient forms of nutrition are diffusion and selective transfer of the desired organic molecules into the cell. These mechanisms arose together with the first cells that surrounded themselves with semipermeable membranes and consumed the necessary substances from the liquid environment. They are still preserved in the cells of multicellular organisms, which absorb the necessary molecules from the surrounding space constituted by the “ocean” of intercellular fluid. According to the peculiarities of absorption of carbon-containing substances, the nutrition of modern organisms can be classified as autotrophic and heterotrophic. 1. Autotrophic nutrition is the absorption and use of inorganic carbon sources to build organic matter. It is inherent in plants. Inorganic substances (CO2 and H2 O) are “eaten” by plants from the air and soil by diffusion or active processes. 2. Heterotrophic nutrition is characteristic of other living organisms. This is the absorption of organic matter from the surrounding space. The phagotrophic, or holozoic type of heterotrophic nutrition is characteristic of organisms that actively capture food into the body, where it is digested, absorbed, and assimilated. This type of nutrition is common to most animals. Osmotrophic nutrition is characteristic of fungi and bacteria, which absorb organic matter through the entire surface of the body. Some of them secrete digestive enzymes outward, breaking organic macromolecules down to amino acids, nucleotides, fatty acids, and glucose externally. These nutrients are then absorbed by the cells and digested. The following types of nutrition are distinguished according to the characteristics of energy absorption:

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1. Phototrophic nutrition is characteristic of organisms that use the energy in light to synthesize the necessary organic substances. This method is inherent in all green plants, but also in some protists and bacteria. 2. Chemotrophic nutrition is characteristic of organisms that use the chemical energy of nutrients to synthesize ATP, which can be used to synthesize organic substances and perform of work. This is typical for all animals and fungi, and also for most unicellular organisms. It should be noted that the cells of some organisms have metabolic flexibility. For example, in plants, cells of green leaves behave like photoautotrophs in the light and like chemoheterotrophs in the dark. The mechanisms of feeding arose and developed in the process of evolution. Initially, the only processes were selective diffusion. Later, some protozoa began to perform taxis, which is an active movement towards the source of “tasty” molecules in order to actively absorb them. Then the mechanism of endocytosis emerged. This is the absorption of relatively large molecules, their aggregates, and the debris of dead cells. After that, certain large unicellular organisms developed mechanisms for the absorption of entire smaller protozoa, which gave rise to the phenomenon of predation. Somewhat later, with the emergence of colonies of protozoa and simple multicellular organisms, the phenomena of parasitism and commensalism appeared. Digestion is the process of breaking down foreign organic macromolecules to their non-specific constituent monomers for further absorption and use in order to build their own specific organic substances and macromolecules. Digestion performs three important functions: (1) it forms a supply of small organic molecules for building a cell’s own macromolecules; (2) it destroys foreign macromolecules that cannot be used by the body; (3) it prevents the penetration of pathogens and toxic substances into the body. In mammals, food is broken down to simple substances that are not speciesspecific in the stomach, and then in the intestine, by special enzymes. Proteins are broken down to amino acids, polysaccharides to monosaccharides, and nucleic acids to nucleotides. Such monomers are identical in all living beings. These molecules are used to synthesize, for example, proteins, which are essential for of a given organism or species. Digestion is characteristic of both unicellular organisms and individual cells of multicellular organisms. This is the so-called intracellular digestion, used by cells to digest captured aggregates of lipids, proteins, and carbohydrates using specialized lysosomal enzymes or cytoplasmic hydrolases. Similarly, their own worn out macromolecules are destroyed and then digested, and new ones are immediately synthesized in their place. The cellular immunity of organisms is also based on this principle. Here, genetically foreign material or bacteria are absorbed and then digested by phagocytes. In one way or another, all living organisms on Earth are connected with each other by nutritional processes. If we consider the biosphere as a whole, it is obvious that autotrophic and heterotrophic organisms nourish each other mutually (syntrophy). In particular, plants form organic matter and oxygen from the CO2 and H2 O of the

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external environment, and heterotrophs use this oxygen and organic matter, returning carbon dioxide and water to the environment. The circulation of substances is closely related to the circulation of energy. Thus, the nutritional process is of capital importance, since it supplies an organism with the matter and energy needed to maintain high orderliness and to ensure the metabolism and various functions aimed at survival.

6.2 Water Consumption As noted earlier (Sect. 1.7), water is one of the main substrates for life. Cells and organisms contain approximately 70% of liquid water, which is essential for their normal functioning. A decrease in the concentration of H2 O by 20–30% leads to significant deterioration in the work of living bodies, and a further drop can completely terminate the functional activity or even lead to death. Therefore, cells and organisms invariably maintain aqueous homeostasis. For the same reason, the freezing of biological entities is dangerous to life, not due to extremely low temperatures, but primarily because of the transformation of liquid water (“living” water) into solid ice (“dead” water). Cytoplasmic membranes are virtually impermeable to water, which contributes to its retention by the cell. Intracellular water is constantly used for the multitude of physicochemical and biological processes in the cell. It is used for dissolving substances and hydrolysis of salts, biopolymers, and ATP, and also for photosynthesis in plants. A lot of water is used by the cell as a source of protons and electrons (during its dissociation) in biochemical or biophysical processes. Part of the water still leaks out of the cells, especially if the external environment is hypertonic. In addition, water is ejected from the cell during the removal of dissolved toxins into the external environment. There is no “reserve” water in the cell, since all water is “bound” with molecules and structures, or participates in processes and provides internal mobility. Therefore, in order for the cell to survive, water must constantly be allowed to enter in order to maintain not only aqueous, but also general structural and functional homeostasis. Although a small amount of water is formed during certain biochemical reactions, it is not sufficient to replenish the constant losses. Cells possess special mechanisms for the intake of water from the external environment: 1. Osmotic mechanism (Fig. 6.1). Osmosis is a unidirectional diffusion of water molecules through a semipermeable membrane as a solvent. Osmosis is caused by the difference in the concentration of solutions on either side of the semipermeable membrane. 2. Colloidal-chemical mechanism (swelling). This mechanism is inherent in plant cells and is due to the absorption of water by protoplasmic biocolloids and structural elements of the cell membrane.

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Fig. 6.1 Scheme of water entry through the membrane by diffusion (1) and through a water channel formed by aquaporin (2)

3. Electro-osmotic mechanism. Electro-osmosis is the movement of water dipoles caused by the electrical potential arising on the membrane. The potential difference across the membrane is determined by selective permeability, which results in an asymmetric distribution of ions on either side. 4. The mechanism of water inflow from the external environment through a water channel formed by aquaporin (Fig. 6.1). Aquaporins are special proteins that form water channels, or pores, by embedding themselves in the lipid bilayer of membranes. The transport activity of aquaporins is regulated by their phosphorylation and dephosphorylation. Multicellular bodies also have a range of anatomical, physiological, and molecular mechanisms for water uptake by organisms. For example, most terrestrial plants obtain water through osmosis using a special underground root system. Mammals obtain water in three main ways: through drinking, with liquid food, and also through metabolism.

6.3 Respiration The overwhelming majority of living bodies absorb oxygen from the surrounding space. Oxygen is necessary for the final oxidation of organic substances and the extraction of energy for the formation of ATP, which in turn provides energy for metabolic processes and various functions. External respiration, or gas exchange, is the absorption of oxygen from the surroundings and the release of carbon dioxide into the external environment. In mammals, external, pulmonary respiration is controlled by the respiratory center of the central nervous system; intercostal muscles and the diaphragm are involved in the act of respiration. They provide inhalation and exhalation by repeated contraction

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and relaxation. Gas exchange is carried out in the lungs by the diffusion of gases through cell membranes of the epithelium of mucous membranes. Selective absorption of O2 from the air by the blood occurs through the cells of the epithelial tissue lining the inner surface of the alveoli. Hemoglobin of red blood cells binds O2 and transports it through the vessels and capillary network to all parts of the body. Oxygen penetrates by diffusion into the cells of all tissues and organs. Cellular respiration takes place in the mitochondria, where the process of oxidation of organic substances and the transformation of energy into chemical bonds of ATP are completed (see Sect. 7.2.2). Organic molecules are sequentially cleaved and protons and electrons are gradually subtracted from them in a chain of enzymatic reactions. Eventually, at the end of the mitochondrial respiratory chain, they combine with oxygen to form water. It is the energy of moving elementary particles that is used to generate and store energy in ATP. Many aquatic organisms, such as fish, use their gills to extract dissolved oxygen from the aquatic environment. The rest of the process for using oxygen is the same as in terrestrial animals. Insects have special tracheas, tracheoles, and respiratory sacs through which gas exchange takes place. Many organisms absorb oxygen from the environment by diffusion through the body’s surface cells. For example, plants, fungi, and unicellular organisms also breathe oxygen from the environment, and this is then diffused into actively functioning cells. Cells of all of these organisms have mitochondria, which use oxygen for the final oxidation of organic matter up to water, converting energy and storing it in the form of ATP. However, certain primitive unicellular creatures, such as anaerobic bacteria and yeast, can do without oxygen. Some parasitic worms that live in the anoxic environment of the digestive tract of animals can also do without oxygen. They obtain energy through chemosynthesis, fermentation, or glycolysis. Thus, the processes of external and cellular respiration are evolutionarily very ancient and are characteristic of almost all living organisms. They condition the energetic, and hence all physiological and metabolic capabilities of organisms. This determined the emergence of a variety of functions, the complexity of organization, adaptation, and progressive evolution.

6.4 Excretion Numerous products are formed during the processes of metabolic chemical reactions in animals, many of which cannot be used by a cell or an organism. Some substances are toxic at certain concentrations. Many such substances are destroyed or neutralized in cells. Yet, some metabolites cannot be broken down due to a lack of the necessary conditions. Such substances are actively eliminated from the body. For example, the disintegration of amino acids as a result of protein metabolism leads to the production of ammonia. As ammonia is rather toxic, it is converted into urea by enzymes in the

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liver cells, and this is then released into the bloodstream, filtered by the kidneys into the urine, and excreted from the body. Excretion is inextricably linked with water exchange, since the vast majority of unnecessary substances are released in dissolved form. Large amounts of carbon dioxide are formed in cells in the process of catabolism, as the end product of the destruction of organic substances. In high concentrations, it can lead to acidification of the internal environment of cells and the body, which disrupts the work of enzymes and the functioning of organs. Therefore, it is constantly evacuated from cells into the blood and from there released through the lungs into the external environment. An organism also expels foreign and unnecessary substances that come from food or water. For example, the breakdown products of food and undigested substances are excreted through the intestine, and excess sodium and potassium salts are excreted through the kidneys and the skin. Very similar metabolic processes take place in the cells of plants, fungi, and protozoa. They also emit carbon dioxide as the end product of metabolism. Plants, in addition to this, release oxygen as a by-product of photosynthesis, providing a substance necessary for the vast majority of the world’s inhabitants. The processes of excretion are energy dependent and are associated with the consumption of a fairly significant amount of ATP. However, this is justified, since the processes of excretion contribute to removal of useless unorganized matter from living bodies. This reduces the entropy of living systems, supporting the maintenance of high orderliness. Any selectively permeable surface that connects the interior to the external environment may serve as a site of excretion, including for example the cytoplasmic membrane of unicellular organisms, the epidermis of lower invertebrates, the trachea of arthropods, the gills and skin of fish, and the lungs and skin of mammals. Highly organized animals have dedicated excretory organs that discharge waste into the environment through special ducts and pores. Metabolic waste is delivered to them from all over the body through the circulatory system. They are then absorbed and excreted from the organism. The main excretory organs in mammals are the intestine, skin, lungs, liver, and kidneys. Excretion processes also perform a number of important homeostatic functions: 1. Removal of molecules that are by-products of metabolic chains. This is very important, as it is necessary to maintain the direction of biochemical reactions, many of which are reversible and require constant removal of products. 2. Regulation of the ionic composition of fluids in cells and organisms. It is known that a change in the concentrations of H+ , Na+ , K+ , Cl− , Ca++ , and other ions leads to instabilities in metabolic and physiological processes. 3. Regulation of the water content in cells, tissues, and body fluids. This maintains the necessary conditions for the work of enzymes, the course of biochemical and physiological processes, and osmoregulation. Thus, the processes of excretion constitute a very important part of the metabolism, providing an optimal composition of the internal environment, which creates normal conditions for the functioning and survival of living bodies.

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6.5 Motion Molecular and atomic motion. Each molecule in a biosystem carries out several types of thermal motion, in particular, reciprocating, rotational, oscillatory, as well as individual fluctuations. These motions are very fast, so molecules can experience millions of conformations and collisions per second. All these types of motion lead to the successful convergence of the corresponding parts of the cells and the interaction of molecules. Thus, thermal motion is the basis of life, as it ensures diffusion, contact, and interaction of molecules in cells, as well as all biochemical and biophysical processes. All physicochemical reactions are a combination of dynamic molecular and atomic processes provided by various types of motion. In particular, when the substrate enters the active site of the enzyme molecule as a result of diffusion, it causes the movement of its polypeptide chains, which changes its conformation. The substrate molecules move and orient themselves in a certain way in the active site of the enzyme. The atoms of the functional groups of the active site of the enzyme interact with the substrates, breaking some chemical bonds and forming others, as well as forming new products. In this case, protons, electrons, methyl-, acetyl-, hydroxyl-, and other functional groups move from one molecule to another. The enzyme then changes its structure again due to the movement of the polypeptide chains, the active site opens, and the resulting reaction products are released into the external space. After that, the enzyme once again acquires its original conformation. Such processes are repeated many times at an extremely high rate, reaching many thousands of transformations per second. All of these are examples of molecular and intramolecular types of motion that provide for a variety of vital processes, from metabolism to physiological processes and the behavioral reactions of the whole organism. Motion of cellular components. All components of the nucleus and cytoplasm are in constant motion. This makes sure that the necessary structures and molecules are in the right place at the right time, thus guaranteeing the flow of hundreds of genetic processes and thousands of biochemical processes contributing to the cell’s metabolism. The colloidal content of the various parts of the cell can switch from a liquid sol to a solid gel state and vice versa, which also regulates the rate of motion of cytoplasmic molecules and organelles. Vesicles and organelles can move through the cytoplasm using special mobile proteins and cytoskeleton fibrils. The cytoskeleton can change the shape of a cell, participate in the formation of outgrowths of the cytoplasmic membrane, move chromosomes, and so on. Thus, cells have a strictly ordered colloidal structure, but at the same time remain extremely dynamic. Enzymes of certain biochemical processes, structural and functional complexes, and organelles are flexibly fixed at certain locations, whereas water molecules, metabolites, substrates, and all other kinds of components move continuously among them at extremely high rates. Migration of individual cells and cell populations. Cell motion is very important in the early stages of embryogenesis. Individual cells of different parts of the embryo

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can migrate to other regions (over a fairly considerable distance) and form a specific population, from which a given organ is then developed. For example, cells of the neural crests of the neurula of an early embryo are capable of extensive, regular migrations throughout the embryo. Some of them are included in the epidermis or skin, while others move inward and form spinal ganglia, nerve nodes, etc. The process of differentiation of migrating cells is controlled by their cellular microenvironment. During embryogenesis, cells do not move chaotically, but in a strictly ordered manner. They recognize each other precisely and thus form layers or groups with certain properties. For example, germ layers are formed in this manner during gastrulation, possessing specific structure and spatial arrangement. The reason why cells migrate in a certain direction is chemotaxis. In addition, cells seem to sense the microstructure of their environment and move along certain structures. The processes of cell recognition and adhesion determine them to a certain structural and functional reorganization, direct their movement, and halt them at a certain location. Embryonic mesenchymal cells migrate singly or in small groups. They move by means of amoeboid movements. Epithelial cells (single-layer groups of cells in close contact with each other) usually move as a whole layer. Motion at the level of body parts and organism. Many living organisms are capable of moving as a single body. Many organisms contain free-living cells that do not have constant localization and are capable of passive or active movement. For example, erythrocytes, platelets, and leukocytes move passively with the blood flow. Some leukocytes and neuroglial cells are capable of active independent movement. They are able to form pseudopodia and perform amoeboid movements. Therefore, they can “crawl” out of blood vessels, “crawl” into tissues, and move towards foreign bodies to neutralize them. The ability of sperm to move in a liquid medium enables the processes of insemination and fertilization, and hence the very phenomenon of reproduction. Cells living freely in nature, such as unicellular cells and bacteria, are able to move actively by means of special mechanisms. Examples are: (a) using pseudopodia (amoeba); (b) using flagella (euglena green, lamblia); (c) using special outgrowths of the cytoplasm—undulating membranes (trypanosomes, leishmania); (d) using cilia (ciliate shoe), etc. Animals are characterized by their ability to move. They can move in any direction as a solid physical body, despite the complexity of their internal and external structure. With the help of contracting muscles, they can move selectively and use their body parts purposefully, changing their position in space, performing work, and turning and moving in any direction. This ensures their ability to obtain food independently, avoid unfavorable factors and predators, seek a sexual partner, and reproduce. In addition, blood and lymph circulation, and massive transfer of water, various substances, and gases is carried out inside the organisms of many animals. Thus, orderly movement at all levels of organization stands among the main conditions for the course of life’s processes of existence and the survival of cells and organisms. That is, the many types of movement discussed above form the basis for the constant activity of living bodies and the continuous work they do to counter unfavorable factors, as well as to ensure reproduction and distribution.

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6.6 Reproduction Reproduction is a strategic mechanism of survival for the genome, but not for living bodies themselves. This phenomenon will be discussed separately and in detail in Chap. 9.

6.7 Summary Living bodies possess a genetically determined set of properties which provide for a variety of functions and means contributing to their survival. Nutrition underlies the metabolism and the maintenance of homeostasis. Survival is only possible if water is consumed constantly and supplied to the cell for maintenance of aqueous homeostasis, and also general structural and functional homeostasis. Breathing provides energy, and therefore maintains all the structural, metabolic, and physiological capabilities of cells and organisms. Excretion is a highly important part of the metabolism, necessary to ensure the constancy of the internal environment. Orderly motion at all levels of organization is one of the main conditions for the flow of life processes, and also the existence and survival of cells and organisms. Motion is life and life is motion. It should be noted that the basic functions and properties are integral and inseparable from each other, as they provide for the metabolism, structure, and functional activity of organisms. They promote the viability and prolonged stable existence of living bodies in the external environment. Living organisms have a set of properties that distinguish them from inanimate bodies. It is not possible to single out just one property that determines the living. It is the complex of all these properties that determines a qualitatively new state of matter.

Chapter 7

Basic Processes and Mechanisms

7.1 Bodies, Processes, Mechanisms, Interactions, States, and Functions Living bodies are physical bodies with biological features and properties. These are autonomous, highly organized biological systems, which are the units and carriers of individual life. A process is a sequential change of phenomena, events, or states of something over time, or a set of sequential actions to achieve a specific result. For example, the process of protein synthesis is associated with a series of sequential events leading to the formation of a protein: DNA transcription, RNA translation, and modification and activation of polypeptides. A mechanism is a detailed structure of the system, as well as a detailed step-bystep procedure for its operation. In this case, the activity of one or more components causes a certain animation of the rest of the system, which results in an action. For example, the presence of ribosomes, which are complex mechanisms for the targeted connection of amino acids with peptide bonds, is among the conditions for protein synthesis. The attachment of the activated methionine amino acid to the mRNA on the ribosome causes the activation of the entire polypeptide synthesis system. All processes and mechanisms in nature occur through chemical and physical interactions. Interaction is the impact of bodies or particles on each other, leading to a change in their state. A change in the state of interacting molecules, that is, a change in their physicochemical properties, leads to a modification of the quality of the biological system and a change in internal energy. Such a system acquires a new opportunity for performing special work. In the process of interactions, there is transformation of matter and energy. Nearly all interactions in cells are controlled and managed. This delivers a precise regulation of the qualitative state in any part of the cell or organism. Moreover, the states of systems can reversibly change many times, providing certain processes and functions (Fig. 7.1). Biological function is a controlled activity of certain biosystems (cells, tissues, organs) aimed at their maintenance and preservation, and the performance of all © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_7

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Fig. 7.1 Interactions of the elements of biosystems constitute the main mechanism ensuring their active existence. Regulated interactions of the constituent parts change their state. This leads to a change in the structure and properties of the system as a whole, and hence also a change in its internal energy. This can in turn be used to carry out some specific task or determine a new attribute of the system and a new level of interactions between its elements

necessary work. A function appears at a certain level of organization in living systems, on the basis of their properties and processes. It would seem that bodies and processes are completely different categories, reflecting separate properties of nature. For example, the cell body is an autonomous, stable entity, while metabolic and physiological processes (protein synthesis, glycolysis, contraction, etc.) are forms of intracellular and intercellular dynamics based on the interaction of molecules. Nevertheless, despite the significant difference in our perception of individual bodies and processes, they are essentially one and the same. They are united by common units of structure and functioning, viz., molecules. These are also autonomous, integral physical micro-bodies. In the first case, they form stable ordered systems, and in the second, mobile ordered systems. Cell structures and processes differ only in the duration and the scale of the interactions and transformations of molecules. The molecules that determine the processes (enzymes, substrates, metabolites) are extremely dynamic and subject to a fairly wide range of significant transformations. Molecules forming stationary complexes, such as proteins, membranes, and organelles are less dynamic in the sense that they are subject to transformations at a lower rate and only within the limits of existence of these systems. Thus, all cell structure is also a result of the interaction of molecules. This is a process of existence of the systems where the internal bonds between molecules are stronger than the external forces (as well as the energy of internal thermal motion).

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For example, there is a system of biological membranes consisting of a double layer of phospholipid molecules and embedded protein molecules. The hydrophobic, hydrogen, polar, and covalent forces of molecular interactions in the composition of membranes are much stronger (at physiological temperatures) than the forces caused by constant bombardment by molecules of water and substrates. Molecular processes and metabolic mechanisms constitute a set of very fast, enzyme-catalyzed reactions (rapid interactions of molecules) under the control of cells. Various complexes are also formed in the course of biochemical processes, but these complexes exist only for a very short time, of the order of microseconds. Biochemical “recognition” of interacting molecules occurs through the correspondence of their spatial structures. The main mechanism of molecular interactions is the formation or breakdown of weak chemical and physical bonds. It is difficult to say what is primary: the existence of certain physical bodies (including molecules) or processes. The difference in the scales of spatio-temporal interactions and transformations of molecules creates a false impression of fundamental differences between bodies and processes. But this is not the case. In reality, both living bodies and processes have a single molecular nature. In the organism, we distinguish stationary molecular structures, as well as molecular processes that occur at tremendous rates within the microspace of cells. Representatives of each level of molecular organization have completely different spatiotemporal characteristics of changeability. This introduces a certain complexity into our perception of the unity of bodies and processes. In addition, the same molecules can act both as units in stationary structures and as the participants in various processes. For example, higher carboxylic acids of phospholipids are included in the structure of all kinds of very stable biomembranes, but they are also one of the main substrates for the processes of biological oxidation and transformation of energy. Consequently, the same molecules in living systems are characterized by both stability in some cases and the highest rates of variability in others. The cell is also a separate integral structure. Considering it as an autonomous physical body, we note completely different rates of volatility for its constituent parts in relation to the cell itself. For example, the lifetime of a cell is generally much longer than the lifetime of macrostructural cellular elements, and the process of cell division is stretched in time by factors of millions compared to the instantaneous processes of transformation of atoms or molecules. This means that the process of changeability of a cell as a whole proceeds much more slowly and in a broader spatial framework compared with its constituent elements. The dynamism of the inner workings of the cell is manifested in many cytogenetic and physiological processes, such as mitosis, movement of organelles and cell parts, assembly and disassembly of sections of the cytoskeleton, transport of substances, and much more. But despite all this, the cell remains a separate, solid stationary body. It should be emphasized that all the macro- and microstructures of cells, and also their interaction and dynamics, come about thanks to molecular information processes controlled by the genome, and in particular, through the transcription and

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synthesis of certain structural and regulatory molecules, synthesis of the necessary enzymes, and coordinated chemical and physical interaction processes. The essence of the state of any cell is determined by its structure and internal energy. Therefore, any variations in internal energy can be accompanied by a change in the state of a given biosystem. Similar consequences can also be caused by spontaneous or forced modifications to the structure of cells, as well as changes in their qualitative or quantitative composition. Such rearrangement of structure or internal energy can occur under the influence of various factors in the external or internal environment, e.g., under the influence of various types of radiation, heat, chemically active molecules and, which is very important, under the influence of certain kinds of information. That is, a minimal information signal can lead to dramatic changes in the state and internal energy of the cell. This can lead to the performance of a specific task or function (see Fig. 7.1). A change in internal energy is accompanied by structural rearrangements within the cell. Conversely, changes in structure can be accompanied by a change in the energy. Such rearrangements determine a change in the physicochemical properties of cells, which we call a change of state. For example, the state of water in cells can be liquid, solid, liquid-crystalline, bound, and so on. The state of the cytosol in cells can also be different and possess different properties. In particular, it can be a gel or a sol, a liquid or a liquid crystal, with a phase boundary or without a phase boundary, and so on. Therefore, one and the same cell can have different properties and perform different functions in different states. In particular, it can be in a state of rest, functioning, preparing for division, dividing, etc. Thus, cells are very labile systems, involved in constant internal and external dynamics. It is the imbalance and variability of biological systems that provides the possibility of controlled transitions from one state to another. The corresponding work is performed in a different state and certain functions are accomplished. After this the system can go into a new state or return to its original one. So, on the one hand, the life of a cell is a set of specific processes that organize matter, and on the other hand, the processes themselves are a consequence of organized matter. Bodies, various structures, processes, functions, and mechanisms are closely interconnected and intertwined, and they are of the same nature. They are derivatives of interacting molecules. Speaking about the origin of life, we usually mean the appearance of living bodies, but it is more correct to talk about the interconnected origin of both bodies and processes based on the selective interaction of molecules. Moreover, given the dynamism of living systems, it is more appropriate to talk about the process of existence of cells and organisms, rather than about the existence of stationary bodies as such. Therefore, life is the entirety of structures, interactions, processes, functions, and states. Combinations of interactions, processes, states, and mechanisms can vary depending on the type of living bodies, providing the multifaceted manifestation of the phenomenon of life.

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7.2 Enzyme Catalysis The overwhelming majority of organisms exist in a rather narrow range of low temperatures, from 0 to 40 ºC. Under these conditions, the chemical bonds of organic substances are very stable and spontaneous biochemical reactions are simply impossible. Therefore, the course of all the necessary biochemical and physiological processes can be carried out only with the participation of biocatalysts, or enzymes. These are protein molecules with a specific structure, which first determine, then accelerate biochemical reactions by factors of thousands. Cells are literally loaded with enzymes. There are several thousand varieties, each of them represented in the cytoplasm by millions of copies. The qualitative and quantitative composition of enzymes in cells is controlled by differential expression of the genome, which, in turn, determines the countless varieties of cells, properties, and functions of living bodies. The molecular weights of enzymes can be from several thousand to hundreds of thousands of daltons. Enzymes are usually hundreds or thousands of times larger than the molecules they convert. All enzymes have the same fundamental principle of organization (see Fig. 7.2A). The protein globule has an active site with a special size and shape, which is the site of the process of catalytic transformation of substances, and a center of allosteric regulation which is the site of attachment of biologically active molecules. Among the myriad of possible biochemical reactions in cells, enzymes selectively catalyze only strictly defined reactions, and convert only specific substances (substrates) along a biologically beneficial path and only into the desired products. This is the principle of enzymatic control of all metabolic and physiological processes. Enzymes are molecular tools that selectively capture certain molecules out of millions of possible ones, process them quickly and accurately, and then release only the necessary finished products. The main feature of the mechanism of enzyme catalysis is the formation of unstable intermediate compounds, known as enzyme–substrate complexes, which almost instantly decompose into a free enzyme and a reaction product (see Fig. 7.2B). Alternatively, the two substrates and an enzyme form an unstable activated complex which immediately breaks down into a free enzyme and a more complex product. That is, the reaction can go in one direction or the other, depending on the environmental conditions. Enzymes work like automatic machines, performing thousands of standard transformations of substances and energy every second. Likewise, enzymes do not violate, and even exploit the laws of thermodynamics and chemistry for their own purposes and in the interests of the cell. Biochemical reactions could not be carried out in the absence of enzymes, or would proceed chaotically and too slowly, which would not allow supporting purposeful life processes. In addition, enzymes determine the generation and targeted use of energy, for example, for the transfer of molecules across membranes, for muscle contraction, for the synthesis and change of conformation of macromolecules, etc.

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Fig. 7.2 The organization and functioning of enzymes. A—organization scheme. The main functional parts of enzymes: active site—attaches the substrate; allosteric site—attaches regulatory molecules. B—mechanism of action of enzyme E. Stages of enzyme catalysis: 1—convergence and orientation of the substrate S in the active site E + S; 2—formation of the enzyme–substrate complex ES; 3—formation of an unstable enzyme–product complex EP; 4—release of reaction products E +P

Some enzymes have very complex structure and resemble intricate engineering microconstructions. This is exemplified by ATP synthase, which is a very sophisticated protein complex, consisting of a dozen different subunits, and gracefully integrated into the inner mitochondrial membrane. This complex enzyme converts the energy of an electrochemical gradient, by the process of proton transfer across the membrane, into the energy of chemical bonds of ATP (see Fig. 7.3). Enzymes can be conjugate if they catalyze two or more biochemical reactions connected in such a way that the total change in the sum of their free energies ensures that the process proceeds in a favorable direction from the thermodynamic standpoint. In this case, enzymes combine thermodynamically favorable processes with energetically unfavorable reactions. This is how constructive anabolic processes become possible. This principle of conjugation of biochemical reactions underlies cellular metabolism and is the basis for the existence of living bodies. Depending on the type of reaction catalyzed, tens of thousands of different enzymes are conventionally classified into six different classes:

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Fig. 7.3 Enzymes are molecular machines, and constitute the main instruments and mechanisms of living systems. Structure of one of the most complex and important enzymes, ATP synthase, which continuously synthesizes ATP. Proton-translocating ATP synthase consists of two parts: a proton channel (F 0 ) integrated into the membrane, consisting of 13 subunits and a catalytic subunit (F 1 ) immersed in the mitochondrial matrix. The “head” of the catalytic site is formed by three α- and three β-subunits, with three active sites in-between. The energy of moving protons allows the synthesis of ATP. The catalytic cycle is subdivided into three phases, taking place one after the other in three active sites. First, ADP and P substrates are attracted to the active site, then a bond forms between these substrates, and this is followed by release of the end product of the reaction in the form of ATP. With each transfer of three protons through the F 0 protein channel from the intermembrane space, all three active sites catalyze the next stage of the reaction. All parts of this extremely complex nanotechnological device work in concert, incredibly fast, continuously, and with mathematical precision

1. Oxidoreductases catalyze redox reactions. They carry protons, electrons, and oxygen. 2. Transferases accelerate the transfer of functional groups of atoms from one substance to another. 3. Hydrolases catalyze hydrolysis reactions, breaking various bonds with the participation of H2 O. 4. Lyases catalyze the addition of groups at double bonds or the removal of groups due to the breaking of double bonds. 5. Isomerases accelerate isomerization reactions, bringing about intramolecular transfer of groups with generation of isomeric forms. 6. Ligases provide for synthesis of organic substances from two initial molecules using the energy of ATP. Each class has hundreds of varieties, depending on the nature of the substrates involved and the relevant chemical bonds.

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A kind of “division of labor” is observed among these molecular “machines”. Thousands of enzymes in every cell catalyze their own, strictly specific reactions. Moreover, diverse types of cells have features dictated by their enzymatic composition, which determines the specificity of their functioning. Different enzymes are localized in different parts of a cell, ensuring the independent course of many different biochemical processes. Specific enzymes are concentrated in different organelles, which means that only their inherent reactions will take place in those organelles. Complexes of enzymes that catalyze a sequence of transformation reactions of some initial substance form polyenzyme conveyors or metabolic chains. For example, there is a set of ten glycolysis enzymes, jointly localized in certain sites of the cytosol, and a set of eight enzymes of the citric acid cycle, localized in the mitochondrial matrix. The product of the first enzyme becomes the substrate of the second, and so on. In this way, complex biochemical processes are significantly accelerated, substrates are not wasted, time is saved for the delivery of the necessary molecules, and the biochemical processes are directed strictly along certain paths of transformation, without producing unnecessary products. That is, the flow of matter and energy is directed strictly along certain “paths” which are “paved” in an orderly way with the relevant enzyme globules (see Fig. 7.4). Features of the metabolism of different cells result from their particular enzymatic composition. In turn, variations in the enzyme composition are due to the differential expression of the genome. Thus, the genome plays a decisive role in this case as well. The rate of the general flow of matter along the metabolic pathway is constant and controlled by the key enzymes. One or two key enzymes, operated by the genome, regulate the intensity of product formation in the chain of biochemical reactions. Such enzymes are usually controlled by the genome through the metabolic pathways of a cell or an organism. Other groups of enzymes are regulated with the principle of negative feedback by the amount of the product. That is, low concentrations stimulate the enzyme, and high concentrations inhibit it. This enables an accurate regulation of the rate, the quantity, and the direction of chemical processes, as well as the magnitude of the flow of matter and energy in the cells. Many enzymes are complex proteins, consisting of a protein globule and a nonprotein part—a coenzyme. It is the coenzyme that provides the contact between the protein and the substrate, “loosens” its chemical bonds, and makes the substrate reactive. Many vitamins and metal atoms can serve as coenzymes. Usually, coenzymes are located in the active site of an enzyme, which is a small part of the protein molecule where the substrates are fixed and converted into reaction products. Biochemical reactions are made possible and their rate increased due to an increase in the probability of interaction of molecules, their precise orientation in the active site, and a reduction of the activation energy barrier. The energy barrier is lowered thanks to (a) maximum convergence of the substrates, (b) action of the atoms of the active site on certain atoms of the substrate, and (c) changes in the energy of the electrons.

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Fig. 7.4 A plan of the basic pathways of cell metabolism looks similar to the electronic circuits of computers. A—Classic diagram of structural and functional blocks and pathways of cell metabolism. Each dot represents a specific chemical reaction and its enzyme. The diagram shows the main pathways for the transformation of substances and energy, which are, as it were, “cobbled” with enzymes. The main advantage of enzymes is their ability to select only the necessary interactions from the myriads of possibilities, and increase the probability of such unlikely processes by many orders of magnitude. The aggregate of thousands of enzymes in a cell forms a global structural– functional matrix of selective catalysis and selective transformation of substances and energy. B—A diagram of the structural and functional system in an electronic device, representing a matrix of selective pathways for conducting matter, energy, and information. Similarly to the cellular matrix, it consists of structural and functional blocks connected by communication channels. Each element of the matrix performs its own specific task. The interconnected work of thousands of elements enables the device to perform absolutely prodigious processing feats. This is approximately how we imagine the nanocybernetic colloidal matrix of cell protoplasm. What we have is a standard extremely complex cascade of material and energy interactions, whose feasibility and accuracy is provided by genetic and structural information. Each enzyme can be viewed as a kind of transistor that transforms, amplifies and directs the flow of matter and energy under the control of intracellular information

Enzymes have the following characteristics: (a) almost all enzymes are globular proteins; (b) they increase the probability and rate of reactions, but are not consumed in the process of catalysis, although they do experience reversible conformational transformations; (c) enzymes catalyze potentially possible reactions; (d) enzymes possess specificity, i.e., a particular enzyme usually catalyzes only one type of reaction; (e) a very small amount of an enzyme causes the conversion of a large number of substrate molecules, i.e., one enzyme can convert millions of substrate molecules into a product; (f) enzymes catalyze chemical processes in “mild” conditions—at normal physiological pressure, low temperature (0–40 °C), neutral acidity of the medium;

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(g) enzyme activity is regulated by the cell and depends on temperature, pressure, acidity of the medium, concentration of substrates, and concentration of products; (h) the enzymatic reaction rate is directly proportional to the amount of the enzyme (when the substrate is saturated). It is obvious that enzymes perform work. In particular, they capture substrates, fix them, change their conformation, move parts of molecules in the active site, and so on. Performing work requires energy. Some enzymes use the energy of phosphorylated substrates (for example, glucose-6-phosphate), while others use the energy of ATP (for example, ATPase). But it is likely that many enzymes are unique protein molecules that can use the energy of the thermal motion of surrounding molecules for their work, as well as the energy of thermal vibrations and fluctuations within their own molecule. Molecular systems that implement this principle of operation are called “Brownian machines”. These are micromechanical structures, parts of which move relative to each other under the influence of thermal fluctuations. Due to their structural features, only certain parts of macromolecules can actually move. Apparently, this enables the selectivity of fluctuations in certain parts of enzyme molecules, for example, only certain segments of the active site, which ensures that work is performed on the relevant substrate. Thus, enzymes can use the thermal energy of the system for rapid and targeted transformations of the necessary substances. In addition, it should be noted that, in their “social” work, enzymes follow the laws of thermodynamics. It is known that catalysts, including enzymes, are substances that help spontaneous reactions to proceed faster, providing them with an easier path, or implementing mechanisms that lower the energy barrier. Spontaneous reactions are carried out according to the laws of thermodynamics and directed towards increasing entropy, that is, towards equilibrium. Enzymes do not change the equilibrium constant of a chemical reaction in the process of work, but increase the rate at which it is achieved under given conditions. This is the main property of catalysts. All they do is to bring reactions to the same state of equilibrium more quickly than would have been achieved without them. Enzymes turn slow spontaneous reactions into fast ones, and in the end this contributes to dissipation, an increase in entropy, and a decrease in the free energy of the system. That is, the reactions of the general flow of thermodynamic destruction of biosystems are picked up and accelerated by enzymes. But in cells everything is arranged in such a way that this dissipative flow of matter and energy can at the same time also significantly accelerate and strengthen the processes that work against destruction. This is realized by conjugating enzymes and processes. When there is conjugation, thermodynamically oppositely directed reactions can be accomplished simultaneously. At the same time, the conjugating enzymes transform the potential of spontaneous reactions into the force necessary for the course of anabolic processes that consume energy, thereby maintaining the orderliness and organization of cells. Conjugation is achieved mainly through the mediation of ATP (see Fig. 7.7). It is in this way that many enzymes prevent the achievement of thermodynamic equilibrium, and hence the premature death of cells and organisms.

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Enzymes possess immense powers and perform several global functions: 1.

They enable reactions that would otherwise be improbable at the temperatures of life, increasing the probability of their implementation from fractions of a percent to a hundred percent. 2. They provide the highest possible selectivity of the flow of only those chemical reactions necessary to the cell (out of billions of possibilities). 3. They provide the highest possible rate and direction of selected biochemical processes, thereby regulating the metabolism. 4. They determine the appearance and manifestation of all functions of living bodies, including nutrition, respiration, excretion, motion, reproduction, and so on. 5. They enable the receipt and targeted economical use of substances and energy. 6. They participate in the transformation of one substance into another. 7. They participate in the transformation of one form of energy into another. 8. They are tools and mechanisms for the transformation of genetic information into its material embodiment. 9. They enable energetically unfavorable reactions of synthesis and anabolism by their conjugation with energetically favorable reactions of catabolism. 10. They are the main tools for self-regeneration and a means of counteracting entropy. These properties of enzymes provide artificial negentropic conditions in cells, which are characterized by a high probability of the occurrence of unlikely processes, selective transformation of only a limited number of universal molecules into a limited number of products, and the direction of flows of matter and energy strictly along functional paths. This creates and maintains the orderliness, homeostasis, and correct functioning of cells and organisms. Consequently, enzymes are not only accelerating factors, but also organizers, sorters, regulators, suppliers, constructors, and restorers in the unique world of cells. That is, the emergence and existence of living bodies and life as a global phenomenon on Earth became possible only on the basis of biological catalysis. Thus, selective biological catalysis is a strategic mechanism essential to implementing virtually all life processes. Some non-protein compounds can also act as biocatalysts. Certain types of RNA have the ability to catalyze the hydrolysis of phosphodiester bonds in nucleic acids. They are called ribozymes. For example, in some protozoa, splicing is carried out by the RNA transcript itself, without the participation of proteins. It is speculated that the first forms of life could have been based solely on ribozymes, while DNA, proteins, and enzymes may have emerged at a later time (see Chap. 8). Thus, it can be speculated that an ordered set of specialized protein catalysts that carry out directed transformations of matter and energy underlies all organization and functioning of cells (Fig. 7.4). There is not a single living body without enzymes, and no manifestation of life is possible without them. Enzymes are therefore molecular machines that carry out incredible processes through the mechanism of catalysis. Enzymes speed up the rate of chemical reactions tens of thousands of times. Since the rate of chemical reactions can be accelerated two- to four-fold by a temperature

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increase of 10 °C (Van’t Hoff’s rule), it can be estimated that the acceleration of a reaction by a factor of 10,000 by heating would require temperatures above 50,000 °C! Thus, what enzymes actually do is create absolutely incredible conditions for ultrafast chemical processes at very low temperatures, close to the solidification temperature of water and very close to absolute zero. That is, living bodies are characterized by unnaturally high rates of selected reactions at ultra-low temperatures. The specificity of the work done by a given enzyme depends on its conformation, which is determined by the sequence of amino acids, specified in its turn by the sequence of nucleotides in the DNA molecules. Thus, it is the genome that controls all proteins, enzymes, structures, and functions of living bodies. Without the work of enzymes, no manifestations of life would be possible. Enzymes can be considered the “molecular robots” of cells, with the genome being their master and supervisor. It is the enzymes that build the complex architecture of cells or organisms “according to the blueprints” of the genetic programs, following the instructions of the genome. Therefore, the genome can be seen as the “legislative” basis of life, and enzymes as the “executive” basis.

7.3 Transformation of Substances and Energy One of the main differences between living organisms and inanimate objects is their highly multilevel systemic organization of matter, which can persist over long times despite the action of unfavorable factors and entropy (see Sects. 1.10, 2.3, and 2.4). However, as time goes by, spontaneous gradual destruction of the elements of the structure and organization of living systems nevertheless occurs, according to the laws of thermodynamics (see Sect. 7.4). Therefore, organisms must constantly resist disintegration. To maintain life, they must constantly consume and exploit matter and energy from the surrounding space. This enables living bodies to restore and maintain a high degree of organization over long periods. However, both substances and energy can be utilized only after transformation into the required form. Sources of substances and energy. The external environment is the source of all the substances and energy needed by cells. The main source of energy for the vast majority of living organisms is the Sun. The radiant energy of the Sun (flux of photons) is absorbed by the chlorophyll of plants, and through a series of complex molecular enzymatic processes, it is converted into a proton gradient in chloroplasts, and then, through H + -ATP synthase, into the energy of the chemical bonds of ATP (see Fig. 7.5A). This is then used to synthesize organic substances from inorganic molecules (carbon dioxide and water), in whose chemical bonds the energy of the photons of the Sun thus accumulates. A byproduct of photosynthesis (and in particular the photolysis of water) is oxygen, which is released into the environment. Energy converters. Structures such as chloroplasts and mitochondria, which are capable of converting one form of energy into another, are called energy converters. They are like generators in power plants, where the energy of falling water or heat

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Fig. 7.5 The main pathways and tools for the transformation of substances and energy by pairing the energy of light (A) or the energy of nutrients (B) with the electromechanical processes of ATP generation. A—transformation of light energy into the energy of chemical bonds of ATP in plant chloroplasts. The absorbed light energy is used to generate electrons and protons from the hydrogen atoms of the water molecule. The energy of these electrons moving along the chain of carrier proteins is used to transfer protons into the intermembrane space and thereby create a potential difference. Under the influence of this difference, protons rush into the chloroplast stroma through the channels of ATP synthase, and their energy is used to synthesize ATP. 1—inner membrane of thylakoids, 2—electron and proton transport system, 3—ATP synthase. B—transformation of the energy of nutrients into the energy of ATP in mitochondria. The oxidation of organic substances in glycolysis and the tricarboxylic acid cycle (TCA cycle) are a source of electrons and protons, accumulated by the molecules of reducing equivalents. Further, the energy of electrons moving along the chain of carrier proteins is used to transfer protons into the intermembrane space and create a potential difference. Protons rush into the mitochondrial matrix through ATP synthase channels, and their energy is used for the synthesis of ATP. 1—inner mitochondrial membrane, 2—mitochondrial respiratory chain, 3—ATP synthase. The similarity of the organization and tools for converting substances and energy in plant and animal cells is obvious. The only difference is in the source of protons and electrons

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energy is converted into electrical energy. Chloroplasts convert the energy of electromagnetic radiation into the energy of the electrochemical proton potential on biomembranes. This is then used to convert and store energy in the chemical bonds of ATP. Mitochondria convert the energy of the chemical bonds of various organic substances into an electrochemical proton potential on their inner membranes. The energy of this potential is used to move protons through ATP synthases (see Figs. 7.3 and 7.5) and convert kinetic energy into the energy of the chemical bonds of ATP. ATP molecules thus constitute a readily available supply of energy for most life processes. Metabolism. The transformation of substances and energy in living bodies is interconnected and is carried out in the process of metabolism—a set of thousands of different cellular biochemical reactions. There are several metabolic pathways for the transformation of energy and substances that are universal for many organisms (Fig. 7.6). In particular, glycolysis is an enzymatic pathway for converting glucose, which is a key source of energy. Glucose formed from polysaccharides undergoes gradual oxidation. Special enzymes detach hydrogen molecules one by one from the glucose molecule. The six-carbon glucose molecule in the metabolic pathway of glycolysis is first split into two three-carbon molecules of pyruvic acid (with the formation of 2 ATP molecules). Then pyruvate is converted by enzymes into 2-carbon acetyl-CoA molecules, which are further completely destroyed in the metabolic cycle of tricarboxylic acids, producing CO2 molecules, as well as H+ and e− . Once removed from acetyl-CoA and glucose, H+ and e− are bound by special coenzymes, NAD and FAD, and transferred to the mitochondrial respiratory chain. The energy of electrons moving along the chain is used to transfer the protons into the intermembrane space of mitochondria to create a powerful electrochemical potential. The energy of this gradient is used for the targeted diffusion of protons through “molecular machines” called ATP synthases. This sophisticated enzymatic complex synthesizes a significant amount of ATP using the energy of the proton electric current (see Fig. 7.5). Oxygen is used only in the final stage of the destruction of organic matter, at the end of the respiratory chain. The process of combining oxygen with the protons and electrons which were detached from organic substances is catalyzed by another intricate enzymatic complex called cytochrome oxidase. This results in the production of water, where the oxidation state of hydrogen is at its highest. Organisms possess many other ways of transforming matter and energy. But the mechanism of selective oxidation of certain organic substances with participation of specialized enzymes provides the backbone for the energy production processes in all cells. Enzymatic oxidation is a process of forced detachment of electrons and protons from various organic molecules. Together with these particles, energy is transferred into the composition of other substances, in particular, into the structure of NADH and FADH2, and then into the phosphodiester bonds of small ATP molecules. These molecules are the universal energy accumulators for all living organisms. In this way, energy is extracted, stacked up, and stored in discrete form. This is very convenient, since it enables the gradual accumulation of large reserves of energy, as well as a precisely dosed application for various types of cell activity.

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Fig. 7.6 The main stages of transformation of substances and energy in animals in the processes of catabolism. The catabolic pathway is conventionally divided into 6 stages: Stage 1—splitting macromolecules of nutrients into monomers. Stage 2—cleavage and oxidation of monomers to pyruvate and acetyl-CoA. Stage 3—complete disintegration of the hydrocarbon skeleton of acetylCoA into CO2 , H + , and e− . Stage 4—transfer of protons and electrons to mitochondria. Stage 5—the energy of movement of electrons and protons through the inner membrane is transformed by ATP synthases into the chemical energy of ATP. Stage 6—connection of oxygen with protons and electrons at the last stage of the mitochondrial respiratory chain, with the formation of water. Glycolysis, the tricarboxylic acid cycle, and the mitochondrial respiratory chain are the key metabolic processes in the transformation of substances and energy, i.e., they are the main sources of vitality. As a result, nutrients are transformed into metabolic waste products in the form of CO2 , NH 3 , and H 2 O, whereas the energy of substances is transformed into the chemical bonds of ATP

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Fig. 7.7 The ATP–ADP cycle is the main mechanism for coupling incoming energy and cell activity. This “simple” mechanism, implemented by special enzymes, is typical for almost all living things. This is a biochemical mechanism of conjugation of endothermic and exothermic reactions, i.e., destruction with creation

Thus, cells and organisms are self-regenerating biochemical machines that work on the basis of independently procured chemical energy and the independent synthesis of the necessary substances. For example, proteins, nucleic acids, and phospholipids are constantly resynthesized in cells, membranes are restored, ribosomes are formed, etc. The totality of the thousands of different chemical reactions of metabolism is precisely regulated and coordinated in space and time. The rate, direction, and switching on and off of chemical reactions are controlled primarily by enzymes. The most general form of metabolic regulation is the control of the quantitative and qualitative composition, as well as the activity of enzymes. The quantitative and qualitative composition of enzymes is regulated by their selective synthesis. In turn, the selectivity of this synthesis is controlled by the genome. Biochemical transformations of substances and energy are closely interconnected with biophysical processes. In particular, the thermal motion of molecules is of great importance for the course of chemical reactions. It provides contacts and interactions between molecules for their further transformation. Brownian motion also enables the processes of transport and diffusion of numerous molecules into the cell, within the cell, and out of the cell. This provides the basis for generating electrochemical gradients and potentials, as well as energy transformation. The phenomenon of osmosis is of great importance for the maintenance of cell and tissue homeostasis. Many molecules and supramolecular structures of cells possess the physical properties of polarity and hydrophobicity. Cell membranes have electrical potential, and the processes in nerve cells conduct electric current. Thus, the intracellular metabolic “cauldron” of the transformation of matter and energy ensures the renewal of all components of living systems, providing all the properties and functions that underlie the life of both individual cells and multicellular organisms. The chemical energy of phosphate bonds is “released” and used by living bodies. Special enzymes with ATPase activity break down ATP in a targeted manner (where and when needed) and direct the energy to perform specific work. The amount of energy released during the hydrolysis of ATP is greater than is released during the hydrolysis of other intracellular compounds. Primarily, ATP is used to perform work aimed at maintaining the orderliness and homeostasis of the cells themselves. For this purpose, energy is supplied to the membrane mechanisms for selective transport of various molecules inside or outside

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the cells (and membrane cellular organelles). This consumes up to 30% of the energy of ATP. Even more energy, up to 50–70%, is used for processes resynthesizing the molecules needed by the cell, such as amino acids, peptides, proteins, nucleotides, RNA and DNA, fatty acids, triglycerides, phospholipids, and so on. Energy is also required to change or maintain the shape and volume of cells, and to move parts of cells or the cells themselves. The processes of cell division and differentiation are also fueled in this way, thus determining the growth and development of organs, tissues, and the body as a whole. ATP is also the main interface between exergonic and endergonic reactions (see Fig. 7.7). Cells constantly generate large amounts of the required molecules. They are capable of controlled synthesis of completely different types of substances with completely different properties. This amazing property of controlled creation is inherent only in living systems (or under conditions created artificially by humans). The microscopic volume of a cell contains dozens of metabolic conveyors for the production of amino acids, triglycerides, phospholipids, nucleotides, polysaccharides, proteins, nucleic acids, and many other complex molecules. Out of the trillions of possible variants, only a few thousand types of organic molecule are precisely and selectively generated. Moreover, metabolic pathways are organized in such a way that there are virtually no by-products or excess products. Most intermediates are immediately used in the subsequent steps of this metabolic conveyor or serve as substrates for other metabolic pathways. The majority of “dead-end” organic molecules are also used for the extraction of energy, whereupon they are oxidized to carbon dioxide and water. The amazing selectivity and specificity of biological synthesis is ensured by the presence of certain enzymes that catalyze only strictly defined biochemical reactions. Creative processes in cells are controlled by the genome through the selective expression of only those enzymes necessary for a particular process. Naturally, the destruction of used and worn-out molecules also occurs in the same vast amounts. For example, the average lifetime of cellular proteins is several hours, after which they spontaneously wear out, and are then purposefully cleaved by proteases to monomers. Hence, a unique set of organic molecules is constantly created and maintained in organisms through the transformation of matter and energy, which is essential for existence. Control over the presence and operation of enzymes, and hence over all processes of synthesis and destruction, is ensured by the genome. All physiological processes in animals, such as, muscle contraction, digestion and absorption, transport of substances and movement of blood, respiration, and so on, are also based on the biochemical and biophysical microprocesses of transformation of matter and energy. That is, whatever work is done, at whatever level of organization of life, it is always associated with the transformation of energy and matter. We can say that individual life is based on the constant massive transformation of matter and energy.

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7.4 Thermodynamic Mechanisms As already noted (see Sect. 1.10), living bodies are systems that have a molecular and cellular structural basis, and possess virtually unlimited heterogeneity and disequilibrium. They are considered to be non-equilibrium systems in which the parameters can change spontaneously or under the impact of certain forces within certain limits. If the parameters of nonequilibrium systems do not change over time, then this state of the system is said to be stationary. That is, living bodies are both stationary and non-equilibrium, capable of performing work at any time to maintain their dynamic stability. In various parts of the system, the values of the parameters can be very different. For example, there can be different concentrations of molecules in the cell. In systems where constant gradients of some parameters are maintained, various vector processes necessarily occur. For example, diffusion, osmosis, biochemical reactions, and others, are typical processes for living beings. This means that an indispensable condition for the performance of any thermodynamic system is the existence of differences at its individual points. Such a dynamic operating state of the system is maintained via the balancing processes of natural destruction (dissipation) and forced recovery due to the consumption of substances and energy from the external environment. Systems that exchange energy and matter with the external environment are called open systems. Thus, living bodies are open and non-equilibrium, but stable systems. One significant characteristic of systems is their internal energy, which consists of the sum of the kinetic and potential energy of their constituent elements. Internal energy is a function of the state of the system, and at a given point of time has a definite value. Living systems possess high internal energy, as they are highly organized structures. Transformations of energy obey the basic laws of thermodynamics: The first law of thermodynamics or the law of conservation and transformation of energy states that energy does not appear from nowhere and does not disappear anywhere; it only passes from one form to another. The transformations of energy and substances in living bodies are strictly equivalent and correspond to the law of conservation of matter and energy. The first law of thermodynamics is the general law of conservation of energy, but it does not determine the possibility of one or another transformation of energy and does not indicate its direction. The second law of thermodynamics or the law of entropy postulates that the only processes that can occur spontaneously in a certain direction are those which enable the system to passes from a less probable state to a more probable one. In this case, spontaneous processes go in the direction of increasing disorder, i.e., the entropy of isolated systems gradually and irreversibly increases. This happens because, in the processes of natural movement of matter or work, when energy is converted to another form, a certain amount of free energy of the system is always dissipated. The reverse process of decreasing entropy in a system is impossible without the use of

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additional internal energy, which is constantly replenished from the outside. That is, the transition from order to chaos in any system is spontaneous and occurs without the expenditure of energy, whereas in order to pass from chaos to order, energy has to be spent. The laws of thermodynamics are applicable to living bodies as well. They are constantly undergoing processes where energy is converted from one form to another. For example, the chemical energy of ATP hydrolysis is converted into the kinetic energy of motion of molecules through the membrane, with part of the energy also dissipated in the form of heat. And when glucose is oxidized, only 55% of the energy is stored. The rest of the energy released is spent on the uncontrolled thermal motion of molecules in the biosystem. But this part of the energy is not wasted either, since the chaotic thermal motions of cytoplasmic molecules provides energy to the processes of diffusion, osmosis, and the interaction of molecules with each other. Some enzymes use for their work the energy of the chaotic motions of surrounding molecules, as well as the energy of thermal vibrations and fluctuations within their own molecule. Enzyme molecules are micromechanical structures with constituent parts that move relative to each other under the influence of thermal fluctuations. Due to the selectivity of the motions of parts of the molecules of some enzymes, which may include only certain segments of the active site, precise work on processing substrates can be ensured by exploiting the internal heat of the system. Thus, part of the dissipated energy can be converted into work under appropriate conditions. But a significant part of the energy is still dissipated during the useful work of biological systems. This determines the direction and irreversibility of the given process. In addition, the uncontrolled thermal motion of molecules sets in motion mainly processes leading to an increase in entropy. Many molecules have very high speeds of motion and possess high kinetic energy, sufficient for uncontrolled interaction and destruction of the orderliness of biological structures. Other factors, such as radicals and radiation, for example, also lead to the destruction of elements of highly organized biosystems. That is, a transition from order to chaos gradually occurs spontaneously and without expenditure of energy. However, living organisms can avoid destruction for quite some time. It may seem that they disobey the second law of thermodynamics. This happens because, despite their autonomy, living bodies are open systems, that is, they continuously consume energy and matter from the external environment, which enables them to maintain their low level of entropy. Consumed and then transformed substances and energy are used for the continuous restoration of fluctuations and disturbances in biological systems. These recovery processes constantly maintain a high degree of organization and orderliness in living organisms. A living body can also be viewed to some extent as a contradictory biochemical system. On the one hand, the work it carries out is possible only at temperatures ranging between 0 to 40 °C, while on the other hand, that work consists in the permanent elimination of structural defects that arise continuously at these temperatures as a result of the active thermal motions of molecules. That is, on the one hand, life processes are possible only in a narrow range of rather low temperatures, while on

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the other hand, even these temperatures are quite high for living matter, contributing to the processes of its dissipation. Thus, living organisms are dissipative systems in a state of constant destruction. Only the presence of constantly ongoing anabolic processes aimed at restoration (for example, protein synthesis and DNA repair) can reduce the level of entropy, thereby allowing these biosystems a relatively stable existence. Such an internal contradiction in the existence of living systems as simultaneous destruction and restoration is one of the main qualities that distinguishes living bodies from inanimate objects. Nonbiological systems invariably increase their entropy, while biosystems always strive to maintain an ordered state. Moreover, biological systems, unlike others, are not only relatively stable nonequilibrium systems, but also have the ability to improve their structural and functional characteristics by exploiting energy and information. That is, using this consumed energy and information, they tend to evolve in such a way as to decrease the rate of production of entropy. An artificially created mechanical system does not necessarily have to perform work to maintain its structure, whereas a living organism always has to function. If for some reason an organism ceases to perform its basic functions at the temperature of its vital activity, then it irreversibly loses its structure and dies. A living system is an active, constantly working system. All metabolic processes in such a system are catalytic, and the catalysts are special proteins, viz., enzymes. The catalytic nature of the internal processes enables controlled transformation of the chemical energy of nutrition products into the required work and heat at incredibly high rates and at the relatively low temperatures of existence of biological systems. Biological systems maintain their order only thanks to anabolic processes that continuously seek to build or restore these highly organized structures, constantly subjected to thermodynamic destruction. However, if biological objects are cooled down or frozen, the processes of thermal destruction of order and metabolic processes are suspended simultaneously. Such a preserved system can come back to life when warmed up, provided that its structure has not been significantly damaged. In this way, ancient microorganisms have been revived under laboratory conditions when removed from the permafrost after tens of thousands of years “hiding” from the laws of thermodynamics. The mechanism of spontaneous destruction of living bodies and biological systems is very important for development, since it becomes clear that neither matter, nor energy, nor information has to be spent to eliminate the old and unnecessary. It is simply enough to turn off the program maintaining integrity in order for all organized systems to be spontaneously destroyed. Energy, matter, and information are used only at the creation stage. This thermodynamic mechanism is also used by nature for the global process of evolution. Billions of individuals of millions of species are constantly being spontaneously destroyed, dying naturally according to the law of entropy at no cost. However, the costly mechanism of self-reproduction of individuals ensures that species will not just disappear off the face of the Earth. And since the genomes of reproducing living bodies undergo mutations and recombinations, the restored creatures are already somewhat altered, often possessing evolutionarily

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favorable features. The fate of these bodies will also be spontaneous destruction, but with a controlled restoration of new individuals according to slightly altered genetic programs. And so on and so forth, for billions of years and generations. Organization and orderliness of living bodies is maintained via the mechanism of conjugation of energy flows in cells. That is, the energy released by destruction processes is used to ensure the occurrence of reparative events. Life is supported by many anabolic chemical reactions that cannot proceed independently outside the biological system since they would be thermodynamically impossible. These are, for example, the synthesis of proteins and nucleic acids, the formation of macromolecular complexes, and so on. However, within cells, these reactions are constantly being carried out, and at high rates. This is enabled by coupling with exothermic reactions and processes, such as electrochemical gradients, ATP hydrolysis, and so on. The resulting released energy is used by the cell to perform a variety of useful tasks. In coupled reaction processes, the main role is played by ATP, which is one of the molecules with the greatest capacity to hold energy. A significant amount of energy is released during its hydrolysis and used to carry out many anabolic reactions. Mutual transformations of ATP ↔ ADP are used by organisms as the main mechanism for conjugation of multidirectional thermodynamic flows of substances and energy (see Fig. 7.7). It is fundamentally important that it is possible to use spontaneous internal processes in living bodies to increase entropy and perform useful work. That is, the structural ordering (negentropy) and the internal energy of molecules (enthalpy) in biological systems have a certain potential to do work. Consequently, spontaneous thermal motions and destruction of order are not only a force of dissipation, but can also be a source of energy and matter for restoring and maintaining the standards of organization of living bodies, along with the use of energy and matter from the external environment. This is probably a kind of thermodynamic mechanism of life, wherein an uncontrollable flow of chaotic energy and destruction sets in motion a flow of creative and functional energy controlled by the genome (through enzymes). Consequently, the lives of living bodies are based on processes of controlled dominance of thermal chaos that arise spontaneously in biological systems at the normal temperatures of life. It is the force of spontaneous thermal destruction that constantly initiates changes in the states of the micro- and macrosystems of the cell. This determines its non-equilibrium state and continuous flows of matter and energy controlled by genetic programs, which contribute to the creation and maintenance of organization and order. As a result, it is the genome that heads the fight against the second law of thermodynamics in living nature. It is the genome that organizes structures and processes (through controlled protein synthesis) that restore the effects of dissipation. It cannot completely prevent the inevitable destruction, but it can restore itself and its phenotypic framework with great success for a certain period of time, in part by using and directing the thermal potential. Paradoxical as it may seem, it is the spontaneous processes of destruction that are the source of vitality and the basis of creation!

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7.5 Electrostatic and Electrodynamic Mechanisms The inner content of cells is a colloid. Around 70% of it is water in which various, mainly organic molecules are dissolved. Life is supported by the interactions of these molecules. Such interactions are only possible in a liquid medium, where a high rate of molecular movement is maintained. Moreover, all molecules, both organic and inorganic, are present in a dissociated state, carrying a system of electric charges on their surface. Water molecules are also dipoles, carrying both positive and negative charges. Thus, virtually all the internal content of cells consists of charged molecules. Consequently, many processes in cells and multicellular organisms are associated with electric and electromagnetic interactions, and this endows organisms with special properties. Living bodies, cells, and intercellular contents possess electrical conductivity. This is the ability of bodies or substances to conduct electric current. In particular, electrical conductivity plays a decisive role in the functions of nervous and muscle tissues. The electrical properties of living bodies are much more complex than such properties of inanimate objects, since an organism is also a heterogeneous collection of ions with variable concentrations in space and time. A feature of electrical conductivity in living systems is also the fact that substances are transferred together with electric charges. This solves many tasks of directed mass transfer in cells. For example, all polar and ionized substances are transferred from one compartment to another through a branched system of biomembranes using electrical interactions. The process of dissolution and maintenance of molecules in the dissolved state in the cytoplasm is associated with their electrical interactions with water dipoles. That is, the ionized state of cell contents endows them with an electrodynamic nature. These contents thus constitute a heterogeneous system of polarized, moving, interacting, positively or negatively charged molecules. Many biochemical reactions run on the basis of electrical interactions. For example, biocatalysis, the main mechanism of life, is based on electrical interactions in the active sites of enzymes. Such catalysis can be of an acid–base or a covalent nature. In the first case, the enzymatic activity is realized via chemical reactions of the amino acid residues of the active site that have functional groups of proton donors and/or acceptors. Their electrostatic interactions with the substrate cause the redistribution of charges, weakening of chemical bonds, and detachment and transfer of certain charged functional groups or parts of molecules. Covalent catalysis is also associated with electrostatic interactions between the substrate and charged groups of the active site. It is realized via the formation of temporary covalent bonds and enzyme–substrate complexes. All cells are covered with membranes consisting of phospholipid and protein molecules. Both have the property of amphipolarity. That is, hydrophobic parts of molecules (without charge) are located inside the membrane, and hydrophilic, charge-bearing atoms are located on the surface. As the charges of the cell surface and associated anions and cations can move, this creates a certain electric field around

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Fig. 7.8 Schematic representation of possible “electrical potentials and currents” in cells and tissues. Electrical potentials are constantly and purposefully created and changed in various sites in cells during biochemical reactions in the process of metabolism. This leads to the constant emergence of electrical disequilibrium, which causes directed ordered flows and regular interaction of charged atoms and molecules

the cells, and probably even an electromagnetic field. The cell surface is normally negatively charged, while the cytoplasm is positively charged. Since biomembranes have selective permeability, different concentrations of K+ , + Na , Ca++ , Cl− , H+ , OH− , and other ions on either side of these membranes create a membrane electric potential. The resting potential of cell membranes can reach 50–100 mV (see Fig. 7.8). The main contribution to the value of the resting potential is made by sodium, potassium, and chlorine ions. This potential is the driving force for a wide range of vital processes. For example, amino acids, glucose, urea, water, K+ , Na+ , Ca++ , Cl− , H+ , OH− , and many other molecules are transported into or out of the cells along the electrochemical gradient through special carriers. In living organisms, there is such a thing as electroexcitable tissue. These tissues are capable of reversible depolarization. They are composed of cells with membranes having a high resting electric potential. In electrically excitable cells of the nervous and muscular systems and the heart, electrical or chemical signals can lead to the emergence of a so-called action potential (110–120 mV), which is enabled by directed flows of ions through the membrane (electric current of Na+ in animals). The spread of this potential, for example, along the length of a nerve, is able to conduct an electrical impulse. Additionally, cells of the myocardium have gap junctions between them. Through these junctions, the excitation is spread at almost the speed of light throughout the organ in the form of an electric current. This results in a virtually simultaneous contraction of the whole myocardium. The perception and dissemination of information in living bodies is also based on electrical phenomena. In particular, signals from the external and internal environment are transformed by receptors into an electric current which can spread over

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considerable distances, through special cell formations, to the site where they should take effect. It is also known that work in animal brains is based on the electrical activity of billions of neurons, interconnected with each other. Electric currents circulate billions of neural signals, enabling in ways not yet entirely clear to us the phenomena of perception, recording, analysis, and use of information that comes through thousands of channels from hundreds of different receptors. Interestingly, the stimuli of all kinds are converted in receptors into specific electrical signals, which are transmitted through electrical networks to the brain for further processing. An external manifestation of electrical activity in the heart or brain is electromagnetic oscillations, which can be registered using an electrocardiograph or encephalograph. The key mechanism of life is a set of processes for transformation of matter and energy in cells (see Sect. 7.3). Here, not only chemical but also electrodynamic mechanisms come into effect. For example, the process of photosynthesis is based on the absorption of electromagnetic energy of a photon by chlorophyll (see Fig. 7.5). As a result of a number of physicochemical processes, the concentration of protons (H+ ) and electrons (e− ) in the thylakoid matrix increases, generating an electrochemical potential on the membrane. High-energy electrons are carried by special proteins along the transport chain inside the thylakoid membranes, i.e., an electric current flows. The electrons subsequently lose energy which is used by other proteins to transfer protons across the membrane into the thylakoid matrix. This leads to an even greater increase in the concentration of protons on one side of the membrane and an increase in the electrochemical potential of the membrane. The energy of this high proton gradient is used to synthesize ATP. Thylakoid membranes contain special molecular complexes, called H+ -ATP synthases. The energy of protons moving through them along the concentration gradient is converted into the energy of chemical bonds in the synthesized ATP molecules. That is, chloroplasts convert the energy of electromagnetic radiation through a number of electrodynamic and electrostatic processes into the energy of the proton potential on biomembranes, which is then further used to convert and store energy in the chemical bonds of ATP. Other energy converters—mitochondria—oxidize various organic molecules, generating a significant pool of protons and electrons. Protein–lipid complexes in the respiratory chain of the inner membranes of mitochondria contain components with different redox potentials. This contributes to the spontaneous movement of electrons along this chain, in the direction from high electrochemical potential to low. The energy of this electric current is used to transfer protons across the membrane and increase the proton gradient. The energy of this potential is then used, just as on the membranes of thylakoids, to move protons through ATP synthases and convert electrokinetic energy into the energy of ATP chemical bonds. Nucleic acid molecules also carry an electric charge which is proportional to the length of their chain. As a result of electrolytic dissociation, nucleic acids, like other acids, break down into an anion and a hydrogen ion. The hydrogen of the phosphate group dissociates in the nucleotide of DNA or RNA. That is, the nucleic acids and proteins that make up the genome are in a charged state. Therefore, the genome possesses an electric potential and possibly an electromagnetic field.

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All biochemical processes take place in a liquid medium. The acidity (pH) of the medium inside cells, as well as the intercellular media and fluids of multicellular organisms, is close to neutral, although it has some peculiarities in different biological entities. Enzymatic processes are possible only at optimum pH values. It is known that acidity is determined by the quantitative content of hydrogen ions (H+ ). Even small changes in pH (alkalosis or acidosis) can lead to disruptions in biochemical processes, metabolism, and functions. Therefore, buffer systems (bipolar charged systems) maintain the required concentration of protons in the internal media of living bodies, to maintain constant acidity. So, substances are composed of molecules, each of which is a system of charges. Cells are complex microheterogeneous systems of charged elements. Nearly all processes associated with the existence of living bodies are caused and accompanied by electrochemical and electromechanical phenomena. All particles in a cell are in electrical interaction with each other. Apparently, there is a common cellular electromagnetic field linking all electrical and chemical units into a single system. It thus becomes obvious that any disturbances in the electrical equilibrium, for example, by breaking the chemical bonds of any substance, should cause electrical and mechanical fluctuations in the surrounding molecules. This, in turn, will lead to a general change in the state of the parts making up the system, as well as a change in the system itself. Thus, electrical interactions can provide a subtle mechanism for integrating and regulating processes in the internal contents of cells and various cell systems (see Fig. 7.8). If we add to this the hypothetical electromagnetic field of the genome, this can be a mechanism whereby it can have an instant global effect on any part of the cell, as well as on any molecules and structures. The reaction and feedback of elements of the system can be just as fast. Hence, global electrical processes and interactions take place in cells, and electrical currents run along thousands of paths and in hundreds of directions. Millions of chemical reactions, which we see in external manifestations and the formation of various substances, are of an electrical nature. Any chemical transformations of substances are associated with electron and proton interactions, and displacements and relocations of electric charges. None of this is at all chaotic, but a controlled and coordinated shifting of electric charges from one molecule to another, from one organelle to another, from one part of a cell to another. This enables enormously rapid rates of communication and coordination between any parts of the cell, comparable to the speed of an electric current. The most remote and miniature parts of the cell can be almost instantly activated and made to react. Moreover, both the presence of certain currents and their direction can be controlled by the cell and the genome. Electrical processes integrate all the charged multi-heterogeneous constituents of the cell into a single system. In this way, a cell can be perceived as a kind of microelectronic physicochemical machine that does work and maintains its integrity through electric and electromagnetic interactions.

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7.6 Quantum Mechanisms A quantum is a carrier particle of the properties of matter, including physical fields. For example, a particle of an electromagnetic field is a photon, a particle of the gravitational field is a graviton, particles of atoms are protons and electrons, and so on. A quantum is the minimum amount by which a physical quantity (mass, energy, action, momentum, etc.), discrete in nature, can change. All material bodies of animate and inanimate nature are composed of atoms and molecules. An atom is a quantum mechanical particle, consisting of a positively charged nucleus and negatively charged electrons distributed over different rotational orbits. A chemical element is a certain type of atom with a specific nuclear charge. The atoms of most elements have the ability to donate or accept electrons. If an atom has unfilled outer electron orbitals, it is unstable and easily enters into chemical reactions, donating or acquiring electrons. Hence, the reactivity of elements is determined by the structural features of the outer electron shells of atoms. Combining with each other by chemical bonds, atoms form molecules of various substances. A chemical bond is a stable interaction of atoms through their electrons, which leads to the formation of the polyatomic chemical compounds we call molecules. Combinations of dozens of different atoms can form countless different molecules with specific molecular weights and various configurations. A molecule is the smallest particle of a substance that determines its physical and chemical properties. After the formation of a chemical bond, atoms lose their individuality, and the properties of molecules differ from the properties of their constituent elements. The structure and properties of molecules are determined by the spatial and energy ordering of the quantum–mechanical system formed by atoms and electrons. Chemical reactions, including biochemical ones, are the transformation of one or several substances into others that differ from the original substances in composition, structure, and properties. During the course of a reaction, there is no change in the total number of atoms and elementary particles. Consequently, chemical reactions are quantum processes associated only with the redistribution of electrons and rearrangement of nuclei, while the nuclei of atoms themselves remain unchanged. The atoms and molecules in a cell are in constant thermal motion and repeatedly collide with each other. During collisions, molecules can release sufficient energy to change chemical bonds: breaking or rearranging them, or forming new ones. In this way, molecular and quantum processes provide the basis for the formation of new compounds and new molecules. Reactions spontaneously move in the direction of decreasing the energy of substances and increasing the entropy of the system. The possibilities for reactions to occur and their rates depend on a range of conditions. The process is influenced by temperature, pressure, mechanical impacts, electric current, catalysts, and so on. Reactions can be controlled by changing these conditions. Complex compounds of variable composition, with weaker bonds between the groups of atoms (in particular, many organic substances), are the most dependent on the various factors.

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A group of reacting substances constitutes a chemical system, which can be equilibrium or nonequilibrium. Equilibrium systems feature reversible reactions, and nonequilibrium systems irreversible ones, which can be chains or branched. Cells are nonequilibrium biochemical systems. It is in such systems that fluctuations, instability, and uncertainty can arise in the development of the processes. However, the direction and intensity of biochemical processes in cells is strictly regulated by selective catalysis by enzymes determined by the genome. A chemical process is a combination of sequential factors and states of a chemical system, which results in the formation of a new substance through a series of intermediate stages. This cascade of chemical transformations is based on the sequential processes of redistribution of electrons and elements. Thus, it is obvious that quantum transformations are the basis of chemical, and therefore also biochemical transformations. Almost all metabolic and physiological processes are associated with the movement of elementary particles. This includes the phenomena of photosynthesis, enzymatic catalysis, processes of oxidative phosphorylation, polarization and depolarization of membranes, and phosphorylation and dephosphorylation of macromolecules, not to mention the phenomenon of vision, conduction of nerve impulses, electrical activity of the brain, and much more. Let us now consider some specific examples of quantum biological processes. The main source of energy for life on Earth is the Sun. The main process converting the energy of the photon flux into the energy of chemical bonds of ATP, and then into the chemical bonds of organic substances is photosynthesis. This is a typical example of the quantum processes that underlie life (see Fig. 7.5). The essence of quantum biological transformations during the light phase of photosynthesis is the absorption of light energy quanta and their transformation through a number of stages into the energy of chemical bonds in ATP. Light is absorbed by chlorophylls. These complex organic molecules are contained in special photosynthetic structures in plant cells, namely in the organelles called chloroplasts. They have complex specialized membrane structures called thylakoids, and the chlorophyll molecules, capable of capturing the photons of light, are integrated into these thylakoid membranes. Free protons, electrons, and oxygen are formed as a result of water photolysis. The concentration of protons and electrons in the thylakoid matrix increases, creating an electrochemical potential on the membrane. High-energy electrons from both types of chlorophyll are transported along the transport chain inside the thylakoid membrane by special proteins. In this way, the electrons lose energy which is used by other proteins to transfer protons across the membrane into the thylakoid matrix. This leads to an even greater increase in the proton concentration and an increase in the electrochemical membrane gradient. Thylakoid membranes contain special H+ -ATP synthases. The energy of protons moving along the concentration gradient is converted in the active site of these enzymes into the energy of chemical bonds of synthesized ATP molecules. Thus, the essence of the light phase in the process of

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photosynthesis is the dynamics and sequential transformations of elementary particles—photons, protons, and electrons, that is, quantum–mechanical processes that ultimately lead to the formation of high-energy ATP bonds. Likewise, the processes of oxidative phosphorylation that occur in all organisms in mitochondria have a quantum basis (Fig. 7.5). Enzymatic oxidation of organic substances with removal of the hydrogen ions (protons) and electrons takes place in the mitochondrial matrix. Electrons are transferred by enzymes to the respiratory chain of the inner membrane. There, moving from one element of the respiratory chain to another, they gradually release energy which is immediately used to transfer protons from the matrix to the intermembrane space. This creates an electrochemical proton gradient with a high potential energy. The inner membrane of mitochondria contains integral molecular complexes of ATP synthase. Passing through the membrane, the protons gradually (quantumly) give up their energy, which is also quantumly transferred into the energy of ATP chemical bonds (similar to the processes of photosynthesis described above). The phenomenon of selective enzymatic catalysis is the main mechanism for the execution of all biochemical reactions and processes, functions, and formation of structures, and therefore underlies all forms of life. The work of all the tens of thousands of different enzymes is based on quantum mechanical processes. Active sites of enzymes contain functional atoms or their groups, which have the ability to bind and orient the substrates of reactions. This occurs through the formation of different chemical bonds, and any chemical bond involves interacting electrons or interacting electrons and protons. Other functional groups of the active site act with their electrons and protons on a particular chemical bond. This causes a displacement of electrons and protons, a change in the conformation of the substrates, and a weakening of the bond, eventually leading to its rupture and resulting in other orientations of the electron shells. The central matrix processes, such as replication, transcription, translation, and repair, are also complex enzymatic processes with a quantum basis. However, the possibility of quantum interactions of molecules and cells at a distance via various fields and radiation (“wireless” transmission of energy and information) remains unproven. Hence, nonspecific quantum mechanisms of interaction, characteristic of all matter in the Universe, are the basis for the formation of all biological structures and the general course of all life processes. The peculiarity of these processes in living organisms comes from the creation and maintenance of specific conditions (based on genetic information) for the flow of quantum processes only in certain places, at a certain time, with certain molecules, and in a certain direction. That is, the quantum mechanism is the main mechanism used by living systems, but only as the basis for creating a genome-programmed ordering of structures and processes in cells.

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7.7 Informational-Genetic Processes and Mechanisms Life has an informational backbone, which is discussed in detail in Sect. 1.12. A description of the main informational-genetic processes and mechanisms will be presented in Chap. 12. Therefore, in this section, we will only briefly dwell on genetic mechanisms, mainly from the point of view of their direction and purpose. These are microprocesses, imperceptibly proceeding in the genome, but they have tremendous consequences, both for the individual life of the organism and for the planetary phenomenon of life as a whole. 1. Processes involved in reconstructing genomes and living bodies (described in detail in Chap. 9) Reproduction of its own kind is one of the main properties of a living body. Replication is the central molecular mechanism of reproduction for all the vast variety of living organisms and cells. Reproduction of all kinds of living beings is based on the mechanism of DNA doubling and splitting. This complex multistage process of duplication of DNA molecules in the genome occurs in the nuclei of cells in preparation for their division. Dozens of different enzymes are involved in this process, most of which are standard for all living organisms. Every double helix DNA of all the chromosomes of the karyotype unravels to form two separate strands of polynucleotides. Each of these strands acts as a template for the precise synthesis of its complementary strand, resulting in the formation of two equivalent DNA molecules. Doubling of the genetic material in the genome is the basis for cell division. Replication is followed by a process of evenly dividing and distributing genetic material in daughter cells. This is a complex process with several stages that results in the appearance of two equivalent genomes of daughter cells instead of one maternal genome. Thus, the mechanism of directed transformations of genetic material and genetic information determines its continuity and the continuity of its material carriers—the genomes of living bodies. 2. Informational-genetic processes involved in developing and maintaining the metabolism and integrity of living bodies (for more details, see Chap. 10) After fertilization, the development of multicellular organisms begins. It is based on several key processes: (a) massive consumption of substances and energy from the external environment, (b) transformation of substances and energy into the desired forms, and (c) construction of cell structures, (d) intensive cell division, (e) cell differentiation, and (f) organization of tissues, organs, and parts of the body. All of these processes are controlled by the genome and supported by the work of special structures and enzyme proteins. The formation of certain proteins at different stages of development is ensured by differential gene expression. That is, at each stage of development, in different cells, in different tissues and parts of the body, special proteins, enzymes, and other molecules come under the control of the genome, which sends them along a certain path of organization and development. As a result, a fully formed complex living body appears after a certain time.

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The main condition for the further existence of living bodies is a constant exchange of substances and energy with the external environment, as well as maintenance of their internal metabolism (see Sects. 7.2 and 7.3). Billions of different chemical and physical transformations of molecules take place inside each cell every second. Many organic substances are purposefully destroyed for the extraction of energy. Other substances are synthesized to constantly renew the composition of cells and the body. This provides the fundamental basis for the long existence and normal functioning of living bodies. The main executors of development, maintenance of the metabolism, and homeostasis are proteins and enzymes. They are encoded by genes of the DNA in genomes, and their expression is guided by special molecular genetic processes. Here we list the main molecular genetic processes (see Chap. 14 for more details) aimed at ensuring development, metabolism, and homeostasis. Transcription is the process of formation of mediators for protein synthesis: pro-RNA on the template DNA strand. Post-transcriptional modification is the process of RNA modification (maturation). Transport refers to the removal of RNA from the nucleus to the cytoplasm. Translation is the synthesis of polypeptide chains by ribosomes. Folding is the process of modifying polypeptide chains to form proteins. Expression is the process of manifesting the properties and functions of proteins. The above informational-genetic processes are the determining mechanisms ensuring the development and existence of living organisms. 3. Processes involved in evolution Life is a process directed towards the future. Despite the mortality of representatives of any given biological species, the genome of a species continues to exist in other bodies for millions of years. Life as a phenomenon, as a process of existence and development of the planetary system of life, has existed for 4 billion years and will continue to do so. Life is evolving synchronously with the evolution of our planet and as an integral part of it. Living beings have strategic molecular-genetic mechanisms that allow the genomes of their populations and species to continuously adapt, survive, and evolve in the face of the constant variability of the surrounding world. These informational-genetic mechanisms will be discussed in detail in Chap. 12, so we will only touch upon them briefly here. Recombination is the shuffling of genetic material, for example, as a result of crossing over. Recombination of genes is also carried out during fertilization and combination of the genes of the father and mother, as well as accidental separation of chromosomes during meiosis. Mutation is an unexpected, persistent alteration in the sequence of a cell’s genetic material. This may lead to a change in the organization of the system of genes and the emergence of new traits or new variants of traits. Mutations emerge suddenly and sometimes drastically change the morphological and functional properties of the organism. If mutations occur in germ cells, they may be passed on to descendants. Hybridization is a constant shuffling of the composition and combinations of alleles of genomes as a result of free crossing within a species. Natural selection of genomes occurs on the basis of the process of natural selection

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of phenotypic traits. In this case, the most useful genes and their combinations are selected. Transgenesis is the intraspecific or interspecific transfer of genes through genetic vectors such as viruses, viroids, phages, transposons, IS elements, etc. All of the above can lead to very noticeable recombinations of genomes and significant changes in their phenotypic framework. Bioinfogenesis is the process of generating new information in the form of new alleles and genes, and fixing them in genomes during the evolution of living systems. Infobiogenesis is the process of formation of new phenotypes of living bodies under the influence of new genetic information generated in the process of evolution on the basis of mutations and transgenesis (Fig. 14.5). Thus, it is clear that these molecular informational-genetic microprocesses are simultaneous interrelated transformations of genetic material and the information contained in genomes, involved in controlling the foundations of the entire phenomenon of life, in particular, the reproduction of genomes and living bodies, the development and functioning of individuals, and the evolution of the planetary system of life.

7.8 Cytological and Cytogenetic Macroprocesses and Mechanisms Besides molecular microprocesses, cells also undergo numerous targeted cytological and cytogenetic macroprocesses associated with the interaction, transformation, and controlled movement of colossal organized cellular masses. Each individual cell, organelle, or structural and functional part of a cell can be considered as a complex engineering and technical construction, artificially built from multiple molecular elements according to the genetic projects of Nature. For example, (a) organelles are built from certain building blocks, viz., various molecules; (b) they are united into a single whole thanks to the laws of physics and chemistry; (c) in all cells of any given organism, the organelles are built according to a single plan; (d) molecules are strictly matched to each other with mathematical precision; (e) special chemical bonds and physical interactions provide for the stability, durability, and reliability of the engineered complex; (f) specific interactions of specially selected and specifically located molecules and atoms ensure the specific functions of this complex; (g) the standard functions of organelles in various cells (and even organisms) are provided by a standard set, arrangement, and interaction of molecules and atoms; (h) the functioning of such systems is characterized by cooperation, consistency, and interdependence; (i) there are no unnecessary molecules and systems; (j) there are no side metabolites, processes, and functions. Such complex microsystems of organic molecules form macrosystems of interacting organelles and cell parts. Examples are the intracellular digestion system, the protein synthesis system, the vesicular transport system, the energy transformation system, and many more. These macrosystems exist and function as a single device,

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as a single cytosystem. Moreover, they are in interconnection and interaction with each other and with all other macrostructures of cells. It is their well-coordinated interaction that ensures the life and functioning of cells as integral autonomous bodies. It is essential that all organelles are “submerged” and interact within the complex colloidal cytoplasm. Mitochondria, lysosomes, membranes, and vesicles of the endoplasmic reticulum and Golgi apparatus, ribosomes, chromosomes, and others are constantly moving in it, changing their shape and size. They change their own structural and functional state in a synchronous and interconnected way, as they exist in a single operational space. The most striking and complex example of a macroprocess is cell division associated with the ordered movement of huge cellular masses, structures, and organelles within the cell (see Fig. 9.4 and Table 9.1). Let us list the main intracellular macroprocesses during mitosis and cytokinesis. 1.

The process of formation of the most complex macroscopic systems—chromosomes form invisible chaotic chromatin filaments. This is a kind of a temporary method for preserving and storing the contents of the genome. 2. The formation of two spindle poles and the formation of a system of spindle microtubules, i.e., the generation of a completely new global protein macrostructure. 3. The disintegration of the nucleus and its envelope, release of chromosomes into the cytoplasm, disassembly of the envelope and nuclear contents, and formation of special membrane vesicles. At the same time, the huge and highly organized macrostructure of the nucleus, which occupied up to 50% of the cell volume, ceases to exist! 4. The formation of a new highly complex cell content—mixoplasm, a no less ordered or organized structure than cytosol or karyoplasm. 5. The controlled and targeted growth of spindle microtubules, involving massive protein synthesis and controlled assembly of the mitotic apparatus. 6. The precise movements and interactions of tens of chromosomes and hundreds of microtubules. 7. The organized and purposeful movement of massive chromosomes through the viscous matrix of the myxoplasm, and their precise localization and orientation in the central part of the cell. 8. The simultaneous division of the metaphase chromosome complex into chromatids. 9. The controlled movement of chromatid bodies through the dense matrix to the opposite poles of the cell. 10. The organized destruction and utilization of the mass of microtubules of the spindle apparatus. 11. The fusion of nuclear membrane vesicles and restoration of the membranes and nuclear contents around the daughter sets of chromosomes. 12. The unfolding of chromosomes and the formation of a chromatin network, leading to the reconstruction of a functionally active genome.

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13. The formation and deepening of the cleavage furrow of the body of a mother cell, with organized and targeted redistribution of macromolecular complexes and organelles to different parts of the cell. 14. The division of the body of a mother cell into 2 daughter cells. The above list clearly shows that molecular metabolic microprocesses are not the only things going on in dividing cells (these are presented in Sect. 7.3). There are also a vast amount of all kinds of macroprocesses associated with the interaction, reorganization, transformation, and movement of large-scale organized cellular masses, large cellular parts, organelles, and large macromolecular complexes (see Figs. 9.4 and 9.6). Moreover, all these complex processes are carried out by the cell in an organized manner, quickly, with great precision, and in a strict order. In multicellular organisms, such processes occur in thousands of cells and are repeated countless times, virtually without error or failure. The expediency, organization, and interconnectedness of large-scale processes serving specific purposes, such as cell division, are also striking. Among many other examples are the assembly and disassembly of the cytoskeleton, the formation and movement of membrane vesicles and organelles, the division and movement of mitochondria, the change in the shape and movement of parts of cells, and many more. Furthermore, the interactions and targeted precise transformations of large structural complexes of cells carried out while maintaining their structural and functional order. Transformations of bulky genome material and accompanying cytological macroprocesses are admirable for their complexity and accuracy, for their rationality and expediency. But the nature of the causality, the coherence and accuracy of movement, and the recognition and interaction of extremely intricate molecular complexes as a whole is still not fully understood. While we have a fairly clear understanding of specific biochemical reactions, for example, the transformation of certain molecules in the active sites of enzymes, and we have some understanding of the mechanisms and forces of metabolic processes, which are quite well explained using the laws of physics and chemistry, it is still almost impossible to understand the complexity of the regularity and repeated clarity of transformations of cellular macrostructures. The causality in the organization of their movement, interactions, and precise controllability is also unknown. However, it is clear that the material and energy basis for macroprocesses are microprocesses that provide them with substances, structures, and energy. So, along with many molecular microprocesses, such as enzymatic catalysis, synthesis of macromolecules, biological oxidation, etc., there are many macroprocesses and mechanisms associated with the interaction, transformation, and movement of organized macrostructures of cells. However, all processes and mechanisms are controlled by the genome.

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7.9 Intracellular Functional Systems Cells have the ability to form certain groups of interconnectedly functioning macromolecules, organelles, and parts of the protoplasm depending on specific requirements. This is done through compartmentalization, which is a block principle in the internal organization and functioning of cells (Sect. 1.11). Functional systems are complex systems where the activity of constituent components determines the adaptive results they achieve. The distinction between certain functional systems is rather nominal, since the composition of the elements of these systems can vary significantly, depending on the conditions and the task. Nevertheless, several of the main functional cell systems can be distinguished according to the aims of the functions they perform. They are formed by directed interactions of organelles, parts of cells, and molecular complexes at the time they perform a certain task, and they serve to accomplish the functions of cells as integral systems. Such systems can coincide in purpose with similar systems within multicellular organisms or they can be characteristic only of cells. They may have the characteristics of individual free-living cells or cells within a system of tissues and organs. Conditionally distinguished structural and functional systems characteristic of the majority of cells include: (1) The system of nutrition and digestion. (2) The system for transforming substances and energy. (3) The excretion system. (4) The system for sorting and transferring substances. (5) The cytoskeletal system. (6) The system for receiving and transforming information. (7) The genome system. (8) The colloidal system constituting the cell’s contents. Other functional systems serving to carry out various tasks can be conventionally distinguished at different points of time during the cell’s life. For a better perception, we now look at the cellular system of nutrition and digestion, as an example. Its tasks are the absorption of food and its disintegration into small molecules. The source of nutrients for the cells in a multicellular organism is the surrounding intercellular medium. Taken as a whole, the intercellular medium makes up a fairly significant volume, for example, several liters in humans. A variety of organic molecules enter it from the blood and other cells. This liquid contains proteins, lipids, carbohydrates, amino acids, carboxylic acids, purine and pyrimidine bases, and more. Cell membranes have the ability to selectively absorb only the essential substances. For this purpose, the membranes have a special transport system. It includes pathways for passive selective transport of molecules along a concentration gradient or an electrochemical gradient, without the expenditure of ATP energy. This is how, for example, molecules of oxygen, carbon dioxide, amino acids, glucose, and sucrose are transferred. For some of them, there are special carriers on the membrane that recognize, bind, and transport these molecules via the hydrophilic channel. These are intricate, selective molecular transport systems that are part of a more complex nutritional system. In addition, there is a system of active transport of substances against the concentration gradient, which uses the energy of ATP and specialized carriers.

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A variety of cations and anions with very high osmotic activity are transferred in this way. Only small molecules are able to enter through the membrane transport system. Proteins, lipoproteins, chylomicrons, and other macromolecules and their complexes, with sizes comparable to the thickness of the membrane, are not able to pass through the membrane. For such nutrition, cells possess a special transfer system, called endocytosis. This is a complex active process of absorption of large molecules, particles, and microorganisms by a cell. Its varieties include pinocytosis, phagocytosis, and receptor-mediated endocytosis. Pinocytosis is the absorption of liquid and solutes with the formation of specific membrane vesicles. Phagocytosis is the absorption of large particles (aggregates of macromolecules, lipoproteins, cell parts). This involves the formation of large dense endocytic vesicles, or phagosomes. Phagosomes merge with lysosomes and form phagolysosomes, where the final disintegration of macromolecules takes place. Receptor-mediated endocytosis is characterized by the uptake of certain macromolecules from the extracellular fluid, these then binding to specific receptors on the membrane surface. The absorbed molecules also enter the phagosomes, after which they are digested in the lysosomes. Thus, the nutrient products enter the cell in already pre-digested form as molecules of amino acids, monosaccharides, low-molecular-weight carboxylic acids, and so on. They are transferred through the membrane and immediately included in the metabolism. Large macromolecules and their aggregates are digested in the intracellular digestive system, whereupon the nonspecific monomers are metabolized by the cell. Thus, the system of nutrition and digestion is the sum of interacting subsystems consisting of various cellular organelles and cell parts. This system accomplishes the major aim of providing the cell metabolism with all the necessary substrates. Meanwhile, the structural components of this system can simultaneously participate in the work of other functional systems. For example, membranes are part of the cell’s defense system: by not allowing harmful substances to pass through, they constitute a barrier to pathogens and certain toxic elements. Lysosomes are also participants in such functional systems, as they are involved in the process of phagocytosis and the disintegration of harmful substances and infectious agents. There is virtually no element in cells that performs only one function, and the number of performed functions is much greater than the number of existing organelles. Reversible reorganization of various cell structures (structural and functional blocks) into a certain functional system can take place in cells whenever required, against the background of constantly running basic processes. If the situation changes, then parts of the cell are easily reorganized to perform other tasks. Hence, molecular processes and interactions in all functional cellular systems are highly dynamic and purposefully interconnected. The cells of multicellular organisms possess a variety of both general and specialized functions, depending on the state of differentiation (differential expression of the genome). For example, certain functions are common to all cells: nutrition, respiration, excretion, catalysis, conversion of substances and energy, and some others. Specific functions are characteristic, for example, for cells of different tissues. In particular, muscle cells contract, nerve cells generate and conduct an electrical impulse, and epithelial cells form various functional layers and surfaces. Thus, the

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various possible ways of combining different macromolecules and organelles into intracellular systems endows cells with qualitatively new properties and functions that are not characteristic of the individual macromolecules and their complexes. This qualitative leap in evolution has led to the emergence of new characteristics of cells, i.e., the appearance of various functions as fundamentally new properties of biosystems. Thus, the specificity of cellular functions, such as nutrition, respiration, protection, motion, and so on, is due to the diverse compositions of macromolecules and the different structures, shapes, and properties of cells, all ensured by the genome.

7.10 Functional Associations of Cells A biological function is a specific controlled activity of a certain biological system, aimed at maintaining and preserving the organism. In mammals, there are more than two hundred types of variously differentiated cells. Each type is tailored to perform specific functions. Uniting with each other in various quantities and combinations, and acting in concert, they form a variety of systemic macroassociations, in particular tissues, organs, and body parts that perform functions beneficial for the body. Tissues are the primary level of functional cell association. These are systems of cells and intercellular substances, united by a common structure, functions, and origin. Hundreds of different types of cell compose the bodies of multicellular organisms. Four types of tissue are distinguished in animals, depending on localization, structure, and performed functions: epithelial, nervous, connective, and muscular. Here we also see that the combination of various cells into dense groups and their interactions determine the emergence of essentially new properties and functions of biosystems. Quantity turns into quality. Quality is transformed into properties, and properties into functions. Organs are the next level of functional cell associations. These systems consist of cells of different tissues, united with a view to performing specialized functions. This is a strictly ordered complex of cells and tissues of different types, formed in the process of evolutionary development. Organs are highly differentiated parts of the body, located in specific sites and performing particular functions. For example, the eye is the organ of vision, the ear is the organ of hearing, the heart is the pump for the circulatory system, and so on. Many organs simultaneously perform several functions. For example, among many other things, cells of the liver produce blood proteins, bile, and urea, and neutralize toxic substances. Organs consist of structural and functional units. These are individual cells or a group of organized cells capable of performing the main function(s) of an organ. For example, the functional unit of the liver is the hepatic lobule, in the lungs it is the alveoli, and in the kidneys it is the nephron. Organs combine into systems in the process of development to perform more complex functions. A physiological system is the next level of functional cell associations. It is a hereditarily fixed set of cells, organs, and tissues, connected by common functions.

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In particular, the cardiovascular system consists of numerous variously differentiated cells that form the heart and a variety of blood vessels and capillaries. The main functional task of this system is to ensure the movement of internal body fluids, thus enabling integration, regulation, and metabolism. Several physiological systems can be distinguished in mammals: nervous, endocrine, immune, digestive, cardiovascular, excretory, and others. A functional system is a dynamic group of physiological systems acting together to achieve an adaptive result useful for the body. In other words, functional systems are structural and functional blocks interacting with each other, jointly supporting optimal homeostatic parameters, thereby ensuring adaptation, survival, and reproduction. Depending on the needs of the body, functional systems can be formed by different constituent parts of physiological systems. For example, to restore blood pressure after blood loss, the cardiovascular, nervous, endocrine, excretory, and digestive systems interact in concert. The interaction of structural and functional blocks determines the high level of reliability of multicellular organisms. The features of the main functional biological systems of multicellular organisms presented here concern the relationship between structure and function, as well as the logic of the formation of such systems and the appearance of certain functions. The key here is the unification and interaction of various structural elements. Their union possesses completely new properties. This provides the basis for emergence of functions. Yet, such functions would never have become homeostatic without the expediency of their action for the body. Only the necessary functions are fixed in the genetic material of the genome and subsequently inherited. In addition, in mammals, each function is strictly controlled by the body through the nervous, endocrine, immune, and other systems. The sequence and interdependence of several functions aimed at achieving a certain result is a physiological process. For example, the process of respiration is provided by regulated sequential functions of the nasopharynx, trachea, bronchi, lungs, alveoli, blood, erythrocytes, and tissue respiration of cells in the various organs. The overall purpose of this set of functions is energy conversion. A multicellular organism is a complex heterogeneous supersystem of interconnected functioning cells, tissues, organs, and physiological and functional systems. This is a complex body that is the bearer of an individual life. All levels of its organization from molecular and cellular to the organs and other systems work collectively and are coordinated by the genome for the survival of a separate complex individual. The organism is built on the principle of hierarchy, i.e., the simplest components are included in more complex ones and determine their qualitatively new properties. In this way, for example, elements of the nervous or endocrine system can regulate molecular and cellular processes and functions. Analyzing the above, one can come to the conclusion that function, as a new property of living matter, appears only at a certain stage of its development. Individual molecules have no function. Neither protein molecules, nor nucleic acids, nor other organic or inorganic molecules have the ability to support themselves, their environment, or the system in which they are located, although they have various physicochemical properties. For example, proteins have a very strong primary structure, are

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amphoteric electrolytes, and possess buffering properties. Most proteins are highly water soluble. Aqueous solutions of proteins are stable, equilibrium, and homogeneous colloidal solutions. They are characterized by a low diffusion rate, impermeability through biological membranes, high osmotic activity, and high viscosity of solutions. Fibrillar proteins tend to form gels. Proteins are very stable under physiological conditions, but they are capable of controlled reversible changes in their conformation. Now, none of the above can be considered to be functions; they are only properties. However, on the basis of exactly these properties, as well as interactions between themselves and other molecules, proteins do perform various functions in the body. In particular, structural, catalytic, contractile, regulatory, protective, transport, and many functions. Thus, properties “turn into” functions under certain conditions. For example, the structural function of proteins appears after they are combined into certain organized complexes and systems based on chemical and physical interactions. In particular, biological membranes are formed in this manner. These are ordered complexes of lipid and protein molecules with a definite qualitative and quantitative composition, combined on the basis of polar and hydrophobic interactions. Individual molecules of this complex do not yet have functions; it is only their organized combination and interaction that provides a range of different directed membrane processes. In this sense, functions emerge. This results in the ability of membranes to perform the following functions: barrier, transport, energy, receptor, communicative, and more. In addition, certain conditions are required for the functions of membranes to manifest themselves. In particular, an aqueous liquid medium, neutral acidity, and moderate temperature and pressure are required. The enzymatic functions of proteins are also manifested only in an aqueous environment, at moderate temperatures, in the presence of substrates, and so on. Hence, organisms are complex ordered cellular systems with several levels of organization. The main parts of multicellular living bodies are molecules, cells, tissues, and organs. The chemical, physical, and biological properties of structural units and their combinations determine their various functions in specific environmental conditions (aqueous environment, acidity, temperature, etc.). Both unicellular and multicellular bodies in the process of life are faced with the same survival challenges. They need to grow and develop, maintain their integrity and autonomy, reproduce, eat, breathe, and so on. This determines the presence of similar structures in them, different in construction, but responsible for fundamentally the same functions. For example, unicellular organisms have peculiar organs of movement (flagella, cilia, pseudopodia), digestive organs (digestive vacuoles), excretory organs, osmoregulatory organs, and defense organs. Organs performing exactly the same functions are also found in higher animals. It should be noted that functions and processes are derivatives of structure. Obviously, a certain material structure must first appear and only then, depending on the conditions, can the function manifest itself. For example, the function of muscle contraction requires the presence of an actomyosin structural complex. Naturally, the features of the function are completely determined by the properties of the structure. The structure determines the size, shape, state of aggregation, and reactivity of the

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given system, that is, it is a stationary and potential characteristic of a living body. And a function is a dynamic characteristic reflecting directional changes in the structure of a biosystem. Functioning is the directed and regulated biological, chemical, or physical process of change in the stationary characteristics of systems in time. The correspondence and interconnection of structures and functions is characteristic of absolutely all levels of organization in any living organism, and this is explained by the laws of development and evolution. The functions of inanimate objects and systems are not directed and not controlled by themselves (except for machines created by man), whereas the functions and processes of living systems are precisely controlled by the elements of these systems and aim first and foremost at maintaining these systems’ own stability. The genome controls all the elements of functioning systems through differential expression in different parts of the body, strictly monitoring the protein and enzymatic composition and, if necessary, quickly changing it. Thus, there is a clear correspondence between structures and functions at different levels of organization, from organismic to molecular. Moreover, each structure is optimal and appropriate for performing a specific function, and this is natural for all living organisms. There is a clear connection between the level and complexity of the organization of biological structures and the presence of their respective functions. Specific physiological activity, controlled by the genome, appears at a certain stage in the development of biological systems on the basis of the physicochemical and biological properties of its elements and structures, aimed at preservation, maintenance and reproduction of living organisms.

7.11 Summary The life of cells is, on the one hand, a set of specific processes that organize matter. On the other hand, the processes themselves are a consequence of organized matter. The basis of both the structure of living bodies and the processes is the phenomenon of controlled interaction of molecules. Selective biological catalysis is a strategic mechanism for almost all life processes. The main merit of enzymes is to ensure the possibility and increase the likelihood of a strictly defined set of biochemical and biophysical processes necessary for the construction of living bodies and their functioning. Intracellular metabolism and the transformation of substances and energy are the source of the “life force” and the basis for all molecular-genetic and functional processes. The vitality of highly organized living bodies is based on the antientropic processes of overcoming the chaos that spontaneously arises in biological systems. Many functions, processes, and mechanisms of living bodies are due to electrical phenomena. Cells can be viewed as microelectronic physicochemical machines that work and maintain their integrity due to electromagnetic forces and interactions. Most biological processes and mechanisms are due to quantum mechanical interactions of molecules and elementary particles. Informational-genetic processes are simultaneous, parallel, interconnected transformations of the information and

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genetic material of genomes, which manage the very foundations of life. Along with the numerous molecular microprocesses, many cellular macroprocesses and mechanisms are associated with the interaction, transformation, and movement of organized cell masses. The properties of biological systems give rise to the functions that support and develop these systems. Parts of cells, organelles, and molecules and their complexes possess numerous options for combining into dynamic structural and functional systems to perform a wide variety of complex functions. All the listed sources of viability of living bodies are controlled and operated by their genomes.

Part V

Genesis and Evolution

Chapter 8

Genesis

8.1 The Probability of Life Studies of various phenomena have shown that there are two types of dependence between conditions and the possibility of the onset or non-occurrence of an event. In some cases, the phenomenon always naturally manifests itself, while in others only a multiple repetition of conditions can lead to the manifestation of the event. Such an event is called random. However, random events are not causeless; there are necessarily conditions and forces that cause their manifestation. But a combination of many independent circumstances is necessary for the manifestation of such an event, and this significantly reduces its probability. Many events in nature are related. Moreover, individual phenomena are a consequence of certain events and at the same time can be the cause of the next. It is often difficult and even impossible to trace the connection between all conditions and events. This is especially true for biological objects, which are very complex systems with billions of interactions taking place at the same time. Trillions of different molecules experience millions of random collisions per second due to thermal motion in an aqueous medium. Cells are complex, highly ordered molecular systems in which strictly defined processes run at precise sites and in specific directions. The probability of the appearance and existence of such systems is extremely low. It is highly improbable that a strictly defined set of molecules (from an innumerable range) would concentrate in a microscopic space, isolated from the external environment, in strict quantitative and qualitative proportions and arranged in a clear hierarchical order. But unlikely does not mean impossible. Genetic and other information programs significantly increase the likelihood of certain material events, due to which unlikely phenomena do not just happen, but are stably reproduced in living systems. In particular, special structural and functional proteins, including enzymes, are synthesized in accordance with specific genetic information. Structural proteins and other molecules are organized into certain probabilistic macrostructures of a cell, for example, organelles, according to the laws of chemistry and physics. Enzymes and © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_8

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other functional proteins guide biochemical processes from millions of possible directions to only those few that are necessary for the cell. It is important to understand clearly that the incredible complexity of multicellular bodies is formed only in the process of development. “Incredible structures” are built step by step from fertilized eggs, gradually, according to the laws of development, on the basis of genetic programs and the molecular mechanisms of their implementation. It is the mechanism of development under the control of the genome and selective enzymatic reactions that makes it possible to bring about the unlikely events that cause the appearance of very complex living bodies. Another condition and reason for the implementation of unlikely events in living organisms is the purposeful use of energy. The fact is that, according to the laws of thermodynamics, destruction processes that do not require any energy consumption are more probable, whereas any processes for creating order require the application of certain forces and the use of energy. Thus, the creation and maintenance of ordered biological systems requires an inflow of energy to certain material structures and processes. Targeted use of energy is provided by enzymes, which purposefully supply it only to the necessary biochemical reactions. An organized biological system can ensure the course of its own unlikely events by selectively providing these events with energy. The likelihood of certain chemical reactions is significantly increased in cells due to the genetic selection of enzymes. These “molecular machines” perform several highly important things. First, they catalyze strictly defined processes, significantly increasing their probability, and, secondly, they increase the rates of initially unlikely processes by factors of thousands. In this case, the “all or nothing” principle is observed: if there is an enzyme then there is a highly pronounced stochastic process; but if there is no enzyme, there is no process. The likelihood of the spontaneous formation of specific cellular macromolecules is extremely low. Consider, for example, the probability of formation of one of the smallest proteins—insulin. It consists of 51 amino acids, which means that the probability of combining 20 different amino acids in the required, unique order is just one in 2051 . And this is just one out of 2.6 × 1066 possible variants! Moreover, in order for insulin to become activated, it needs to be given a certain structure and spatial shape in the process of post-translational modification and folding. For this, the polypeptide must be precisely and purposefully cut by enzymes into several parts and only two specific polypeptide chains must be connected with disulfide bonds at particular sites. Then it must be given a unique biologically active spatial form. The likelihood of getting such an result by chance is extremely small, and is estimated at one in a trillion. That is, the probability of the existence of each of the tens of thousands of specific proteins of living organisms is virtually zero. And yet, proteins, even those consisting of hundreds of amino acids, exist in abundance. Furthermore, they constantly reproduce at tremendous rates and are successfully inherited over millions of years and millions of generations. Given the above considerations, we may say that cells and organisms are biological systems that create conditions for the transformation of random events into real ones. Living bodies are extraordinary amplifiers of the probability of random events.

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Individuals of various species are also a matter of chance. For example, one can estimate the likelihood of the birth of a given human individual. In this case, only the following conditions and circumstances will be considered (the figures below are highly approximate, but reflect the basic idea): 1. The chance of meeting partners. For example, the probability of a specific man and woman meeting (if their numbers are equal) in a city with a population of two million is approximately 1 out of 1012 . 2. The probability of fertilization of a particular egg by a particular sperm. A woman has several tens of millions (107 ) of variants of allele-varying egg cells in her ovaries, each of which has a chance of maturing and being fertilized. A man produces up to 1011 variants of allele-varying spermatozoa in 50 years of reproductive activity. This means that the probability of an encounter between two specific gametes is approximately 1 out of 1018 . 3. The randomness of crossing-over processes during meiosis when gametes form. The haploid set of chromosomes of humans contains approximately 3.2 × 109 nucleotide pairs. This means that the probability of their recombination upon contact with homologous chromosomes (if only a single crossing-over event is considered) is approximately 1 out of 1019 . 4. The randomness of the combination and divergence of chromosomes into separate gametes during meiosis. The number of possible combinations can be up to 105 . Thus, just the obvious circumstances taken into account here already reduce the likelihood of the birth of, for example, Gennadiy Zhegunov to 1 out of 1044 , which makes it virtually impossible (only around 1011 of human individuals have ever lived on Earth). However, he exists in reality, and is writing this book, despite the almost absolute impossibility of this phenomenon. Likewise, in all other sexually reproducing living beings: individuals appear by chance, without being asked, and regardless of their will. All kinds of DNA mutations and recombinations are examples of random events that constantly occur in cells. Mutations can be caused by various factors that unpredictably affect any of the trillions of base pairs. The consequences of such mutations are also unpredictable for the organism and can be neutral, lethal, favorable, or unfavorable. Since mutations are a source of various forms and new traits for natural selection, it is clear that the direction of the evolutionary process is completely random and unpredictable, and will most likely correspond to certain environmental conditions. The origin of life through chemical and then biological evolution is also a lowprobability process. It is hard to imagine that from a rather limited composition of simple “non-living” molecules, there suddenly appeared organic substances, then large polymers, and then “living” macromolecules of nucleic acids and proteins with emergent properties. It is difficult to imagine the accidental appearance of a selfcatalyzing “replicator” with an extraordinary ability to reproduce. It is even more difficult to imagine the emergence of an autonomous, closed, ordered space saturated with unique molecules, biocatalysts and organized structures, capable of resisting the very physical phenomenon of entropy.

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However, all the same, the origin of living bodies can be explained on the basis of the laws of nature and scientific data (which is described below), without involving any supernatural forces. It should be borne in mind that evolutionary experiments were carried out in nature by trial and error in an enormous volume including the entire surface of the Earth for hundreds of millions of years. Therefore, the probability of the occurrence of random processes of self-organization and evolution of molecular systems under favorable conditions would have increased significantly over time, and even such small chances could well be realized in reality. In the long process of genesis and development, the structurally functional achievements of living bodies were fixed by nature in their genetic programs, which, together with the genome, began to be passed on to descendants. And it was the consolidation and transmission of genetic information that turned almost incredible events into a stable, immortal phenomenon of life.

8.2 The Main Stages of Phylogenesis In this chapter, we present the alleged stages of the emergence of life. However, little can be said about the specific ways and mechanisms of their implementation. That is, we can still try to imagine “what could have happened”, but we are still a long way from being able to say “how exactly it happened”. The phenomenon of life in the form of a variety of unicellular and multicellular organisms and their systems has existed on Earth for about 3.5 billion years, which is only one billion years less than the age of the Solar System. It is believed that life arose from the elements of inanimate nature on the basis of natural laws, due to chemical evolution, spontaneous aggregation, interactions, the gradual complication of molecules, and the self-organization of their dynamical systems (see Chap. 2). Studies of fossil remains, comparative studies of modern organisms, cells, and molecules, genetic analysis, and so on, provide information on the main stages of phylogenesis, with each stage introducing the qualitatively new emergent properties of matter. Emergence is the appearance of new and unpredictable properties in complex developing systems as a result of the interactions of its components. This is a sudden manifestation of revolutionary properties at various levels in the development of the ever-increasing structural and functional complexity of these systems.

8.2.1 Emergence of the Pattern of Organization of Living Bodies In an aquatic environment, in the absence of oxygen, at liquid water temperatures and under the influence of atmospheric electricity, amino acids, carboxylic acids,

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carbohydrates, nucleotides, etc., are formed from inorganic substances (H2 O, CO2 , N2 , H2 ) as a result of various chemical and physical processes. At this stage, a fundamentally new group of compounds arises on the basis of carbon molecules. These are organic substances that have qualitatively new properties compared to their predecessors. More complex macromolecules are formed from the basic organic substances as a result of chemical evolution via polymerization: polypeptides, polynucleotides, small RNAs, carbohydrate polymers, lipids, etc. These groups of biomolecules possess a number of properties essential for the construction of complex spatial structures, and storage and transmission of information. Macromolecules combine, interact, and form stable complexes—coacervates. These are isolated, complex, ordered colloidal systems capable of resisting environmental factors for a certain time, maintaining their organization and controlling the flow of substances and energy that passes through them. Certain RNA molecules of coacervates acquire the ability to catalyze, as well as the ability to reproduce themselves via complementary matrix copying. This is how the first mechanisms of reproduction appear along with the carriers of the mechanism of nucleotide recording and the matrix principle for transferring genetic information. The “RNA world” thus emerges, formed by ribozymes that are able to reproduce copies of themselves and form colonies. Some RNA molecules acquire the ability to transmit information to polypeptides and purposefully synthesize proteins. This gives rise to the protein-based structural and functional diversity of coacervates and their contents, and provides the source for the natural selection. The evolution of proteins leads to the appearance of enzymes. This increases the likelihood, selectivity, and rate of the necessary biochemical reactions by factors of thousands, and orders and directs the flows of matter and energy. Enzymes enable the emergence of metabolism, the purpose of which is to exploit matter and energy from the external environment, transforming them into the desired forms and using them for self-repair and maintenance of integrity. At this stage there appears a “biochemical accumulator” of energy in the form of ATP, which also becomes a conjugating factor for exothermic and endothermic reactions inside coacervates. The co-evolution of nucleic acids and enzymes in colloidal systems leads to selforganization and the emergence of DNA, as well as the molecular mechanisms of replication, transcription, and translation. The most important processes of catalysis and matrix synthesis are combined. The function of the primary carrier of genetic information is taken on by DNA molecules capable of replication, and RNA becomes an intermediary in the chain of information transfer DNA → RNA → protein. At this stage arise the fundamental principles of organization of a genome and its phenotypic framework. Colloidal systems, capable of maintaining organization and self-renewal, form membranes and the surface apparatus for protection and interaction with the external environment. This results in the emergence of stable autonomous bodies—probionts. A single group of ancestors thus appears, common ancestors to all future organisms that today contain a whole range of nucleic acid and protein complexes and display

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many different attributes and properties. That is, billions of years ago, along with the precursors of cells, the pattern of organization of living bodies was already created. This was a fundamentally new molecular system—a living system, which necessarily consisted of two complex, mutually integrated blocks: (1) the genome (nucleotide memory)—life control systems; and (2) the phenome (protein operating unit)—the executive system of the genome (see Sect. 2.6). Once created by nature, the principle of organization of living bodies was reproduced and cloned for many millions of years along with nucleic acids and the cytoplasm of cells in the process of reproduction. The following billions of years did not make any fundamental changes. Using only slight variations in the qualitative and quantitative composition and the organization of nucleic acids and proteins, evolution has built an enormous number of species of living bodies, along with the mechanisms and processes required for their vital activity. Nevertheless, all of them are hereditary carriers of the pattern of organization that was first created by nature billions of years ago.

8.2.2 Emergence of Living Bodies and Individual Life Several billion years ago, the first fully-fledged unicellular organisms appear, viz., archaea and bacteria. They already have all the basic characteristics of living bodies: a well-defined structure and shape, the ability to carry out autotrophy, a stable metabolism, and the ability to self-repair and reproduce. And most importantly, they possess a command system for storing and operating information in the form of a genome, as well as an executive system for its support and protection in the form of a phenome. Their autonomous bodies have permanently secured the ability to survive for a long time through self-recovery and the ability to reproduce for indefinitely many generations. The emergence of a variety of prokaryotic cells, which are autonomous self-repairing self-reproducing biosystems, announced the next emergent evolutionary event—the emergence of living bodies. And since each living body possesses individual qualities, they can be considered the first bearers of individual life. Table 8.1 provides a list of the main features of prokaryotic cells as compared to eukaryotes. A prokaryotic cell is more “primitive”, but it still has a rather complex structure, which allows it to be considered as a fully-fledged living body. The survival and evolution of prokaryotes is primarily ensured by the use of many variants of trophic metabolism in different habitats. Consequently, the main direction of the evolution of prokaryotic organisms was the search for optimal pathways of trophic metabolism, while the evolution of eukaryotes aimed at complicating morphofunctional adaptations. In this regard, the highest evolutionary achievements of prokaryotes can be seen precisely in their metabolic activity, which has reached amazing levels of perfection. Although the haploid genome of prokaryotes is relatively small and simple in structure, the variety of types and forms of metabolism in their cells significantly exceeds the biochemical diversity of eukaryotic cells.

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Table 8.1 Comparison of a range of characteristics of cells in three domains of the organic world Characteristics

Bacteria

Archaea

Eukarya

Ploidy

Haploidy

Haploidy

Diploidy

Genomic DNA

Circular

Circular

Linear

Introns

No

Yes

Yes

Histones

No

Yes

Yes

DNA polymerase

1 type

1 type

3 types

Nucleus

No

No

Yes

System of intracellular membranes

No

No

Yes

Ribosomes

70S

70S

80S

Organelles

No

No

Yes

Cytoskeleton

No

No

Yes

Chemosynthesis

Possible

Possible

Absent

Nitrogen fixation

Possible

Absent

Absent

Multicellularity

Possible in primitive form

Not known

Highly developed

Reproduction Cell division

Asexual Mitosis

Asexual Mitosis

Asexual and sexual Mitosis and meiosis

Prokaryotes “invented” all the vital biotechnologies, including enzymatic catalysis, photosynthesis, nitrogen fixation, respiration, and nutrition. In particular, prokaryotes are characterized by bacteriorhodopsin and anoxygenic photosynthesis, various pathways of chemosynthesis, nitrogen fixation, methanogenesis, most of the pathways of anaerobic respiration, specific ways of using C1 and C2 compounds, and the vast majority of types of fermentation. Various types of bacteria and archaea are able to feed on methyl alcohol, carbon monoxide, methane, and formic acid, and also carry out photosynthesis without chlorophyll, without releasing oxygen, synthesize organic substances from inorganic ones in the absence of light, “breathe” oxides of iron, manganese, arsenic, nitrates, nitrites, sulfates, and so on. Then, evolution of photosynthetic prokaryotes led to the appearance of cyanobacteria—the first microorganisms capable of carrying out oxygenic photosynthesis. Cyanobacteria use photolysis of water, a generally available substance, as a source of electrons and protons. Oxygen becomes a byproduct of photosynthesis. A largescale process of oxygen accumulation thus began in the Earth’s atmosphere. An ozone layer formed around the planet, thus protecting living organisms from the destructive effects of the severe ionizing radiation from space. It was largely due to this that the further evolution of life became possible. As a result of the accumulation of oxygen in the atmosphere, a number of prokaryotic cells acquired the ability to carry out aerobic respiration, i.e., the use of oxygen for oxidation and extraction of energy from nutrients. This highly efficient metabolic pathway significantly expanded the energetic capabilities of organisms, leading to

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the emergence of heterotrophic nutrition, a new range of functions, more complicated levels of organization, and the adaptation and further evolution of living bodies. Therefore, having an elementary unicellular structure and a single set of chromosomes, prokaryotes have achieved spectacular results, especially regarding the development of ways to adapt to various habitats, physicochemical conditions, and nutrient and respiratory substrates. This has ensured their wide distribution and successful survival for several billion years. Their ubiquitous dissemination has provided the basis for the gradual formation of a system of haploid prokaryotic life, a network covering the whole of planet Earth. Emergence of eukaryotic cells. The next emergent evolutionary event was the origin of diploid eukaryotic cells. There is a hypothesis about the origin of eukaryotes, wherein the combination of a nucleus, diploid genome, chloroplasts, and mitochondria are seen as the result of symbiogenesis (see Sect. 8.4.6). The main feature of eukaryotes is the presence of a nucleus. But there are also a number of other intracellular structures, whose functions determine a range of special features of eukaryotes. For example, the cytoskeleton is a system of mobile protein filaments located in their cytoplasm. It was the development and contribution of a mobile cytoskeleton that led to the emergence of a system of intracellular membranes (including the nuclear envelope), phagocytosis, mitosis, meiosis, and sexual reproduction. It was the cytoskeleton that provided the ancient eukaryotes with the ability to phagocytose bacterial cells, which were gradually transformed into mitochondria and chloroplasts. In general, the fundamental features of eukaryotic cells are as follows (see Table 8.1): (a) the presence of a separate nucleus—a finely organized system of genome localization; (b) the presence of a large diploid genome; (c) the presence of a complexly organized dynamic cytoskeleton; (d) the presence of a branched system of membranes; and (e) the presence of organelles. Of particular importance are the fundamental features of the eukaryotic genome, such as diploidy, a large genome, the linear shape of the chromosomes, no frame shifts during transcription, and DNA containing exons and introns, wound on histone proteins, and forming a chromatin network. Diploidy was an extremely important acquisition of eukaryotes. It enabled them to significantly increase their resistance to mutagenic environmental factors and created the basis for genetic recombination during reproduction. This provided a colossal variability in their offspring, which significantly increased the chances of overcoming the “filter” of natural selection, thereby ensuring the evolutionary process and overcoming the pressure of entropy factors. Eukaryotic cells can live independently, unite in colonies, or form multicellular bodies, where they form numerous tissues and organs, performing a wide range of functions and forming multicellular structures with various configurations, content, and levels of organization. Yielding to haploid prokaryotes in a variety of metabolic adaptation strategies, diploid eukaryotes have nevertheless mastered almost all the ecological niches on our planet. To do this, they use other strategies and mechanisms of adaptation. In particular, multicellularity and differentiation of cells into various structural and

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functional units. The emergence of eukaryotes has significantly increased the life potential of organisms and their ability to adapt, survive, and spread. Today, the massive diversity of the totality of prokaryotic and eukaryotic cells has formed a huge biomass of living bodies that have penetrated into all possible geophysical systems of our planet. The primary phenosphere was formed, qualitatively changing the Earth’s landscape in a couple of billion years. The planet’s surface acquired soil and the atmosphere became saturated with oxygen and carbon dioxide. The conditions were created for the emergence of more complex organisms. Emergence of multicellularity. The next key emergent event was the emergence of multicellular eukaryotic organisms. Approximately 1.2 billion years ago, on the basis of a long evolution of the simple eukaryotic cells and their colonies, primitive multicellular organisms finally appeared. The emergence of multicellular organisms was initially associated with the unification of unicellular organisms in colonies, which significantly increased the adaptive capabilities of each individual cell. Gradually, specialized cells appeared in the colonies, performing specific functions, which increased the chances of the adaptation and survival of each cell and the whole “organism”. Further evolution was associated with the emergence of the ability of the genomes of eukaryotic cells to engage in differential expression, providing a selective and dosed use of genetic information (see Sect. 2.6), as well as the ability of differentiated specialized cells to combine and function together. Then there emerged a special line of reproductive cells, capable of meiosis, which made it possible to multiply through gametes after recombination of the hereditary material of genomes. Special intercellular contacts and complex interactions between the cells came into play, and this contributed to the formation of the first multicellular organisms. One of the key stages of evolution on the way to multicellularity was the appearance of the epithelium, where cells form layers that separate the internal environment of the organism from the external environment. Nerve cells and muscle cells were also important, and therefore appeared in animals in the very early stages of their evolution. All these cell types can be found today in very primitive modern organisms, for example, in the hydra (Fig. 8.1). That is, the evolution of higher animals created a huge number of different specialized cells, along with various options for ordering them and methods for coordinating them. In particular, mammals have over 200 of differentiated cells types. The further evolution of multicellularity followed the path of the formation of specialized tissues and organs, as well as exploring ways of coordinating their activity. For example, animals have developed several types of tissue and dozens of organs. The nervous and endocrine systems appeared, consisting of hundreds of types of cells that perform many functions, including the function of coordinating the work of all the organs, tissues, and cells. A very complex immune system also formed. A variety of immune cells appeared, capable of phagocytosis and the production of millions of different antibodies, which provided better and better protection of multicellular organisms from the penetration of foreign bodies. The combination and interaction of cells formed stable multicellular associations, within which emerged a distribution of functions and gradual specialization among

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Fig. 8.1 One of the first multicellular organisms, whose genome has survived to this day. Depiction of a hydra and its cells. The genome acquired the ability to engage in differential expression, bringing about the polyphenotypicity of cells. During this period, the genome’s ability to build complex colonies of different sizes and shapes was realized by regulating the dosage and direction of information dissemination. 1—mouth, 2—nerve cell, 3—oocyte, 4—spermatozoon, 5—myoepithelial cell, 6—digestive cell

the cells. The efficiency of nutritional processes increased, and an ability to withstand unfavorable influences of the internal and external environment also emerged. The survival rate increased, and it became possible to carry large reserves of water, which gave them the potential to master new ecological niches and habitats (and in particular, access to land). In the gradual process of development, on the basis of differential gene expression, a gradual complication of the structural and functional organization of multicellular organisms arose, with specialized cells, tissues, and organs, which created conditions for the formation of millions of different living bodies, differing widely from each other, depending on their adaptation to their particular habitat. A variety of plants, fungi, and animals appeared. Higher animals developed fundamentally new abilities and functions: visual, hearing, nervous, immune, and other systems, the ability to grow and develop, memory, and much more. The evolution of multicellular organisms in various conditions on the Earth, powered by mutations, recombinations, hybridization, and natural selection have led to the emergence of millions of different species of living organisms that have populated almost all possible ecological niches on Earth. Approximately 500 million years ago, the evolution of genotypes and phenotypes led to the emergence of chordates and then vertebrates with bilateral symmetry, an axial skeleton, and a brain. In the course of their long evolution, animals mastered the terrestrial habitat (amphibians), amniotic development (reptiles), and warm-bloodedness (birds and mammals).

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The increasing complexity of the brain of higher vertebrates led to the emergence of complex social behavior, refined forms of caring for offspring, and the development of individual identity. Specific elements of intellect evolved and several million years of anthropogenesis finally resulted in the appearance of Homo sapiens about 100 thousand years ago. The above sketch of the path of emergence and progressive development of life explains the uniformity in the principles of structure, molecular composition, common metabolic pathways, reproduction, and so on, inherent in all the millions of species of organisms currently existing on Earth and all those that have lived previously1 . The evolutionary acquisitions of multicellular organisms allowed them to raise the potential of individual life even higher, to improve adaptive capabilities and the efficiency of survival, and finally also to shape the modern form of the unified planetary system of life. Hence, an almost infinite number of species of living organisms evolved from simple unicellular ancestors. Or, rather, from our point of view, an infinite variety of species of genomes evolved from the genomes of unicellular ancestors. Each new species of genome is strictly adapted to its habitat and way of life through its specific phenotypic framework, and the process of evolution itself is continuous and directed into the boundless future.

8.2.3 Emergence of the Planetary System of Life The next emergent event was the formation of the planetary system of life (see Chap. 2). As a result of continuous reproduction and evolution, a vast heterogeneous community of living organisms has formed on Earth. Trillions of very diverse living bodies have spread across almost the entire planet, mastering almost all its ecological niches and using its resources for their own purposes. As already noted in Chap. 2, the entire set of living bodies on the planet forms the planetary system of life, which consists of the global phenome and the global genome (Table 2.3 and Fig. 2.5). The global phenome, or phenosphere, is a material system consisting of all living organisms that exist on Earth. The global genome, or genosphere, is the set of genomes of all living organisms. It is an information system that covers the entire planet (Table 2.2 and Fig. 2.5). It contains all the genetic information of all living organisms on Earth. Indeed, it forms a single informationalgenetic field of life on Earth. The expression of individual genomes determines the specific manifestations of individual living bodies. Therefore, we can say that “all

1

There is another idea, known as the panspermia hypothesis, according to which life may have been brought to Earth from space in the form of spores or microorganisms. However, this does not deny the further evolution of life on our planet and only transfers the initial stages of its emergence to other cosmic bodies.

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life on Earth” constitutes an extensive system, the phenosphere, which is a product of the differential expression of the genosphere. These systems are mutually integrated and form a single planetary system of life, i.e., a set of all interacting and interconnected genomes and phenomes. They are united into a comprehensive system by the interdependent coexistence of matter and information. Thus, the progressive reproduction, evolution, and distribution of organisms over virtually the whole planet has led to the stable existence of a huge self-reproducing, self-sustaining planetary system of living organisms (Table 2.1). Its most important characteristics are as follows: • The planetary system of life is represented by the totality of all interdependent living bodies on Earth. • The units of organization of this planetary system are living bodies possessing individual life. • The system of life has existed for billions of years in an inextricable interconnection with the planet. • The planetary system of life is the constancy of the variety of dying and reproducing units of life. • The planetary system of life has been immortal since the moment of its genesis. • The planetary system of life is characterized by heredity, variability, and evolution. • The immortality of the planetary system of life lies in its dual nature, viz., the coexistence of material bodies and information. While material bodies are invariably destroyed according to the laws of physics, the information component of their genomes moves constantly and without loss through space–time thanks to the process of reproduction, retaining the ability to recreate a new body. Thus, billions of years ago, a stable self-renewing system of living bodies appeared on the Earth. Its units of organization were unicellular and multicellular organisms, consisting of genomes in a phenotypic framework. The essence of this evolutionary leap was the emergent appearance of a long-lived global system of genomes and body processes for their maintenance.

8.2.4 The Emergence of Death and Immortality Life originally arose in conditions of chaos, thermodynamic destruction of the material world, and at the same time, spontaneous self-organization. Organized systems are destroyed particularly quickly (Sects. 1.10, 2.4, Fig. 2.2). That is, formation, functioning, destruction, and collapse are initially an inseparable property of any organized system on Earth, including biological ones (see Chap. 11). Consequently, biological systems are organized and ordered, but at the same time non-equilibrium and collapsing according to the laws of thermodynamics. They can exist for some time, but only by attracting matter and free energy from the external environment for self-recovery. It is to such dissipative systems that cells

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and multicellular organisms belong. They necessarily gradually wear out, age, and naturally perish. But since they are living bodies, we call their collapse a death in order to distinguish this phenomenon from the general processes of disintegration. Thus, we can say that every living body possesses not only an individual life, but also an individual death. Spontaneous destruction is a tragic event to any organism, but it is of great importance for the progress of the planetary system of life, as it removes the old, worn out, and defective components from the system. This means that their removal requires no extra effort and no expenditure of either matter or energy from Nature. All living bodies are destroyed and die spontaneously. Material resources and energy are used only at the stage of controlled creation and for maintenance of vital activity (Fig. 11.4). Living bodies also die en masse due to a variety of other negative natural causes. In particular, from infections, diseases, poisoning, hunger, thirst, predation, disasters, and much more (see Chap. 11). In addition, it turns out that, despite the inevitability of natural death, Nature has also forcibly genetically limited the duration of life of each individual (see Chap. 11). Moreover, life has no means and methods to cope with this hereditary death sentence. Nature has approved the maximum lifespan for all types of organisms and no one is allowed to cross this red line. The immortal genome leaves no chance for its phenotypic framework to exist longer than it wants. That is, Nature has also genetically limited the lifespan of individuals. This is necessary for the inevitable change of generations, which is of critical importance for the evolution of species, the exchange of living bodies, and the renewal of the planetary system of life (see Sect. 9.7). Therefore, death, like reproduction, works only in favor of the planetary system of life, even though death is a tragic ending for the particular life of an individuum. It can be said that the life of an individual is subordinate to the planetary system of life and is its servant, whereas the whole organism of the planetary system of life uses its constituent living beings to extract material resources and energy from the external world for its own use and for its own selfish purposes of immortality. Hence, living bodies appear, develop, multiply, grow old, and die, in every case and forever. But their genomes do not disappear without a trace, provided that organisms leave behind offspring carrying the renewed genome of the species. This means that the genome is not subject to death, but rather enjoys endless evolution. Therefore, the death of particular individuals is of absolutely no importance either for their permanent genomes, or for the immortal planetary system of life they constitute. Once again, it is important to note that genomes do not disappear with the death of individuals. The death of living bodies is countered by the preliminary mass reproduction of their genomes. Their reproduction is based on DNA replication, duplication of genome bodies, and their subsequent transfer to other living bodies. That is, it is genomes that act as the main characters on the stage of life, not disappearing even after the death of living bodies. Only they possess the property of permanence, which is passed on to subsequent generations, ensuring the immortality of the planetary system of life. This means that reproduction is in fact the process of copying of genomes by themselves and their transit into daughter organisms using the properties

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of the living bodies in which they live. Mortal bodies are doomed to perish, but for genomes this does not matter. Death appears as an inevitable stage of their renewal along the path of immortality. Thus, immortality came into being at the very moment when the ability to reproduce emerged. However, this is not the immortality of living bodies, but the immortality of their genomes.

8.3 The Role of Temperature Rather low biological temperatures are the key condition for the emergence and manifestation of life (see Sect. 1.8). Once again, an important characteristic of the temperature range of life should be emphasized: basically, life manifests itself only within an extremely narrow range of temperatures (generally between 0 and –45 °C), which is very close to the lower limit of temperatures possible in nature. At such low temperatures, the chemical bonds of organic molecules are stable, which ensures the sustained existence of complex substances. At the same time, many chemical reactions are thermodynamically impossible or can only proceed at extremely low rates, which would be unable to ensure the manifestation of life. Only the presence of biocatalysts (enzymes), which deliberately weaken chemical bonds and accelerate selected reactions thousands of times, can ensure implementation of the necessary biochemical processes. It is biological catalysts that enable the specialization of the world of biochemical reactions that determine life. Through the high rates and specificity of the reactions they facilitate, enzymes isolate a limited set from the virtually unlimited number of possible reactions between countless molecules. Consequently, it is enzymes that create the conditions for the occurrence of processes that would otherwise be unlikely at the temperatures of life and hence enable the key phenomena. Temperature-symbiotic evolution. As noted earlier, our planet was initially subject to a long chemical evolution of substances in a liquid aqueous medium based on the thermal motion of myriads of molecules and their interactions. This led to the spontaneous emergence of organic matter. The relatively low ambient temperatures (from 0 to 45 °C) would have ensured sufficient stability for the chemical bonds of organic substances, but prevented many spontaneous reactions. We assume that periodic fluctuations in the temperature of liquid water from 0 to 100 °C in the places where life began (for example, geysers, underwater “black smokers”) were among the critical natural tools for the evolution of macromolecules and their complexes (Fig. 8.2). In particular, this would have led to manifold amplification and modification of nucleic acids depending on the complementarity of their strands. Hence, DNA would have disintegrated at 90 °C into two template chains, and after cooling, daughter chains would have been built on them from the nucleotides in the surrounding medium (similar principles are used in the laboratory method of polymerase chain reaction, PCR). It can be assumed that this phenomenon was the basis for the emergence of the processes of replication and reproduction of DNA molecules, and then the phenomena of heredity and variability.

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Fig. 8.2 A hypothetical scheme showing the possible pathways of temperature-symbiotic evolution and the emergence of the common ancestor of all living bodies. Nucleic replicators are ribozymes capable of both catalysis and template synthesis of their own kind. Nucleoprotein replicators are already represented by double-stranded DNA molecules in a complex with proteins. They are able to reproduce, but not to withstand extreme environmental factors. The membrane-covered coacervates are capable of self-regeneration, but not reproduction. Their combination into one system with DNA leads to the formation of protobionts, common ancestors, capable of both self-regeneration and reproduction. The common ancestor combines these two properties and immediately constitutes both a living body, and then a system of living bodies

RNA molecules would also have changed their conformation under the influence of temperature fluctuations, forming new variants of complementary bonds within one strand, and this would have contributed to the appearance of different types of RNA, ribozymes, and ribosomes. In the process of temperature fluctuations of nucleic acids, they would have been able to capture foreign fragments of nucleic acids, along with various polypeptides and proteins. Thus, the primary genomes would have been enlarged, and stabilizing proteins and enzymes would have appeared. Temperature fluctuations would also have caused multiple reversible denaturation of proteins. Renatured protein chains, folding in a different way, could capture various molecules and prosthetic groups, which would determine their evolution and new structural and functional properties. This could have enabled the appearance of thousands of different proteins and enzymes, which would have provided for the formation of all kinds of structures, types of metabolism, and functions. Molecules of amphipolar lipids aggregate in an aqueous medium in the range of temperatures congenial to life to form monolayers, bilayers, and various micelles. These formations would also have changed their structural organization under significant temperature fluctuations, folding in different ways, capturing various molecules and, in the end, forming primary membranes.

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Colloidal coacervates would have liquefied with increasing temperature, becoming disordered and absorbing various substances, micelles, and macromolecules due to diffusion from the environment. After a fall in temperature, the coacervates would have become denser again, re-ordering in a different manner and thus forming compartments with new structures and properties. Temperature fluctuations would have either weakened or strengthened the hydrophobic and hydrophilic forces in the lipid bilayer of biomembranes, thereby facilitating the selective capture and incorporation of various amphipolar lipid molecules, proteins, and enzymes. In this way, various membranes, organelles, and compartments could have formed, differing in structure and function. Such membranes covered the colloidal body of the cell, offering protection for the internal contents and a means of interaction with the external environment. Temperature modification of nucleic acids, proteins, coacervates, and membranes would have occurred simultaneously in a single autonomous liquid aqueous microspace. That is, their mutually influencing coevolution took place. The defining event of the origin of living bodies was the combination into a single whole of a natural nucleoprotein replicator, enzymes, and membrane-covered coacervates (see Fig. 8.2). This co-evolution would have ended with the triumphant emergence of our common ancestor. It would have possessed a relatively stable semi-conserved genome, which began to use the phenotypic framework for its own purposes of survival and interaction with the external environment. Then, special proteins and enzymes, complementary to nucleic acids, would have appeared as a result of temperature coevolution, ensuring replication and amplification even at moderate temperatures. And with the advent of DNA polymerase, a fully-fledged replication mechanism for the primary genome would have appeared, independent of temperature fluctuations. This would have been followed by the emergence of RNA polymerases and ribosomes, which determined the most important processes of transcription, translation, and controlled metabolism. Yet, the development of these last steps is quite astonishing and remains unclear. How could all this have arisen before these final steps? All of these final mechanisms would have been initially and inevitably necessary for the synthesis of all the structural proteins and enzymes, as well as for the implementation of DNA duplication, etc. Even under the most ideal laboratory conditions, such reactions are in no way possible without the presence of the most complex enzymes, and the latter are not self-formed from the primordial broth, but synthesized with the participation of all the most complex mechanisms that must be equally present and perfectly functioning, both in the common ancestor and in its distant descendant. This question still awaits a rational explanation, but the answer will certainly be connected with the inherent natural properties of organic molecules within the range of thermodynamic conditions suitable for life. Thus, it seems that constant temperature fluctuations on our young planet would have been a determining factor in the natural creation of our common ancestor millions of years ago.

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Once again, we emphasize the fundamental importance of the temperature factor, which lies in the fact that life is fixed on the Earth only within the narrowest range of the very low, near-ice temperatures. The lower limit of active life is determined by solid water, while the upper limit is specified by the instability of protein chemical bonds at temperatures above 42–45 °C.

8.4 Properties of Genomes and Evolution The system of life on Earth has been maintained for billions of years, under conditions of constant changes in the geophysical environment, thanks to the continuous adaptation and evolution of its constituent populations and species of individuals. Mortal individuals are not subject to evolution during their short life, but their descendants may have new properties. These properties of new generations are primarily due to genetic modifications of their genomes. That is, the ability of populations, species, and the planetary system of life itself to exist in a sustainable manner is determined by the properties of the genomes of individuals regarding variability, heredity, and evolution.

8.4.1 Heredity Heredity is the property of living bodies to preserve and transmit similar traits over a number of generations, to ensure the specific nature of their own development. Due to heredity, parents and descendants have the same qualitative set of cells, the same biochemical composition of tissues, the same kind of metabolism, and the same functions, morphological features, and many other characteristics. That is, the genotype and standard phenotype for a given species are fully inherited. This is ensured by the fact that virtually the same genome is passed from parents to offspring in each event of reproduction during the entire lifetime of a given species of organisms. The heredity of genomes ensures the permanence and stability of all biological species of living bodies. Heredity does not matter for the process of the life of a separate living body (individual life). Organisms are born and develop into completely standard and unchanging forms. Their lifespan is limited and they cannot do anything about it (Chap. 11). But they can also perfectly well live their lifetime without reproduction, without heredity, and without evolution. That is, the meaning of their existence is not just to exist, but to incubate and multiply genomes that can evolve and repeatedly move to new bodies, replenishing the natural losses of the perishable elements of the planetary system of life. Thus, individuals are simply burdened and tasked by Nature with the duty and ability to reproduce, although this property is completely useless for themselves (Chap. 9). For example, some people can live a perfectly successful life without

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leaving behind offspring, and castrated animals can also successfully live their genetically determined term. But the properties of reproduction and heredity are extremely important for the existence of biological species and for the unified planetary system of life, as they constitute the fundamental basis for maintaining the quantitative and qualitative composition of this system, constantly replenishing it and stabilizing it against the background of gradual evolution. Cell division is the cytogenetic basis for various types of reproduction and heredity. Any type of cell division, and hence heredity, is based on the DNA replication mechanism. The genetic material is doubled and then evenly divided between the daughter cells. The information recorded using the genetic code is passed on to descendants. During sexual reproduction, the transfer of genetic programs for the development of traits is carried out from ancestors to descendants through the genomes of gametes, i.e., eggs and spermatozoa, containing a haploid set of chromosomes. A zygote is formed as a result of fertilization, containing the diploid genome of a new organism. This determines the development of the same phenotype of a new organism through the mechanisms of expression. In asexual reproduction, genetic programs are passed on to subsequent generations simply by dividing cells. Due to heredity, all representatives of the same type of cells or organisms have the same genomes and phenomes; standard genetic programs are realized, and template sets of proteins are synthesized, performing typical reactions, processes, and functions. Hence, each type of organism reproduces its own kind without fundamental changes from generation to generation for millennia. This maintains the species homeostasis of the planetary system of life. Many patterns of inheritance of traits are known to depend on various conditions. For example, on which chromosomes the genes are located, are they allelic or nonallelic, how many genes determine the development of a trait, are they dominant or recessive, linked or not, and so on. However, despite the various complex mechanisms of inheritance, various interactions of genes, crossing over, and complex mechanisms involved in the formation of traits, fundamentally similar individuals are formed in the process of development, possessing the same morphological, physiological, biochemical, and genetic characteristics as their ancestors. And everything is repeated this way, countless times, over many thousands of generations. There is a genetic continuity of life within any species of organisms. That is, genetic information is repeatedly rewritten, transmitted, stored, and reproduced. Then it is rewritten again, stored, transmitted, and reproduced again and again, with practically no changes in the genomes and phenomes, for hundreds of millions of years. Heredity is based on the following properties of genomes: (a) stable genetic code, (b) rather high stability of genes and DNA molecules, and (c) constancy of chromosomes and karyotype within a given species of genome. In addition, heredity is ensured by the highest accuracy in the molecular and cellular mechanisms that ensure the transformation of genetic material and genetic information in the process of reproduction. Thus, the constancy of the existence of particular species of living bodies and the unified system of life on Earth are determined by the phenomenon of heredity. This

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phenomenon is an extremely important property of genomes, as it can (1) transmit the standards of organization and movement of biological matter down a series of millions of generations of cells and organisms, (2) determine the long-term existence of the multitude of species of genomes of living beings, and (3) ensure the stability of the planetary system of life on Earth, as well as its continuity.

8.4.2 Variation Variation is what brings about the emergence of a colossal diversity of living organisms, the mechanisms of their adaptation, and the very basis of the evolution of the planetary system of life. Variation is the property of living bodies to acquire new traits, new variants of traits, and new combinations of traits, or indeed to lose some of them. Variation gives rise to a vast number of traits and their variants, and this is a prerequisite for adaptation and survival, as well as for the variety of cells and living bodies. The main causes of variation are modifications, mutations, recombinations, gene exchange, and symbiosis. If new variants of traits are transmitted to descendants, they are considered to be heritable, or genotypic variations, and otherwise, non-heritable, or phenotypic. 1. Non-heritable (phenotypic) variation is the ability of organisms to change their phenotype under the influence of external and internal environmental factors without transferring these traits to their offspring. This is connected with the property of the genomes of individuals to preserve their structure, nucleotide sequence, and composition of genes or their combinations, even when temporarily living in unusual conditions. That is, only the phenotypic framework (body) actually undergoes modifications, while the genome itself remains unchanged throughout the life of an individual. Phenotypic changes that arise under the influence of factors in the external or internal environment are called modifications. They affect only the traits of the organism itself, not those of its descendants. Modifications are due to the effect of environmental factors on the physicochemical properties of cells, on cytogenetic processes, on metabolism, and on the organization of biosystems, but they have absolutely no direct effect on the structure of the genome, although the genome without a doubt responds to signals from the external environment and participates in the processes of adaptation of its phenotypic framework. At the same time, its structural and informational state does not change, and the resulting gametes do not bear traces of the action of unfavorable factors. Therefore, the next generation will not inherit temporary modifications. In most cases, such modificational variability is a temporal adaptive response aimed at ensuring survival under certain conditions. Phenotypic variability does not result in fixation of the acquired traits in the genomes of either somatic or reproductive cells. Thus, such traits are not passed on to descendants.

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2. Heritable (genotypic) variation is associated with the property of genomes to change their structure, nucleotide sequence, and composition of genes or their combinations, features which can be transmitted to subsequent generations of cells and organisms during reproduction and manifested in them through a variety of phenotypic variants of the trait. The number of chromosomes and the ploidy of the genome may also change. Heritable variation is extremely important, since it serves as the main source of the genotypic and phenotypic diversity of offspring, which is the working material for natural selection and evolution. This type of variation is subdivided into mutational and combinative. Mutational variation. A mutation is a sudden persistent change in the structure of genomic elements, leading to the appearance of new traits or their variants in descendant cells. Mutations can be beneficial, neutral, or harmful. Mutations are a general biological phenomenon, characteristic of all types of living organisms. Mutations in germ cells have no effect on the producers of gametes, but may have a great effect on their offspring. They may result in the appearance of new and beneficial hereditary traits, but they may also lead to abnormalities in the structure of the offspring’s body, impairment of various functions, and even hereditary diseases. In general, mutational variability has tremendous positive significance, since negative traits do not usually pass through the “filter” of natural selection, and beneficial traits determine adaptation and evolution. The process of occurrence of mutations is called mutagenesis, and the factors causing mutations are called mutagens. Mutagenic factors are classified into exomutagens caused by the external environment and endomutagens with internal causes. Endomutagens may include the metabolic products of an organism (for example, toxic forms of oxygen formed in the respiratory electron transport chain). Exomutagens can be subdivided into: (a) physical (ionizing radiation, ultraviolet rays, temperature, etc.); (b) chemical (formalin, mustard gas, colchicine, many resins, salts of heavy metals, some medicinal substances, toxins of bacteria, parasites, etc.); and (c) biological (viruses, viroids, plasmids, episomes, IS-elements). Mutations can also be caused by errors in DNA replication and recombination, as well as defects in the processes of mitosis and meiosis. Organisms or cells that have a mutation are called mutants. Both germ cells and somatic cells can undergo mutations, but only the germ cells can transmit modifications of their genome to descendants. Depending on the type of changes in the genome of cells, there can be genomic, chromosomal, or gene mutations. Genomic mutations are due to a change in the number of chromosomes in the karyotype. These include polyploidy and heteroploidy. Polyploidy is an increase in the number of chromosomes by 2, 3, 4, etc., times as a result of the addition of complete chromosome sets due to violations in division during reproduction. Heteroploidy refers to the situation where the number of chromosomes in gametes changes due to violations in the complex molecular processes of meiosis. Involvement of such gametes in fertilization results in the formation of abnormal zygotes. If any of the chromosomes in the karyotype of an organism appear in a triple set, then this is

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called trisomy (2n + 1). For example, Down syndrome in humans is the trisomy on chromosome 21 (47, + 21). Chromosomal mutations are associated with changes in the structure of chromosomes. They are also called chromosomal rearrangements, or chromosomal aberrations. Disruption of the chromosome structure is a consequence of a violation in the processes of crossing over, meiosis, or mitosis, as well as the action of other factors leading to the formation of chromosome fragments. Such fragments can be reunited, but without restoring the normal organization. Chromosomal rearrangements lead to a change in the morphology of chromosomes, which is noticeable even under a light microscope. Rearrangements of the chromosomes of germ cells change the genetic balance, as well as the genetic programs for the development and functioning of the embryo. The nature of the interaction of genes and their expression changes. This negatively affects the structure and function of cells and organs and leads to serious consequences. Mutations often turn out to be incompatible with the development of a new organism or cause the appearance of pathologies. However, some chromosome rearrangements can be beneficial for evolution. For example, humans have 23 pairs of chromosomes, while modern apes have 24 pairs. It is assumed that a significant emergent stage in human evolution was the “fusion” of the 12th and 13th chromosomes of monkeys and the formation of the 2nd human chromosome, which almost completely corresponds in genetic composition to its predecessors. As a result, there was a change in the number of pairs of chromosomes and combinations of genes, which was probably one of the reasons for the appearance of humans. Gene mutations are associated with a violation in the structure of one gene. In this case, the changes are usually associated with only one or a few atoms of one or a few nucleotides. Therefore, such mutations are also called point mutations. This causes a change in the order when reading the information from the genetic code, and this leads to a change in the amino acid sequence of the synthesized proteins or to the termination of the synthesis processes altogether. The result is the appearance of a defective protein or the absence of an enzyme, which disrupts cellular metabolism, differentiation, and development, and causes the emergence of new traits in the offspring (including pathologies). Mutational changes in the genomes of the sex cells of an individual do not have any consequences for that individual (the producer of the gametes), but have a great influence on the properties of its offspring, as well as on the genotype and phenotype of the population, whence they provide evolution with material for natural selection. Somatic mutations. Different types of mutations (gene, chromosomal, or genomic) can also occur in the somatic cells of living organisms. Somatic mutations can be caused by physical, chemical, or biological factors. They can result in the appearance of new traits of cells, tissues, or organs in a given living body. Such changes in the genome are not inherited by the descendants of this organism, but are inherited only by the descendants of these somatic cells within this particular organism. That is, they do not entail changes in the genotype of subsequent generations of individuals, since they are not inherited, being a case of non-heritable variation. However, for the descendants of this mutant cell, the variability is hereditary, since subsequent

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generations of cells within this particular organism will inherit and further clone the mutation. In some cases, this can have adverse consequences. For example, a group of cancer cells may appear in a multicellular organism, as a result of a change in the structure of the genome of individual cells, possessing genetic defects in the regulation of cell reproduction and the ability to divide without limit. This has tragic consequences for the individual, but fortunately it is not inherited by its descendants. There is a randomness and unpredictability in both the mutations themselves and their consequences, and hence the entire process of genome variability. A vast number of different physical, chemical, and biological factors can act on different chromosomes, on different parts of chromosomes, and on different segments and nucleotides of DNA. Recombinations can also affect any segment of any DNA. Most of the constantly emerging mutations are corrected by genome enzymes, but some still manage to appear. This leads to the appearance of various phenotypes with unpredictable traits and their combinations. Of these, only a few get through the “filter” of natural selection. As a result, for many hundreds of millions of years of evolution, there have been and still are many different cells and organisms that have passed the test of natural selection and adapted to certain conditions. But many more random genotypes and phenotypes of cells and organisms have been eliminated by natural selection. In all the cases described above, mutations are associated with the action of various endogenous and exogenous factors on a rather flexible genome. That is, the genome possesses the property of variability, even though at the same time it has the means of protection against violations and the tools for repair. Combinative variability appeared with the advent of sexual reproduction. This type of heritable variation arises from variants in the recombination of parental genes and alleles and is the source of an infinite diversity of combinations of traits in the resulting offspring. Therefore, there are no people or other animals who are absolutely identical in all their hundreds of traits, and there never have been. Combinative variability in mammals is determined by the following processes: (a) countless options for meeting sexual partners who have different variants of allelic composition in their genomes; (b) countless variants for fertilization of different egg cells with different sperm cells, and since all haploid gametes have a unique allele composition, each diploid zygote will have a unique combination of genes; (c) recombination of alleles during crossing over and the formation of new gene linkage groups in gametes; (d) independent and random divergence of chromosomes during meiosis; (e) different variants of the combination and divergence of parental chromosomes during the first division of a zygote. In humans, the minimum number of possible variants of gametes, both in men and women, is approximately 223 (excluding crossing over). And the number of genes in a human is around 25,000. Hence, the number of possible variants of the genotypes of descendants is nearly infinite. A change in allele combinations leads to the appearance of organisms with other genotype variants, which causes changes in the phenotype. For example, children of the same parents always differ in a number of traits, sometimes very significantly from each other and from their parents, due only to combinative variability.

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An example of combinative variability in humans is the formation of phenotypes of blood groups of the ABO system: if the mother is heterozygous for the second A (II) blood group and the father is heterozygous for the third B (III), then their children may have the first O (I) and fourth AB (IV) blood groups that their parents did not have. Combinative variability provides material for natural selection and evolution, playing an important role in the emergence of new populations. This can be exploited by humans. Many varieties of agricultural plants and breeds of domestic animals have been created by humans through hybridization of pre-existing breeds. Combinative variability is of great importance for adaptation and evolution, and also has a certain value in speciation. In all cases, the variation in the phenomes of offspring is based on the combinative variability of their genomes. Thus, the genotypic and phenotypic diversity of cells and organisms and the appearance of various favorable or unfavorable properties and traits, while maintaining the fundamental characteristics of the species, is based on the phenomenon of heritable variation. This allows the descendants of organisms, on the one hand, to inherit all the main structural and functional characteristics of their biological species, and on the other hand, to adapt to changing environmental factors. It should be noted that variation at the genome level which does not lead to death or serious pathologies is associated only with its allelic or molecular modifications with maximum preservation of the karyotype. Changes in the number of chromosomes or damage to them often lead to loss of viability. Usually, natural selection already destroys such individuals and their genomes at the embryonic stage or in the early stages of development, preventing them from reaching sexual maturity and reproducing. This supports important hereditarily fixed traits of the species. Only those modified organisms that not only carry some new useful traits, but also retain the entire range of the main traits of the species pass through the “filter” of species selection. That is, heredity and variation act together during the reproduction of a biological species. Heredity preserves the main traits of representatives of biological species unchanged, whereas variation provides slightly modified material for natural selection. Thus, it is heritable variation that is the strategic survival mechanism of biological populations and species (Chap. 12), determining their evolution. It is the heritable variation of genomes that ensures that biological species overcome the pressure of entropy through the evolution of their descendants. It is heritable variation that maintains the permanence of such a diverse planetary system of life under the conditions of the evolving Earth.

8.4.3 Natural Selection Natural selection is a process of nature acting at the level of species and populations, as a result of which the number of individuals in a given taxon with a greater adaptability to environmental conditions increases, while the number of individuals

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with unfavorable traits decreases. Natural selection is one of the main mechanisms of evolution. A large number of phenotypically different cells and organisms with equally diverse genomes live in various ecological niches. The level of adaptivity of the possessors of certain phenomes (and hence of genomes) is different. Selection of the best adapted organisms is directed toward choosing and consolidating phenotypic traits in the population that increase the chances of survival. Since any traits are determined by certain genes, alleles, and their combinations, natural selection of phenotypic traits actually picks out those genomes specific to the best adapted organisms. That is, natural selection has a molecular genetic basis. Its result is not only the survival of the fittest organisms, but also the enrichment of the gene pool of a population with useful genes. The emergence of almost unlimited material for selection occurs as a result of continuous reproduction, which is based on the phenomenon of copying and cloning of nucleic acids. The emerging individuals have a variety of genotypes and phenotypes due to the mechanisms of heritable variation: mutations, combinative variability, hybridization, and gene exchange. As a result of these processes, numerous individuals with new genes and traits appear in populations, along with all kinds of combinations of them. Natural selection also acts as a factor of stabilization of populations and species. It does not allow the fixation of sick, weak, and maladapted individuals in a population. Selection occurs at all stages in the ontogeny of organisms. For example, in mammals, at the pre-embryonic stage of development, environmental conditions select only the most complete and active spermatozoa out of millions in the process of insemination and in the early stages of fertilization. At the stage of embryonic development, the predominant selection mechanism is selective mortality. Further, malformed, abnormal embryos carrying modified genomes, containing gene, chromosomal, or genomic mutations, are eliminated from the population. A large number of weak organisms also die immediately after birth. Selective death occurs with the organisms possessing various structural and functional defects, most of which are caused by defects in the genotype. Surviving, but defective organisms, if they even reach the reproductive age, are much less likely to leave behind any offspring, and are therefore much less likely to pass on their defective genes. As a result, natural selection ensures selective reproduction of genomes. For this reason, favorable traits, and hence their genes, accumulate in a number of generations and gradually change the genetic composition of the population in a biologically expedient direction of adaptation and distribution. In nature, such selection occurs through environmental factors and exclusively according to phenotypic characteristics. That is, there is a selection of genomes through the selection of their best adapted phenotypic frameworks. As an evolutionary mechanism, natural selection operates on populations. In this case, the objects of selection are individuals that appear as a result of reproduction. Selection is based on the presence of new traits or the lack of old ones. This leads to selection of specific genes, alleles, or combinations thereof. This brings about change in the qualitative and quantitative composition of the population gene pool.

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This is the main prerequisite for the emergence of better adapted individuals and the emergence of new populations of organisms with even more perfect genomes. Selection can occur under the influence of any factor that changes genotypes in such a way that increases their chances in the struggle for existence and increases the likelihood of reproduction of specific individuals with certain genes and their combinations. Consequently, the basis of evolution is the change in gene frequencies in the aggregate genome of a given population from one generation to the next. Thus, natural selection is a mechanism of selection of genomes that leaves only the viable variants of living bodies. Genetic traits beneficial to organisms that have undergone a selection process are called adaptations. Various adaptations increase the survival rate and probability of reproduction for the organisms in their habitat. Thus, the real effect of natural selection is to increase the frequencies of those genes and DNA molecules in the population that ensure the success of reproduction and survival of their possessor. Indeed, regardless of the complexity of their structure, all living organisms that have passed the selection process are expediently constructed and perfectly adapted to their natural environment. Even the most primitive organism necessarily possesses the minimum set of essential functions required for survival. Consequently, any successfully existing genome is perfect in relation to the phenome it defines, and this in turn fits its habitat almost ideally. Hence, natural selection, as a tool of evolution, has led to the emergence of an enormous variety of genomes and their phenomes, which have survived and adapted well to their habitat. This has provided a comprehensive distribution of living bodies throughout all ecological niches on our planet and contributed to the formation of a single planetary system of life.

8.4.4 Evolution Gradual changes occur constantly in both living and inanimate nature. In particular, mountains are destroyed, river beds change, ravines are formed, lakes dry up—the surface of the Earth is gradually transformed. This also leads to a change in the climate and conditions for the existence of living organisms. Thus, the process of adaptation and evolution of living bodies is predetermined by gradual changes in the physical and ecological conditions on Earth, which in turn are associated with the global processes of the Solar System. Under such conditions, only those organisms that have properties that contribute to adaptation and survival can multiply and spread. After several generations, organisms with this phenotype will already dominate in this population as a result of natural selection of the fittest. In this way, over centuries and thousands of generations, the evolution of living bodies gradually moves on. Biological evolution is a continuous gradual development of living nature, accompanied by modifications of organisms in accordance with changes in environmental factors and internal needs in order to adapt and survive. It occurs on the basis of the heritable variation of genomes of living bodies, their natural selection, and changes

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in the genetic composition of populations. The result is the formation of adaptations of living bodies, speciation, transformation of ecosystems, and the planetary system of life. Darwin’s theory of evolution, created in the middle of the nineteenth century, convincingly explains the diversity, the source, and the mechanism of the emergence and development of biological species of living bodies. It is divergent in nature, and hereditary variability, natural selection, and isolation were recognized as the main causes of evolution. However, the cellular and molecular mechanisms of evolution were not understood at that time. In the middle of the twentieth century, the theory was refined and expanded due to the achievements of genetics and molecular biology. The modern concept is called the synthetic theory of evolution (STE). It presents the evolution of organisms through natural selection of useful genetically determined traits that occurs in populations. The objects of selection are specific bodies, carriers of the genomes that created them. From this point of view, the evolution process looks like this. As a result of mutations, for example, various changes occur at the level of genes, chromosomes, or genomes. This leads to modification of genetic programs in living bodies, synthesis of altered proteins, changes in metabolism, and so on, and these determine the development of new traits. If these traits increase survival and adaptability under the given conditions, they are more likely to be transmitted through new genomic variants to subsequent generations. The survival and reproduction of the possessors of useless traits and their alleles is less likely. Thus, in a natural way, through the mechanism of selection of phenotypes, useful genes and genomes are selected and new genetic networks are built, which determines the evolution of organisms, the formation of adaptations, and speciation. The main operating factors of evolution are the following processes: (a) mutations, (b) recombinations, (c) crossing and hybridization, (d) gene exchange, (e) symbiosis, and (f) directed genome rearrangements (see Sect. 13.10). Despite the rather high stability of genotypes and the presence of reparative processes, DNA molecules, chromosomes, and karyotypes undergo modifications from time to time, and these cause changes in the complex genetic apparatus. The consequences of these changes materialize and multiply in the processes of protein synthesis, cell division, and differentiation. This in turn entails the appearance of conditioned traits and their various combinations, that is, new variants of phenomes. It is exactly at this stage that the natural selection of organisms that are favorable for the given conditions occurs depending on the phenotype. Such individuals survive and leave behind offspring, which ensures the consolidation of useful traits in the population. Consequently, it should be emphasized once again, the selection of the corresponding genomes actually occurs according to their phenotypic framework. One of the postulates of STE is that the object of evolution is the population, where the frequency of a specific gene, which determines a new trait, gradually changes. An individual cannot evolve and acquire new characteristics, since it has a finished form and lives only for a limited time. Whereas in a population, in the process of change of generations, individuals with useful mutations can gradually accumulate, new combinations of genes can be

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created, and the genome can change. As a result, more and more individuals appear with new traits, which they pass on to future generations. The evolution of a particular population can lead to the emergence of a new species, or, one might say, a new species of genome. It follows from this that the specific place of application of evolution is not the population’s phenome, but its aggregate genome. It is the genome, which undergoes primary modifications that lead to changes in its phenotypic frameworks. So, the evolution of living bodies and their genomes is provided by three fundamental phenomena: variation, heredity, and natural selection. Variability, based on the plasticity of the genetic material, creates a lot of variants and ways of developing a particular biological system; heredity, due to the conservatism of the genome, does not allow the system to go beyond the genetic framework of the population; and selection, in accordance with environmental conditions, fixes a limited number of adapted forms. Looking at evolution in retrospect, it is clear that as we go down the evolutionary ladder, we are getting closer and closer to the essence of life. From multicellular to unicellular, from eukaryotes to prokaryotes, from prokaryotes to viruses. As a result, the “naked truth of life” is a minimal complex, represented by a DNA (or RNA) molecule and several proteins. The interacting combinations of these molecules determined the emergence of qualitatively new systems—cells and living bodies. Interestingly, the basic molecular processes and mechanisms that determine life have hardly evolved. In modern multicellular organisms, including humans, the key life processes, i.e., replication, transcription, and translation, have remained unchanged. Also unchanged are the enzymes that serve these mechanisms. They are nearly identical to the mechanisms found in bacteria and archaea, some of which have lived for more than three billion years. Hence, a significant number of major evolutionary accomplishments testify to progress in the development of life. Having arisen in the simplest forms, in its process of development, life naturally gave rise to organisms with an increasingly complex type of structural organization, more perfect functions, a high level of adaptation, and independence from environmental influences. New variants of species of living organisms that have arisen on Earth do not last forever; they live as long as there are environmental conditions that satisfy their vital needs. Consequently, the evolution of organisms at any stage is adaptive and temporary. Evolutionary processes in biological systems are mostly probabilistic in nature. DNA has appeared and is now a factor capable of exerting a dramatic influence on the structuring of the chaotic surrounding material space. But the DNA molecule itself also appeared as one of the many variants of chemical evolution and is subject to various influences, acquiring probabilistic mutations, which are in turn selected by environmental conditions. That is, the emergence of various traits and living organisms was determined by the random actions of certain environmental factors on nucleic acids. Consequently, millions of species of organisms living on Earth have random genomes and phenomes. Moreover, both now and later, they will evolve in the same unpredictable manner. And with a possible repetition of the evolution of living organisms, the process will proceed in a completely different, absolutely unpredictable way. This means that any species of living organisms is unique, and

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once it disappears from the face of the Earth, will never reappear again. The same applies to any individual. It is believed that the emerging species of living organisms can exist and gradually evolve for quite a long time, on average 2–10 million years. Afterwards, they disappear or become modified. It is assumed that changes in the environment or mutations cause rapid changes in the gene pool on an evolutionary time scale, and within several thousand years, the species disappears. Probably, trilobites, ancient fish, dinosaurs, giant birds, mammoths, and other large species, classes, and types of animals died out suddenly in this manner. Consequently, it can be considered that the evolution of life on Earth consists not only of slow processes of adaptation and modification of species, but also the saltatory rapid destruction of old genomes and gene funds and the creation of new ones. But most likely, both gradual and saltatory mechanisms of disappearance and appearance of new biological species take place in the global process of evolution. The synthetic theory of evolution regards the genome as a passive structure that encodes and transmits randomly occurring variations of genotypes that are constantly sifted by selection. According to this point of view, only selection plays an active role, transforming random genotypic modifications into necessary traits, while the genome passively follows selection. However, in recent years, more and more experimental facts have appeared, indicating the possibility of purposeful targeted modifications of the genome, which do not just determine development and evolution in a random and accidental manner. In recent years, more and more facts have become known indicating that the genome is an active self-regulating and self-organizing system (see Sect. 13.10). At the end of the last century, Barbara McClintock suggested that “the genome is a highly sensitive organ of the cell, which, during stress, can initiate its own restructuring and reconstruction.” Modern scientific data confirm that the most successful gene from an evolutionary point of view is the one that is able to change directionally if necessary. This means that there are mechanisms in the genome that control and create a variety of coordinated DNA rearrangements. It is assumed that the mechanisms of an adequate response of the genome to environmental factors could arise and evolve in the same way as any other function of the cell. The evolution of the planetary system of life can be judged by the appearance over billions of years of more and more complex forms of living bodies and their phenotypic frameworks. Moreover, the interrelated changes that we see in the aggregate of phenotypes of living bodies are, in the end, only a consequence of the co-evolution of discrete genomes within the unified system of the global genome. The general scheme of biological evolution is complemented by scientific, technical, and cultural evolution associated only with humans. The application of the scientific method in the life of society, the use of scientific achievements, for example, the spread of computer technology, manipulations with genetic information, etc., are part of this evolution. The process of social evolution is associated with the transfer of cultural and scientific information from generation to generation in a non-genetic way. This type of social information also evolves and passes through the “filter” of natural and artificial selection according to the criterion of usefulness for individuals and society. Social information is deliberately created by humans and has a specific

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purpose. That is, given the rather strong influence of our species on the world around us, we can say that humanity has become a new and powerful factor in the evolution of both living and inanimate nature. It should be noted that biological evolution is based on the phenomena of death and reproduction of living bodies. It is death that naturally eliminates biological material that is outdated or bears unfavorable traits, and hence makes natural selection possible. It is reproduction that provides a variety of new material for evolution. At the same time, variation creates a mass of options and ways for a particular biological system to develop, while heredity retains the basis of the original genotype, narrowing down the number of new variants, and natural selection weeds out non-conforming organisms, in accordance with environmental conditions and fixes a limit on the number of adapted forms. Thus, the existence and development of life as a natural phenomenon is associated with constant evolution. Moreover, it is likely that evolution is not necessarily due only to changes in conditions of existence and adaptation. This process can probably also be determined by the internal motives of the genome. Evolution is inevitable and uninterrupted due to the fact that the created adaptations of organisms are not universal in time, and as a result are overcome by the pressure of entropy. New types of living organisms appear, live, progress, and in the end, become modified into forms better adapted to their changing environment, or disappear as a result of their inability to survive under new conditions, or get replaced by stronger species. It follows from this that humans will not be eternal on Earth either. It is likely that in thousands or millions of years this species of mammal will be unpredictably modified or perhaps even disappear, since it is difficult to predict or even imagine what changes will occur in its genome, nor what the environmental conditions will be, nor what competitive species may appear. However, it should be emphasized once again that it is precisely the property of genomes to evolve that ensures the adaptation of living bodies, the survival of populations and species, and the preservation and progress of the phenomenon of life on our changeable planet over billions of years. According to the second law of thermodynamics, our universe is dying. The strategy for the development of life on Earth can in turn be put down to the evolution of the Solar System, unpromising as it may be for us. Only those who change can survive. That is, the cause of evolution is entropy. Evolution is unavoidable. Evolution or death! And there is one more, dialectical argument. From the point of view of Her Majesty Nature, one should not attach such great importance to the phenomenon of life. This is just one of the myriad manifestations of the properties of our boundless Universe. There is nothing constant in space and time, and this includes all living beings. Only change remains unchanging.

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8.4.5 Co-evolution The surprisingly expedient organization of the planetary system of life and the interconnection and interdependence of various species of organisms is explained by the process of their long-term cumulative interdependent co-evolution. This means that the totality of living bodies and their systems have simultaneously and interdependently changed over billions of years as a single whole, as a unified system of life, gradually creating, selecting, and building together common processes, structures, and mechanisms. For example, we assume that it is only as a result of molecular co-evolution that structurally and functionally interconnected DNA, RNA, and the language of the genetic code could eventually appear, along with the processes and mechanisms of transcription and translation, as well as a unique set of molecular robots— protein enzymes performing specialized highly skilled work. The ideal adaptation of various organisms to each other and their interdependence is also explained by the phenomenon of co-evolution. These are the processes of cumulative interdependent mutual adaptation of organisms to certain ecological niches, processes which have been going on for millions of years and generations. This explains, for example, the existence of strict food chains, when the loss of just one link can lead to the death or reduction in the number of individuals in different populations. It is also the mutual adaptability of insects to feeding and of plants to pollination. It is also the phenomenon of complete dependence of a particular parasite on the host, which is a consequence of their joint evolution. It is the absolute dependence of herbivorous animals on the presence of certain types of plants and much more. Plants, animals, bacteria, and other organisms evolved simultaneously and interdependently, as components of a single planetary system of life, or one might say, of a single organism. That is, no population within a particular ecosystem evolves independently of all the others, but only in interaction with others and the environment. This means that it is better to talk not about the evolution of this or that organism or population, but rather to talk about co-evolution as a global phenomenon of nature. That is, the evolving genomes and phenomes of organisms must adapt not only to environmental factors, but also to the genomes and phenomena of the surrounding bodies. Thus, the organisms of the planetary system of life have acted and are still acting as yet another mechanism of natural selection.

8.4.6 Symbiogenesis Another reason for the variability and evolution of living bodies is symbiosis. This is a well-known form of close relationship between organisms of different biological species, beneficial for at least one of the participants.

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In the middle of the twentieth century, Lynn Margulis published a hypothesis taking this into account, and over the following years developed it into a theory now known as symbiogenesis. It states that long-term forms of symbiosis have led to the emergence of new properties and forms of life. According to this theory, the creation of new life forms through symbiotic relationships is considered to be one of the driving forces of evolution. The most convincing evidence of evolution through symbiosis is provided by the organelles of eukaryotic cells—mitochondria and chloroplasts. They contain their own genetic material corresponding to bacterial and reproduce on their own, independently of the rest of the cell. This indicates that these organelles were originally free-living bacteria, which in ancient times invaded other microorganisms and began to coexist with them, forming a fundamentally new organism (Fig. 8.3). The appearance of a nucleus and a complex genome in cells is also associated with the unification of the cell’s own genetic material with the genetic material of symbionts. Unicellular eukaryotes acquired the ability for voluntary movement as a result of symbiosis with motile bacteria. Thus, symbiogenesis was an emergent factor in biological evolution. As a result, chromosomes of different microorganisms could unite and fundamentally

Fig. 8.3 Scheme of possible paths of evolution based on symbiogenesis. Eukaryotic cells most likely developed as a result of long-term symbiosis—the constant coexistence of various bacteria and other microorganisms. With a complex genome and mobility, possessing two efficient ways of generating energy, symbiotic life forms migrated to different habitats, evolving into precursors of plants, fungi, and animals

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new genomes were produced, bringing into existence the fundamentally different kingdoms of life.

8.4.7 Gene Exchange Gene exchange is the transfer of genetic material between organisms. This process promotes reproduction, as well as the acquisition of new qualities by genomes and evolution. Vertical transfer is observed during asexual and sexual reproduction. This is the transposition of genetic information from a cell or multicellular organism to their offspring using conventional cytogenetic mechanisms. First, the genetic material is duplicated (replication), and then it is transferred to its daughter organisms. The cytogenetic mechanisms of vertical transport are detailed in Chap. 9. Horizontal transfer occurs during the transposition of genetic material from an organism of one biological species to an organism of another species. Prokaryotes. The horizontal movement of genes is quite common among prokaryotes. Several methods of genetic exchange are inherent in them. Conjugation is the purposeful transfer of DNA from one organism to another. In this case, two bacteria are connected with special protein tubes, or conjugation pili, and the donor bacterium transfers part of its genome to the recipient bacterium. Transduction is the transfer of genes as a part of viruses, plasmids, and mobile genetic elements. For example, viruses, passing from one bacterium to another, can take pieces of the bacterial genome with them. Transformation is the capture of foreign DNA from the external environment by a cell. Sometimes bacteria can simply absorb fragments of DNA from the environment and, under certain conditions, integrate them into their own genome. This method of interspecies genetic exchange could play an important role in the formation of a eukaryotic cell. In addition, there is a method for gene transfer in symbiotic systems when cells are in physical contact. If a bacterium inserts a piece of a foreign genome into its circular chromosome, then it changes its properties, that is, it actually turns into another organism. Moreover, its new properties can be passed on to its offspring. In some cases, it is even possible to completely replace the bacterium’s own genome with a foreign genome, that is, it actually changes its species affiliation. With the discovery of horizontal gene transfer, the biological evolution of prokaryotes appears in a slightly different perspective. It turns out that the “successful inventions” of some species of organisms can in principle be borrowed by others. In this case, the planetary system of life appears as a single environment in which prokaryotes, as well as viruses and various mobile genetic elements, spread genetic information (see Sect. 1.14). It can be used just about anywhere in the prokaryotic system, which can be seen than as a single, huge, and incredibly polymorphic species. That is, horizontal gene exchange leads to the genetic integration of prokaryotes.

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But horizontal gene exchange is not at all uncontrolled and unrestricted and usually occurs between related groups. Most often, genes associated with metabolism, transport pathways, and signaling are involved in horizontal transfer. There is evidence that at least 80% of genes in each prokaryotic genome were involved in the processes of horizontal exchange at one stage of evolution or another, hundreds of millions of years ago. Modern genetic engineering is based on the principles of natural horizontal gene transfer. Indeed, for example, bacteria capable of conjugation are true natural genetic engineers. Moreover, they can introduce their DNA not only into the cells of other prokaryotes, but also into eukaryotic cells. A large group of viruses is used by scientists for the genetic modification of a number of eukaryotic cells for experimental purposes. Eukaryotes. Horizontal transfer also occurs among eukaryotes. To maintain their individuality and protect themselves from the introduction of foreign genes, but at the same time preserve their ability to adapt and evolve, eukaryotes have developed complex adaptations. The most important of these are sexual reproduction and reproductive isolation of species. This is what led to the formation of a new type of biological system—endogamous species. However, interspecies reproductive isolation in eukaryotes is still not absolute. In particular, eukaryotes are also capable of borrowing foreign genes. For example, there are cases of horizontal transfer of mitochondrial genes from one plant to another. Fragments of the genome of the Wolbachia bacterium were found in the genomes of 4 species of insects and 4 species of the round worms filaria. And the complete bacterial genome has been inserted into the genome of the Drosophila ananassae fruit fly. That is, the nuclei of the cells of these flies contain two genomes of two different organisms at once. Therefore, the incorporation of bacterial DNA may be one way of acquiring new genes in animal evolution as well. It has been established that genes borrowed from viruses, transposons, and retrotransposons play an important role in the evolution of eukaryotes. These cases can also be considered as examples of horizontal transfer, because organisms in this case receive new genes “from the outside”, from completely different phylogenetic lineages. DNA fragments of viruses and transposons are often “tamed” by higher organisms and begin to perform useful functions in the genome. This phenomenon is so widespread that a special term has even been proposed for it, namely, “molecular domestication”. Thus, for the first time, it has been possible to show that the emergence of evolutionary innovations based on mobile elements is not an exception, but a rule. In fact, there is a constant process and transformation of the so-called “junk” or “selfish” DNA “into useful elements of the genome”. The sexual process can also be considered, not only as an attribute of vertical transfer during sexual reproduction, but also a kind of horizontal gene transfer, since formally, in the zygote during fertilization, the genes of two different organisms are combined in one genome. In both cases, we are talking about interorganismic genetic recombination. And before that, there is a crossing over of chromosomes, during which there is a horizontal movement of alleles.

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Horizontal exchange actually turns the phenosphere into a single “laboratory” for the invention of further useful hereditary traits. Yet, the efficiency of this planetary system of life decreases sharply as the complexity of organisms grows, since multicellular organisms have developed effective, although not absolute, means of protection against unwonted horizontal transfer. Deciphering the genomes of prokaryotes and eukaryotes has shown that traditional concepts of phylogeny, based on the idea of divergence, are insufficient for understanding the genealogy of species. The branching of such trees according to the bifurcation scheme reflects only the principle of vertical evolution (Fig. 8.4). Genomic data suggest that, in the course of evolution, gene transfers have taken place both within kingdoms and between them. It is assumed that, at the earliest stages of the evolution of living bodies, there was a certain shared gene “commune”. The picture of evolutionary relationships in the world of ancestral prokaryotes was not so much a tree as a kind of mycelium with an entangled network of horizontal transfers in the most diverse and unexpected directions (Fig. 8.5). The eukaryotic nuclear genome was also chimeric from the start. It contains a mixture of genes of archaeal and bacterial origin, which combined in the early stages of the formation and evolution of eukaryotic cells. It is also known that most of the genes of the ancestors of mitochondria, viz., alphaproteobacteria and the ancestors Fig. 8.4 Darwinian divergence scheme. The directions of evolution diverge, never connecting again. However, this view of phylogeny is insufficient for understanding the genealogy of species

Fig. 8.5 Diagram of evolutionary relationships in the living world. Here we have a network of intertwining vertical and horizontal gene transfer pathways

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of plastids—cyanobacteria—were transferred into the genome during the process of symbiogenesis. Thus, both horizontal and vertical gene exchange have played, and still play, an important role in biological evolution.

8.4.8 Bioinfogenesis and Infobiogenesis We propose two more possible mechanisms of interrelated sequential processes of generation and transformation of information and living matter, which can provide the basis for the patterns of development and evolution of biosystems, and which can be an integral property of living bodies, one of the main criteria of life. Bioinfogenesis is the process of generating new information in genomes during the ontogenesis and reproduction of living bodies (Fig. 8.6). In particular, new alleles and gene combinations are constantly being formed during sexual reproduction (Chap. 9). This is determined by several cytogenetic processes, such as crossing over during meiosis at the stage of gamete formation. This is also facilitated by numerous combinations when the genomes of the father and mother combine, as well as by numerous variants of the divergence of chromosomes in the anaphase of meiosis. In this way modified genomes appear, containing new genes and alleles, along with their combinations and systems. Such properties of the genetic reproductive apparatus are widely used by breeders to develop new breeds of animals and plants. Dozens of breeds of cats, dogs, chickens, and many other organisms have been created on the basis of crossing, containing different allelic combinations of genes. Thus, during sexual reproduction, there is a constant shuffling and recombination of genes, which leads to countless allelic combinations in nascent organisms. Induced or spontaneous mutations of the genome are possible in the cells of living bodies throughout the process of ontogenesis. Mutation constitutes a highly important mechanism for generating information in the genomes of germline cells. It leads to a variety of modifications of both individual genes and chromosomes, as well as karyotypes. This results in the emergence of new properties and traits in the offspring. As a result of natural selection of daughter organisms, exactly that information which contributes to survival and adaptation is fixed in their modified genomes. So, although bioinfogenesis is a property of living bodies, it does not serve them, but rather the biological species to which they belong. Hence, the formation, accumulation, and shuffling of genetic information occurs on the basis of reproduction, ontogenesis, and generational change. Therefore, during the long-term existence of a biological species, bioinfogenesis leads to the appearance of modified genomes. They gradually change their phenotypic framework in the process of infobiogenesis, which leads to the appearance of modified phenomes. Variants with useful traits get through natural selection, which ensures evolution and the emergence of new populations.

Fig. 8.6 Scheme of transformation and circulation of bioinformation in the processes of ontogenesis, reproduction, and evolution of living bodies. Interdependent cyclic processes of bioinfogenesis and infobiogenesis are mechanisms of the global process of transformation and the emergence of biological information within the planetary system of life. Modification of genomes is a consequence of bioinfogenesis, that is, the appearance of new genetic information. The use of information from modified genomes, or infobiogenesis, creates new variants of phenomes through development and selection, which ensures the process of evolution

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Infobiogenesis is the process of implementing genetic information into the formation and development of living bodies (see Fig. 8.6). Information is used according to the classical scheme: DNA → RNA → protein, using the mechanisms of replication, transcription, translation, and expression. An organism is gradually formed in the process of phased expression of the genome, possessing a set of individual properties and functions. Natural selection fixes variants of phenomes adequate to the external environment, thereby ensuring the fixation of the corresponding beneficial changes in the genomes of the evolving living bodies. The above processes of circulation of information and matter go exclusively through organisms. Consequently, in the context of the above, living bodies can be considered as sites and means of conjugation of special information and material flows. Hence, bioinfogenesis and infobiogenesis are two closely related components of the general cyclic process of generation and transformation of information and living matter, on which the patterns of development and evolution of biosystems are based. Functioning together and complementing each other, such cycles of transformation of biological information and living bodies fully ensure the versatile manifestations of life and its adaptation, evolution, and survival. That is, the ability of living bodies to independently generate (bioinfogenesis) and use (infobiogenesis) information is the basis for the existence and evolution of the planetary system of life.

8.5 Summary Life in the form of an autonomous cell arose from inanimate nature on the basis of its laws, through chemical evolution due to spontaneous aggregation, interactions, and the gradual complication of molecules under the conditions then prevailing on Earth. The likelihood of this path of origin is extremely low, but does not contradict the laws of nature. An organizationally fundamentally new, stable molecular system, viz., a cell, a living body with its own individual life, was created 3.5 billion years ago. The following billions of years did not make any fundamental changes and additions. That is, once created, the first example of cell organization was copied and cloned together with DNA over many millions of years in the process of reproduction. Evolution has built a huge number of types of living bodies, using variants of the qualitative and quantitative composition of molecules and cells. But they are all descendants of the model of organization and mechanisms that were created by nature billions of years ago. Thus, the pattern of organization of living bodies is manifested by a structural and functional combination of genome and phenome, the main properties of which are the ability to carry out autopoiesis and reproduce. The emergence of prokaryotic cells was a qualitative leap in the evolution of matter, since this made it possible to create a highly ordered system with fundamentally new properties: metabolism, energy conversion, autopoiesis, and reproduction. Then, on this basis, a more complex variety of eukaryotic cells arose. Their combination and specialization in structure and function ensured the origin of multicellular

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organisms, and ensured further evolution. As a result, the planetary system of life came into being, uniting all living bodies and genomes into a single network. The continuity of life on Earth is due to the phenomenon of heredity. This phenomenon is extremely important, as it ensures survival in changing conditions and transfers the standards of organization and movement of biological matter in a series of millions of generations of cells, enabling the long-term existence of various species of living beings, as well as the continuity of the phenomenon of life on Earth. The phenomenon of variation becomes the basis of adaptation and evolution, as well as the cause of the colossal diversity of living organisms. Natural selection determines the fixation of the genomes and their phenomes, which have survived and adapted well to their habitat. Evolution is inevitable and uninterrupted due to the fact that the created adaptations of organisms are imperfect in time and, as a result, are defeated by the pressure of entropy. This means that it is precisely the overcoming of entropy through evolution that ensures the adaptation and survival of living bodies on our ever-changing planet for billions of years. Having a single physical and informational nature, genes can be transferred, incorporated, exist, and be expressed in “foreign” genomes. The evolution of phenomes proceeds on the basis of bioinfogenesis—the appearance of new genetic information in their genomes during ontogenesis. And in its turn, the use of this information, referred to as infobiogenesis, determines the emergence of and subsequent development of new phenotypes. Evolution serves the phenomenon of life, but not separate living bodies. Perishable organisms are used by Nature only as tools for transforming the permanent planetary system of life. For mortal individuals, heredity is useless, variability is harmful, evolution is unnecessary, and reproduction can be dispensed with. Living bodies have a set of properties that distinguish them from inanimate ones. It is impossible to single out one property that determines the living. It is their complex that determines a qualitatively new state of a biological system. On the basis of a complex of structures and properties, living bodies have a variety of emergent functions and means that contribute to their survival.

Part VI

Reproduction and Development

Chapter 9

Self-reproduction of Genomes and Living Bodies

The existence of individual life, that is, the existence of each individual cell or multicellular organism, is physically and genetically limited in time (see Chap. 11). The main reason for the deterioration and destruction of organisms is their inevitable degradation based on the second law of thermodynamics (Sect. 7.4), which is only temporarily overcome by them thanks to genetic programs for maintaining integrity (Chap. 12). The dissipation and death of living bodies are unescapable. Therefore, only their incessant reproduction on a planetary scale can ensure the replacement of inevitably aging and dying organisms. Reproduction is one of the main properties of living bodies, the basis for the long-term existence of all species of organisms, as well as a prerequisite for maintaining the immortal planetary system of life and the existence of the phenomenon of life.

9.1 The Purpose of Reproduction All biological species of organisms consist of separate individuals, each of which sooner or later dies. But, despite this mortality, owing to the ability of individuals to reproduce their own kind, the life of species and the existence of the planetary system of life will not terminate. What is more, the reproduction of individuals is only important for the emergence of new organisms in taxonomic groups, and has no value either for maintaining the vital activity of the organism itself, or for its selfrepair, or for extending its life. Individuals of any species can breathe, eat, move, and remain alive for a certain period of time without any need for reproduction. That is, reproduction is a necessity only for the constant renewal of the composition of populations, species, and the planetary system of life, but it is not a critical necessity for the existence of an individual life. Constant reproduction of individual cells to replace those whose cellular life cycle is complete is of great importance for multicellular organisms. It is known that the overwhelming majority of cells live much less long than the tissues, organs, © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_9

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or organisms that they constitute. The long-term functioning of these systems is ensured by the constant division of stem cells and replacement of old cells with new ones. Thus, the continuous reproduction of short-lived cells leads to long-term maintenance of the structure and function of organs and tissues. That is, the ability of cells to reproduce is the basis for maintaining the life of multicellular organisms, but is irrelevant for the duration of their own life. Thus, the phenomenon of reproduction of genomes and reproduction of living bodies is the basis for the long existence of biological systems, but does not have any influence on the lifetime of the individual units composing their structure. At the same time, the ability of living bodies to reproduce determines a number of very important properties of the phenomenon of life. Such important life phenomena as heredity and variability are impossible without the reproduction of genomes, just as natural selection and evolution are impossible without the reproduction of organisms. All of these phenomena occur at the level of populations and species, but are determined by the properties of each individual offspring. That is, the process of reproduction is a very important property of living bodies, although it does not serve those living bodies themselves, but rather the system in which they exist. Reproduction of organisms is based on DNA replication, together with duplication of the genome and its transfer to daughter organisms. It is the genome that is the main actor in this general process of generating and maintaining the permanence of the life system. Only the genome possesses the property of continuity, which is passed on to subsequent generations, ensuring the immortality of the phenomenon of life. This means that reproduction is in fact the process of duplication by genomes with their own further transfer into daughter organisms using the properties of living bodies in which they live. Moreover, when a new daughter organism appears, life as a phenomenon does not appear anew out of nowhere. A daughter organism is just a new phenotypic framework for the immortal genome as it travels across time and space. From the perspective of living bodies, reproduction is a process of procreation of new individuals belonging to their own species, but not procreation of themselves! And from the perspective of a genome, reproduction is the process of procreation of that genome itself using for this the living bodies in which they live. That is, procreation of living bodies is based on the reproduction of genomes. Thus, the purpose of the reproduction of individuals (including humans) is not their own personal interest, but is a hidden task aimed at instinctively maintaining the qualitative and quantitative composition of their species of genomes in the global system of life. This is done by means of the continuous replacement of inevitably dying bodies with the new ones. By their death and reproduction, organisms exclusively serve the eternal well-being of the egoistic global system of genomes, which in principle has no concern for the fate of each of their derivatives. Organisms do not need to reproduce in order to live, yet they live in order to reproduce.

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9.2 Types of Reproduction Every biological species of organisms consists of separate individuals. Each of them has a limited lifespan. The long-term existence of biological species, over millions of years is ensured by the constant reproduction of individuals. Each multicellular organism consists of separate structural and functional units, namely, cells. The life of almost all cells is shorter than the life of an individual (for example, the average life of mammalian cells is 20–30 days), so the long-term existence of each organism is supported by the replacement of old cells with new ones, which is ensured by the reproduction of stem and committed cells. Thus, self-reproduction of living bodies is a necessary condition for the long-term existence of each type of living organism, as well as the permanence of the planetary system of life. The methods of reproduction of living organisms are very diverse. Conventionally, they are divided into two types: (1) asexual reproduction and (2) sexual reproduction.

9.2.1 Asexual Reproduction This type of reproduction does not involve the formation and fusion of gametes, nor changes in the genetic material and information of the genomes of an individual or its descendants. In unicellular organisms, this is a division based on the preliminary doubling of DNA and the subsequent uniform distribution of daughter genomes into different cells. Multicellular organisms can also have asexual reproduction, known as vegetative reproduction, where body parts or a group of somatic cells serve to generate the progeny. With asexual reproduction, the resulting offspring are genetically identical to the parent organism. This is the most ancient approach, which appeared simultaneously with the emergence of life about 3.5 billion years ago. Asexual reproduction is highly efficient and permits rapid generation of large amounts of offspring. However, it does not provide additional genetic diversity for individuals, and this limits the effectiveness of natural selection. Main characteristics: (a) only one parent is involved in the reproduction process; (b) there is no transformation of the genome and no formation and fusion of gametes (there is no gametogenesis or fertilization); (c) the procreation of organisms is based on DNA replication, reproduction of the genome, and then mitotic distribution to daughter organisms; (d) new individuals can develop from the somatic part of the parent organism; (e) daughter organisms are genetically identical with each other and with the parent organism; (f) the process ensures a rapid increase in the number of individuals; (g) the unit of reproduction can be the whole body of a parent, part of the body (vegetative reproduction), or a single somatic cell. Significance. Asexual reproduction is generally characteristic of prokaryotes, unicellular organisms, and many fungi and plants. It is also of great importance

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for animals, since successive mitotic divisions ensure formation of all the individual cells of a multicellular organism, resulting in differentiation and growth, as well as enabling regeneration of tissues and organs. The advantage and special significance of asexual reproduction lies in the rapid and efficient increase in the number of individuals carrying a particular genome. After beneficial mutations in the genome, successful traits of individuals quickly spread in the population, and this contributes to evolution and survival. Under conditions of constant change in the environment, it was the asexual reproduction and reproduction of a huge number of unicellular species that ensured the rapid spread of successful combinations of genes in nature. Organisms in which asexual reproduction predominates (bacteria, many protozoa and fungi) are enormously productive. It was asexual reproduction that enabled life to penetrate almost every corner of the Earth and form a powerful planetary system. Various methods of asexual reproduction of genomes have ensured the survival of numerous species of living bodies and the highest stability for the phenomenon of life for billions of years.

9.2.2 Sexual Reproduction This type of reproduction is realized through development of a new individual from a zygote as a result of fertilization—the fusion of female and male gametes. In this case, there is a transformation (crossing over during meiosis) and the unification of the haploid genomes of the parents with different alleles, which leads to the appearance of genetically modified diploid offspring. Many multicellular living organisms use this type of reproduction, since they are not able to reproduce by parts of the body. In addition, this has a number of advantages over asexual reproduction, since the appearance of genetically and phenotypically diverse offspring contributes to their adaptation and evolution. Sexual reproduction arose approximately 1–1.5 billion years ago. It was based on the processes of replication, recombination, mitosis, and meiosis. The principles and basic processes of sexual reproduction have survived to this day and are similar for all kingdoms of organisms.

9.2.2.1

Germ Plasm Theory

In 1883, August Weismann formulated the theory of the “immortal” germ plasm. Knowing nothing about genes and genomes, he first suggested that the wide variety of somatic cells of organisms (trophoplasm) ultimately serve to preserve the “hereditary substance|” of the germ plasm (idioplasm) and transfer it through time from one generation to the next via gametes. He argued that death is not a general law of nature, since it is absent in prokaryotes and protozoa. The individual life of the simplest cells (for example, paramecium) ends not with death, but with the division of the mother into daughter cells. The latter grow,

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and then in turn multiply by division, and so on. According to Weismann, unicellular organisms are potentially immortal, and death arose only with the emergence of multicellular organisms. They possess cells differentiated into germ (reproductive) cells, which provide for reproduction, and somatic (bodily) cells, which compose the body. The “germ plasm” of germ cells has retained potential immortality, and gametes serve as perpetual carriers of the hereditary properties of the whole organism. He believed that the hereditary characteristics of the organism are passed from generation to generation through a special “hereditary substance” contained in the chromosomes of germ cells that produce gametes. All the other cells in the body were only an auxiliary apparatus for the germ plasm. Trophoplasm (the body of organisms) was mortal, in his view, and served only as a repository and breeding ground for the eternal and unchanging germ plasm. The body developed from the germ plasm, all its hereditary characteristics being determined by the “hereditary substance” of the germ plasm, but the soma itself did not affect the germ plasm. The germ plasm remained unchanged, being transmitted from generation to generation during reproduction, while the trophoplasm was transient and was created by the germ plasm only in order to protect itself from damage and facilitate reproduction. The germ plasm theory was ahead of its time, containing the correct concept of the presence in living bodies of the two most important interdependent components that determine life. However, the presence of a “continuous germinal pathway”, as well as “trophoplasm and idioplasm”, which Weisman considered to be the general properties of living matter, is not a feature of all species of organisms. It is absent, for example, in prokaryotes, as well as in the primitive eukaryotic organisms. This pathway is inherent only in sexually reproducing organisms. From our point of view, the unifying principle of the organization and existence of all living bodies is the possession of two key structural and functional components: the genome and the phenome (see Sect. 2.6). This is inherent in any living organism from bacteria to humans. It is the principle of monolithic coexistence of genome and phenome that can unite all living bodies into a single “team”. The genome is an immortal apparatus for reproduction and life management (Sect. 13.8) (analogous to the “immortal germ plasm”). The phenome or phenotypic framework (analogue of the “trophoplasm”) is the protective, maintenance, and executive system of the genome (Sect. 18.2). Between these two systems, it is the genomes that are the key in any type of reproduction, using their own phenotypic framework to achieve that purpose (Sects. 9.6–9.8).

9.2.2.2

The Main Characteristics and Significance of Sexual Reproduction in Mammals

(a) two individuals, one male and one female, usually participate in sexual reproduction, the exception being hermaphrodites; (b) the process is characterized by DNA replication, the formation of gametes, and fertilization, during which genetic information of two genomes is transformed and integrated; (c) one of the stages of reproduction (gametogenesis) includes meiosis, which involves the processes of

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crossing over and genome recombination; (d) sexual reproduction is characterized by high genetic variability, that is, daughter organisms differ from parents and from each other in the allelic composition of genes, while variants of hereditary material appear due to new combinations of genes during crossing over of chromosomes in meiosis, and random divergence of chromosomes and random fusion of gametes during fertilization; (e) the units of sexual reproduction are haploid gametes; (f) the rate of sexual reproduction is relatively low, due to the time required for the formation of gametes, the search for a sexual partner, fertilization, and the development of a new organism. Significance of sexual reproduction. (a) The emergence of sexual reproduction was a significant stage in the evolution of life on Earth, and one of the reasons for further progress in the diversity of living organisms. (b) During sexual reproduction, there is allelic modification and mixing of the genomes of two parental individuals of a given biological species. Their offspring are genetically different from each other and from their parents, which leads to the genetic and phenotypic diversity of individuals of this species. The genetic roles of the father and mother in determining the characteristics of the offspring are virtually equal (the same contribution to the formation of a common genome), despite the huge difference in the size and structure of the egg and sperm. However, only the maternal line contributes through the oocytes to transmission of mitochondrial DNA, cytoplasmic organization, and factors of initial development. (c) In the process of the cycles gametogenesis → fertilization → multicellular organism → gametogenesis → and so on, old combinations of genes in the genomes disintegrate and new ones are created. (d) Sexual reproduction makes the population competitive in conditions of unpredictable environmental variability, and promotes evolution due to the appearance of new characters in individuals. (e) In a large population, sexual reproduction helps to consolidate favorable alleles and remove unfavorable ones. (f) Sexual reproduction contributed to the emergence of diploid genomes. Diploid organisms have the important advantage of having two copies of every gene. These copies can mutate and serve as source material for the creation of new traits, without leading to fatal consequences in the event that a new trait is inadequate to the current state of the environment. Diploidy gives stability to the body, since a harmful or lethal mutation of one of the copies of a gene is usually recessive and does not bring about any tangible harm. In many multicellular organisms, the diploid phase is complex and prolonged, and the haploid phase is simple and short-lived. During the diploid phase, immediately after the fusion of gametes, the cells of the embryo multiply and specialize, forming a complex multicellular organism. (g) Animals have germ cells, from which originate the subsequent generations of gametes, and somatic cells that form the rest of the organism. Somatic cells are needed practically only for the maintenance of germ cells, and in particular, their reproduction, survival, and maturation. (h) Sexual reproduction limits the accumulation of lethal recessive alleles, since if both heterozygous parents carry the same lethal mutation, then their homozygous offspring will perish. (i) Due to the high combinative variability, the sexual process ensures the emergence and spread

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of useful genes and traits. (j) Periodic “rewriting” and “editing” of genetic information in the process of each reproduction cycle ensures its stability and the long-term stability of the genetic individuality of a given species. Once again, we note that, at the moment of fertilization, life does not arise anew. All that happens is that genomes are transferred from one individual to another, resulting in the appearance of new living bodies. Hence, it is also true that the orderliness of a living cell, which is one of the main characteristics of life, does not arise anew. It is already present in the ovum and then remains in the zygote. So, an equally important process during reproduction is the continuous transmission of the orderliness of the cytoplasm of the dividing cell and its constituent parts to subsequent generations. Here, the information about the organization and principles of functioning of molecular systems of the cell is transmitted from generation to generation in a non-genetic way. Then, through repeated cloning of a genome and orderliness in the process of cell division, a new complex multicellular organism appears, carrying its genome like a baton of life, ready to pass it on to the next generation.

9.2.3 Gametes as a Transitory Form of Genomes Sexually reproducing organisms possess molecular and cellular mechanisms for “conserving” and “packing” their genome in the bodies of gametes to be transported to a new organism. In particular, special germ cells, known as cells of the embryonic pathway (gonoblasts), are already isolated in the early stages of development of the mammalian embryo. These primary germ cells actively migrate through the cell layers of the mesenchyme in the embryonic wall of the hindgut and into the thickness of the genital ridges, which turn into primary gonads. There, the gametogenic epithelium of the gonads is formed and the gametes are produced. Germ cells are unique, as only they are capable of forming haploid gametes—unicellular organisms, which are a transitory form of the genome of multicellular organisms. This group of cells ensures the continuity of the life process of a given species of organisms, or one might say, the continuity of a given species of genome. A variety of diploid somatic cells form the bodies of organisms. The bodies are, as it were, secondary to the cells of the germline. Somatic cells only create conditions for fully fledged long-term functioning of the system of gamete production and the spread of genomes. Thus, in multicellular organisms that reproduce sexually, two fundamentally different types of cell are distinguished: 1. Somatic cells that form all the different tissues, organs, and parts of the body. There are several hundred of these types of cells, distinguished by their structure and functions. They make up the vast majority of cells in the body. The genetic material of the genomes of these cells is divided only by mitosis. Such cells generally have a diploid set of chromosomes. The main purpose of somatic cells

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is to build a body as the phenotypic framework of its genome, to ensure its functioning, survival, and reproduction. 2. Germ cells. Primary germ cells separate in early embryogenesis and populate the primary gonads of the embryo. In the epithelium of the gonads, they are present as diploid spermatogonia or ovogonia. Only they are able to form the mature haploid germ cells. Germ cells can divide both by mitosis (the period of reproduction in gametogenesis) and by meiosis (the period of maturation of gametes). The main purpose of germ cells is to form gametes as a transitory form of the genome, and the main task of the gametes is the continuous transfer of the genome from one generation of organisms to the next. Gametes can exist outside the body for some time, and even fertilize independently of it. The common and unifying element of these two cell lines (somatic and germ) in multicellular bodies is the genome, which plays two paramount roles in ensuring life (see Fig. 14.1): replication determines the reproduction of genomes, and their expression determines the development of living bodies. The genomes of germline cells or somatic cells do not differ in terms of information content. Their significant morpho-functional differences are associated only with their contrasting differential expression. Due to the need to perform different functions, male and female gametes are phenotypically very different from each other. Egg cells are maternal gametes adapted for fertilization by sperm and intended for development into an adult organism. In mammals, the egg cell genome has a haploid set of autosomes and one sex chromosome, the X chromosome. An egg is a highly specialized cell with unique characteristics. It is usually a large, spherical, immobile gamete with voluminous cytoplasm, enclosed in several membranes. It contains all the typical cellular organelles and substances necessary for the development of the embryo, in particular, the nutrient material in the form of yolk granules, which include various proteins, phospholipids, and neutral fats. The structure and size of the eggs are specific to each animal species. Some species of animal accumulate so much yolk that the eggs are visible to the naked eye (the eggs of fish and amphibians, and the yolks in the eggs of reptiles and birds). Other important components are also accumulated in addition to the yolk. For example, substances necessary for the processes of replication, transcription, and translation, which includes thousands of crucial enzymes, ribosomes, mRNA molecules, and tRNAs. Additionally, cytoplasm contains special regulatory substances that coordinate the functioning of all cell structures. There are special enzyme proteins that destroy nuclear envelopes, factors of condensation and decondensation of chromosomes, formation of pronuclei, factors of cytokinesis, and so on. Therefore, the embryo does not use the genetic and energy resources of blastomeres in the first stages of cleavage. This ensures the onset of embryogenesis without the intake of any substances from the outside. Egg cells are generally much larger than somatic cells. In birds, the egg cell is actually what is considered to be the yolk in everyday life. The diameter of the yolk of an ostrich egg is about 6 cm, and that of a chicken about 2 cm. The eggs

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of animals whose embryos receive nutrition from the maternal organism, and in particular mammals, are much smaller in size. For example, the diameter of a mouse egg is about 60 µm, and that of a human egg about 100 µm. Spermatozoa are mature male germ cells intended for the transfer of the male genome into the ovum. They generally have the ability to move actively, making it possible for gametes to meet. The genome of mammalian spermatozoa contains a haploid set of autosomes and one sex chromosome, either the X or Y chromosome. In terms of structure, size, and function, sperm cells differ significantly from the egg and somatic cells. These are usually long, narrow cells with a head, neck, midsection, and tail. The front part of the head contains an acrosome formed by a modified Golgi complex. Most of the head is occupied by a nucleus containing the genome, with densely packed genetic material. The tail is formed by an axoneme microtubule, containing a bundle of protein fibrils covered with a membrane. The size of the sperm is generally very small. For example, in domestic animals (dog, bull, horse, ram), the length of these cells is around 40 µm, and their thickness is 1–2 µm. The volume of mammalian spermatozoa is thousands of times less than the volume of the egg cells. Despite the significant differences between male and female gametes, the content of species-relevant hereditary information in their genomes is equivalent. In the process of evolution, they acquired morphofunctional features for performing special functions: (1) packing of the genome and its temporary conservation; (2) transportation of haploid genomes; and (3) connection of the parental genomes. Gametes are unique cells in sexually reproducing multicellular organisms. They are a temporary, transitory form of the genome’s existence, constituting a haploid phase in the life of a multicellular organism. Only gametes, like shuttles, can physically ensure the processes of genome transfer and the transfer of hereditary information from one generation of living bodies to another, thus guaranteeing the genetic continuity of life. In specific cases, body parts can also serve as shuttles for the transfer of genomes to subsequent generations of both sexually and vegetatively reproducing organisms.

9.2.4 Gametogenesis is the Process of Transformation of Genomes Gametogenesis is a set of sequential processes of proliferation and formation of mature germ cells from generative precursors. The development of gametes in mammals occurs in the gonads. Spermatogenesis is the process of formation of haploid spermatozoa from diploid reproductive cells (spermatogonia) in males. In mammals, this process takes place in special paired glands, the testes. Oogenesis is the process of formation of haploid eggs in females from diploid reproductive cells (ovogonia) of the ovaries.

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Several important processes modify the genomes of the cells of the embryonic tract during the complex multistage processes of gametogenesis, in order to adapt them to fertilization and development of a new body, where they will live on (Fig. 9.1). Gametogonia develop from the primary germ cells that migrate to the gonads at an early stage of embryogenesis. Upon reaching puberty, they rapidly multiply via mitosis. Genetic transformation of the ploidy and allelic composition of their genomes occurs during the first division of meiosis (see Sect. 9.5), while the completion of the second division of meiosis results in differentiation into mature haploid gametes with a unique set of alleles. As a result, due to the special way the germ cells divide, numerous modified gametes are formed from standard, diploid gametogonia, containing haploid genomes with diverse allelic composition (see Figs. 9.1, 9.4, and 9.6). The process of transformation of genomes of generative cells is accompanied by significant changes in their phenomes. In particular, during spermatogenesis, large, round, classical-looking cells with a large nucleus turn into small headed and tailed spermatozoa containing a small nucleus. And during oogenesis, huge, round eggs with large nuclei are formed, surrounded by several membranes. After fertilization, a spherical zygote is formed from two such different cells. This divides and gradually turns into a fully formed embryo. In this way, genomes gradually adapt their phenotypic framework for their far-reaching goals.

Fig. 9.1 Scheme of genome transformations in the process of gametogenesis, fertilization, and division of a zygote. 1—In the process of meiosis, the diploid replicated genome of gametogonia is modified into the haploid genome of gametes with altered allelic composition. 2—In the process of fertilization, haploid gametes form a diploid zygote with the combined allelic composition. 3—In the process of mitotic division of the replicated diploid genome of a zygote, diploid blastomeres of an embryo are formed

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9.2.5 Fertilization as Integration of Genomes Fertilization is the penetration of a sperm genome into an egg, which entails three important events: (1) activation of the egg; (2) fusion of haploid genomes; and (3) the formation of a diploid zygote as the initial unicellular stage of development of a new organism. In humans, as a rule, one spermatozoon penetrates into one egg cell. This is the phenomenon of monospermy. However, in insects, fish, birds, and some other animals, several gametes can enter the cytoplasm of an egg. This phenomenon is called polyspermy. The role of polyspermy is not entirely clear, but it has been established that the genetic material of only one of the spermatozoa (male pronucleus) fuses with the female pronucleus. Consequently, only this sperm is involved in the transmission of hereditary information. Other gametes are destroyed. Since the binding of a sperm and an egg is species-specific, only the sperm of one species, carrying own kind of genome, can bind and fertilize the egg. This is based on the molecular mechanism of recognition and binding, which is carried out by species-specific receptor macromolecules. This is one of the main mechanisms for maintaining the “purity” and constancy of the genome of a given biological species. The main event of the fertilization process is the fusion of the paternal and maternal genomes (Figs. 9.1 and 9.2). The entry of the sperm nucleus into the cell stimulates the secondary oocyte to complete the second meiotic division, which results in separation of the second polar body. The sperm genome in the cytoplasm of the egg “swells” and reaches the size of the egg nucleus. Proteins that have retained a compact, inactive state of sperm chromatin are removed, which leads to chromatin decondensation. Large male and female pronuclei are formed from the nuclei of the sperm and the egg. The male pronucleus and the female pronucleus move towards each other. This rapprochement process lasts several hours. At this time, DNA replication occurs in each pronucleus, followed by condensation of chromatin by histones and the formation of chromosomes. The centrioles diverge to different poles and form a spindle apparatus. When the pronuclei come into contact, their membranes are destroyed and two sets of chromosomes (maternal and paternal) are mixed (amphimixis) in the central part of the cell. As a result, a diploid set of chromosomes is formed, containing 2 chromatids. The fertilized egg is now called a zygote, which begins rapid mitotic division. As a result of the first mitosis of the zygote, each chromosome is divided into chromatids, which diverge to its different poles. This is followed by cytokinesis with the formation of two blastomeres of the embryo. In this way, a new diploid organism is formed as a result of the fusion of female and male haploid genomes.

9.2.6 The Zygote as the Beginning of a New Life for Genomes The development of all sexually reproducing organisms necessarily involves the zygote stage (Figs. 9.1 and 9.2). A zygote is a fertilized egg, a single-celled embryo

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Fig. 9.2 The main events taking place with the genetic material of parental genomes at the initial stages of embryogenesis. 1—Completion of meiosis II after penetration of the sperm nucleus. 2—Formation of pronuclei and DNA replication. 3—Formation of chromosomes in pronuclei. 4— Karyogamy (amphimixis). Union of the father’s and mother’s chromosomes. 5—Metaphase of the first division of a zygote. The father’s and mother’s chromosomes are located randomly along the equator of the cell. 6—Anaphase. Each chromosome is divided into separate chromatids. 7— Telophase. Chromosomes unwind and form a chromatin network, which gets covered by the nuclear envelope. 8—Cytokinesis. Two cells are formed that contain the mixed genetic material of the father’s and mother’s genomes

of a future multicellular organism. It contains haploid genetic hereditary materials of the paternal and maternal organisms combined into a single diploid genome. Although the sperm and the egg have the same genetic potential, the egg contributes significantly more to the development of the future organism. Its cytoplasm contains a large number of various regulatory molecules (mRNA, peptides, etc.), without which the development of a new body would be unrealistic. Moreover, widespread in various taxonomic groups is the phenomenon of parthenogenesis, which permits the development of fully fledged organisms even from an unfertilized egg, after it has been stimulated by certain factors! These properties of the ovum, and then of the zygote, are determined not only by the genome and the presence of many developmental determinants, but also by the presence of a high degree of internal structural and functional orderliness. After fertilization, this ordered organization of the egg is inherited by daughter cells determining the standard course of metabolic and cytogenetic processes in the offspring. It can be said that the transfer of structural and functional orderliness to descendants by division is the inheritance of phenotypic information (see Chap. 18). In this case, vital information is transmitted in the form of the organized structure of the extremely complex system of cytoplasmic molecules. It is an ordered colloidal matrix in which (and by means of which) the genome implements the software for the process of individual life.

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After fertilization of the egg, significant ordered movements of the cytoplasmic components occur in the newly formed zygote. This plays a decisive role in the differentiation of the future embryo, since different cytoplasmic morphogenetic determinants (morphogens) enter each blastomere during cleavage, and through the genome, these determine the fate of subsequent blastomeres. Morphogens are mainly specific regulatory and functional proteins and peptides, as well as messenger and short-chain RNAs. Determinants define specific pathways of differentiation of embryonic cells, as well as the development of tissues and organs. The complex processes of embryo development are based on the genetic programs of the new diploid genome and their selective implementation. Controlled cleavage and differentiation of blastomeres occurs on the basis of differential expression of genes in the genome (Fig. 9.1). Each stage in the development of a living body is associated with the expression of a specific part of the genome in each blastomere. The final version of a phenome is formed after the completion of the sequential implementation of all the necessary information of the genome. Thus, a zygote possessing a genome and determinants is a cradle for the emergence of a new individual life.

9.3 Division of Cells and Their Genomes The growth and development of a multicellular organism, for example, a mammal, is provided by the massive formation of somatic cell lines as a result of division of a zygote: the cells of an embryo, fetus, and newborn. In an organism, cells live for a limited time, less than the individual itself (see Sect. 11.1). Gradually, they wear out, age, and die. However, division of stem or committed cells provides an effective way of ensuring their permanent reproduction. In addition, there is a cytogenetic mechanism for the formation of gametes via the division of a line of special generative cells. Thus, cell division provides for the three most important aspects of the life of multicellular organisms: (a) reproduction of individuals; (b) growth and development; (c) self-repair and maintenance of homeostasis. Eukaryotes possess two types of division, depending on the cell line and the peculiarities of genome transformations: 1. Vegetative division (mitosis), characteristic of somatic cells, during which the genome does not change and after which each daughter cell is genetically identical to the parent cell. 2. Reproductive division of cells of the reproductive system (meiosis), realized through allelic modification of the genome, where the number of chromosomes in the daughter cells is halved. Once formed, cells live and function until they divide again or die. “Cell from cell” is one of the basic postulates of the cellular theory of life, which states that new cells appear only from previous ones. To this can be added the postulate: “genome from genome”, given that it is the genome’s metamorphoses during division that are

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decisive for future offspring, and it is the genome that is leading and controlling all aspects of the life of living bodies. Many cells of multicellular organisms, both stem and committed cells, have the ability to divide multiple times. The sequence of events between divisions is called the cell cycle. This is a set of cytogenetic and biochemical processes aimed at the cell’s functioning and subsequent reproduction. The cycle is characterized by a variety of events occurring in the cell under the control of the genome: growth, differentiation, functioning, replication, mitosis, and so on, and is subdivided into several phases and periods. From the point of view of cell life, it is conventionally divided into three main phases: interphase, mitosis (or meiosis), and cytokinesis. And, from our proposed point of view of genome transformations (Table 9.1), this corresponds to: (a) functioning and duplication of the genome, (b) termination of functioning, compaction, and fragmentation of the genome into separate chromosomes convenient for transfer, and (c) decompacting of chromosomes and formation of an integral functional genome in daughter cells. We now consider the main phases of the cell cycle from the point of view of genome metamorphoses (Fig. 9.3).

9.3.1 Interphase This is the part of a cell cycle between the end of cytokinesis and the beginning of mitosis. Interphase is the main active period of cell life, when most of the resources are spent on maintaining vital activity, growth, development, and functioning. At the same time, it is during the period of interphase that a key event takes place that lays the foundation for subsequent division—replication (doubling) of DNA, which is the basis for the formation of a new genome. The interphase consists of three consecutive phases: G1, S, and G2. The G1 phase, or pre-synthetic phase, begins from the moment cytokinesis ends (Figs. 9.3 and 9.4). The nucleus contains two homologous chromosomes of each pair. Each chromosome of the genome consists of one unwound strand of chromatin. This is the longest stage in the life of a functioning cell. Transcriptional and translational activity during the pre-synthetic phase is at the maximum level: the genome actively controls the synthesis of the various RNAs and proteins needed to combat entropy, for cell growth and development, and to perform various functions. The S phase, or synthetic phase, is the phase of DNA doubling in the genome. In all chromosomes in the cell, replication occurs almost simultaneously, resulting in the formation of an identical copy of each DNA strand. These two copies remain linked by a centromere. DNA replication is a critical event in the cell and genomic cycle. It is the S phase in which genetic material and the information in the genome is copied, leading to the formation of the two equal sets of DNA which will serve as the basis for the formation of new genomes in the daughter cells. After DNA duplication, the cell can no longer return to the G1 phase, but must necessarily divide.

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Table 9.1 Metamorphoses of the mammalian genome and phenome during the cell cycle Phases and stages of the cell cycle

Genome transformations

Phenome transformations

Interphase

The genome is mainly represented by the contents of the cell nucleus

The phenome is represented by the cytoplasm covered by the cytoplasmic membrane

G1 phase

The genome is represented by an unwoven, functioning chromatin network

The phenome functions under the control of information coming from the genome. The organelles and cytosol function normally to ensure the life of the cell and its genome

S phase

The genome is represented by an unwoven, functioning chromatin network. Replication of the network of all DNA molecules of the genome takes place

The phenome functions under the control of information coming from the genome. The organelles and cytosol function normally to ensure the life of the cell and its genome

G2 phase

The genome is represented by two linked copies of each DNA molecule. Condensation of chromatin begins

The cell increases in size, and the synthesis of ATP, proteins, RNA, lipids, and carbohydrates is enhanced. The centrioles divide, forming two cell centers. The size of the nucleus and the amount of heterochromatin increase

Mitosis

The genome is represented by chromosomes

The phenome is represented by the changing cytoplasmic environment of the genome during the phases of mitosis

Prophase

Condensation and spiralization of chromatin occur in the genome. Formation of chromosomes begins

The centrioles diverge to the poles of the cell in the cytoplasm. The spindle apparatus begins to form

Prometaphase

The genome forms separate chromosomes, consisting of two linked copies of DNA (two chromatids)

The membrane of the nucleus is disintegrated into membrane vesicles in the cytoplasm. Certain other organelles are also disintegrated

Metaphase

In the genome, the chromosomes are maximally compacted, consisting of two chromatids. The chromosomes line up in the middle of the mixoplasm. The genome halts its activity

The nucleus disappears in the cell. The karyoplasm mixes with the cytoplasm. The mixoplasm forms

(continued)

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Table 9.1 (continued) Phases and stages of the cell cycle

Genome transformations

Phenome transformations

Anaphase

In the genome, the chromosomes are split into two separate chromatids (into two daughter chromosomes), which move to different poles of the mixoplasm. The genome is divided in half

The protein filaments of the spindle apparatus pull the daughter chromosomes to opposite poles in the mixoplasm

Telophase

The condensed daughter chromosomes of the two separated genomes are unwound to chromatin. A membrane forms around each genome and a nucleus is produced. At this stage of mitosis, the two daughter genomes, represented by two equivalent sets of chromosomes, coexist in the cytoplasm of a single mother cell

The spindle apparatus is disintegrated in the mixoplasm and organelles and two nuclei are formed again. The nuclear structure of the genomes is restored, consisting of genetic material and the enzymes and other tools needed to manipulate genetic information

Cytokinesis

Division of daughter genomes is carried out by dividing the body of a bi-nuclear mother cell into two daughter cells. Their genomes are again represented by the contents of the nuclei, which again become functional

Two daughter cells form, containing equivalent genomes in the same phenotypic framework as before

Fig. 9.3 The main phases in the life of a dividing cell (“cell cycle”). The cell cycle includes a long interphase, a shorter period of mitosis, and an even shorter period of cytokinesis. The interphase consists of the G1 , S, and G2 phases. Mitosis includes prophase P, prometaphase PM, metaphase M, anaphase A, and telophase T. Division is completed by cytokinesis C. Cytokinesis is associated with the natural loss of the maternal cell accompanied by the formation of two daughter cells containing copies of the maternal genome. Since the division ends with the loss of the mother cell, its period of life can in no way be called a cycle. Only a genome is truly cyclical, because it does not disappear anywhere, but circulates again and again from one body to another

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Fig. 9.4 Cytogenetic transformations of the genome during the cell cycle. The genome undergoes amazing transformations during division. During the S phase of the interphase, its informationalmaterial component doubles. Then, during prophase and metaphase, a huge compartment of the nucleus disintegrates, unifying its contents with the cytoplasm to form the mixoplasm—a single space for operating with the carriers of genetic information. At the same time, the whole system of unwound active chromatin is transformed into a set of isolated compact chromosomes. Simultaneously, special tools and mechanisms are being created to move individual carriers of genetic information. During anaphase, the chromosomes are divided into separate chromatids and move to different sides of the mixoplasm. Further, in the telophase process, the nucleus is restored and the chromosomes are unwound, forming the typical genetic network of a genome. And after cytokinesis, the structural and functional state of the genome is completely restored to the form of a single system of active chromatin. These complex processes are carried out by invisible molecular metabolic reactions that provide the genome with matter and energy. That is, it is obvious that the genome cleverly uses the resources of the phenotypic environment for its own purposes. Moreover, even when inactive, the genome still guides the processes of its own transformation through the intermediaries it has previously formed in the cytoplasm. Mitosis is also a good example of cellular macroprocesses associated with the transformation and movement of vast amounts of organized cellular structures (see Sect. 7.8)

The G2 phase, or post-synthetic phase, occurs after the completion of replication. The cell prepares to divide. The cytoskeleton is rearranged, the condensation of chromatin begins, and the synthesis of ATP, proteins, RNA, lipids, and carbohydrates is enhanced. Special regulatory proteins are synthesized to facilitate the cell’s transition from G2 to division. Centrioles divide, forming two cell centers. The nucleus grows and the amount of heterochromatin increases. The cell also grows in size. The interphase ends and the genome enters the prophase of mitosis. It should be noted that many cells of a multicellular organism (neurons, erythrocytes, cardiomyocytes, keratocytes, etc.) lose their ability to divide as a result of deep differentiation. This state of a cell is called the G0 phase. In this phase, cells actively

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perform specific functions, but their genome has lost the ability to enter the S phase of the cell cycle. These highly specialized cells die without leaving offspring after working out the time allotted to them. Their place is taken by cells developing from stem cells, the genome of which always retains the ability to divide and differentiate. There is a pool of stem cells in every tissue.

9.3.2 Mitosis Genomes of eukaryotic cells at the interphase stage always contain several unwound chromosomes (sometimes tens or even hundreds). These chromosomes must be precisely evenly distributed among the daughter cells during division. In the event of an error, both daughter cells may be defective and even non-viable. There are special cell mechanisms for the precise separation of the genetic material of a genome. The most common way of dividing genetic material after replication is mitosis, a process in which two genetically identical daughter genomes are formed from one maternal genome (Fig. 9.4). During mitosis, each X-shaped double chromosome splits into two chromatids, each of which is directed to one of the two daughter cells. Since the chromatids of one chromosome are the results of exact matrix copying, both daughter genomes receive the same genetic information. Separation of chromosomes is a complex biomechanical process that requires external motor activity, since chromosomes are not capable of independent movements. Therefore, the movement of chromosomes during mitosis is carried out by the spindle apparatus, which is a set of microtubules that extend from the cell center and attach to chromosomes. The process of mitosis is conventionally divided into a sequence of five phases: prophase, prometaphase, metaphase, anaphase, and telophase (Fig. 9.4). In prophase, the genome is still represented by a solid nucleus, whose volume increases, while light and dark areas are formed due to the spiralization of chromatin and the beginning of the formation of dense chromosomes. By the end of prophase, each chromosome consists of two chromatids visible under a light microscope. The genome gradually loses its activity in the regulation of the metabolic and functional processes of the cell. Its activity switches to the regulation of the processes of its own transformations and separation. The centrioles begin the formation of the spindle apparatus. In prometaphase, the nuclear envelope is gradually destroyed and the karyoplasm is gradually united into a single space with the cytoplasm. Separate chromosomes are randomly located in it. The intracellular organelles disintegrate and the centrioles diverge to the opposite poles of the cell. The genome is represented as a compact set of chromosomes. In metaphase, the nucleus completely “dissolves”, its contents combine with the cytoplasm, and the mixoplasm forms. But the genome, which exists as a sum of chromosomes, i.e., a karyotype, does not disappear. The chromosomes reach their maximum density and are arranged in an orderly manner in the middle of the cell. During metaphase, chromosomes have a concise structure and are clearly visible

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under a light microscope. Therefore, the study of karyotypes (counting their numbers and studying the forms and structure of chromosomes) is carried out precisely at this stage of division. During this period, each chromosome consists of two chromatids which have already diverged somewhat at the ends, whence the chromosomes have a classic X-shape. Thus, the genome at the metaphase stage is represented by a set of maximally spiralized chromosomes, arranged in an orderly manner. Their genetic material is in a “conserved” state and cannot perform its executive activity. In anaphase, each double X-shaped chromosome is finally split into two chromatids, which are from this point on called daughter chromosomes. The spindle fibers attached to their centromeres contract and pull the daughter chromosomes to the opposite poles of the mother cell. It is at this point that the previously doubled genome divides in half. In telophase, both sets of daughter chromosomes located at the poles of the cell unwind and acquire the structure of chromatin threads, and this is accompanied by the gradual return of inherent genetic activity. At each pole, a nuclear envelope is formed around the unwoven chromosomes from the membrane vesicles of the mixoplasm. The genomes are fully formed and acquire the classic shape of nuclei with concentrated genetic material, along with the whole set of enzymes and other tools required for manipulating genetic information. The spindle apparatus is disintegrated and all the organelles are formed again. At this stage of division, two daughter genomes, represented by two equivalent sets of chromosomes, coexist in the same cytoplasm of the single maternal cell. Cytokinesis. During the telophase, a cleavage furrow is already formed along the perimeter of the equatorial zone of the cytoplasmic membrane of the mother cell, gradually deepening into the cytoplasm. This process involves special protein fibrils capable of contraction. When the cleavage furrows are connected in the center of the cell, the daughter cells become completely separated. As a result, the final distribution of genomes occurs between the daughter cells. These genomes are genetically identical to each other, having a full set of DNA molecules and enzymes necessary for the implementation of all genetic information. Table 9.1 outlines the joint interdependent transformations of the genome and its phenotypic framework during the cell cycle of somatic cells in mammals. Here, in the macroprocesses of cytogenetic transformations of the genome, a colossal amount of cell masses are transformed and moved (see also Sects. 7.8 and 9.4). From the above, as well as from Table 9.1 and Fig. 9.4, it follows that all metamorphoses of the genome during the cell cycle are also accompanied by significant transformations of its phenotypic framework. Moreover, all changes in the constituent parts of the phenome and the appearance of new structures at various stages of the cell cycle are clearly aimed at servicing structural and functional changes in the genome, as determined by a specific goal. That is, despite the temporary shutdown of activity of the genome during mitosis, its phenotypic environment functions according to the program written by the genome even before division gets under way.

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9.3.3 Chromosomal Cycle The genetic material of the genome of a multicellular organism is discrete, since it consists of several DNA molecules, several chromosomes, many genes, many intergenic regions, many gene networks, and so on. The genome demonstrates reversible changes in the structure and shape of chromosomes during the cell cycle (Table 9.1, Fig. 9.5). During the G1 phase of the interphase, it is represented by a chromatin network, consisting of the sum of unwoven chromosomes. In the preparation of the cell for division (S phase), the chromatin network doubles (DNA replication). During prophase, chromatin is compacted by spiralization. By the end of the prophase, chromosomes are formed from chromatin. They are represented by separate, shortened and thickened chromosomal bodies. In metaphase, they become even shorter and more compact, acquiring an X-shape and a certain structure and size. During anaphase, the chromosomes divide into two chromatids. In the telophase, the chromosomes again adsorb water, unwind, and form the chromatin network characteristic of the interphase. Then the cycle can be repeated many times. Such repetitive operations of genetic material can be called a genomic or chromosomal cycle. Conventionally, this genomic cycle can be divided into three fundamentally different periods: (a) the reproductive period, which involves processes associated with the duplication of genome DNA supermolecules in the S phase of the interphase; (b) the period of division, which involves the processes of distribution of genetic material of the genome during mitosis; (c) the functional period, where genetic information of the genome is implemented during the G1 and G0 phases of the interphase. The chromosomal cycle results in the exact distribution of the set of sister chromatids (sister genomes) between the daughter cells. Each daughter cell of a new generation receives one of two copies of the maternal genome. Thus, the processes of the chromosomal cycle ensure its doubling, division, and relocation to a new body.

Fig. 9.5 Chromosomal (genomic) cycle during the cell cycle. Transformations of just one chromosome from the entire karyotype are presented. Explanation in the text

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Fig. 9.6 Cytogenetic transformations of the genome and its phenotypic framework during meiosis. Explanation in the text

This chromosomal-genomic cycle repeats constantly, ensuring the permanence and constancy of the genome over time in an endless series of cell generations.

9.4 Meiosis Even more impressive metamorphoses happen with the genome and its phenotypic framework during meiosis. Sexual reproduction is based on the formation of gametes, with the genome containing a haploid set of chromosomes. In this case, one of the specific tasks facing a diploid eukaryotic cell is a twofold decrease in ploidy in order to form

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germ cells. This is solved by a special form of division of the genetic material in the genome of germline cells which is called meiosis. It results in the formation of four haploid daughter cells from one diploid mother cell of the reproductive tissue. These daughter cells are genetically distinct from the mother cell from which they are derived. Extraordinary processes occur during meiosis, accompanied by fascinating transformations of the genome (see Figs. 9.1 and 9.6). Division of the genetic material of the genome is preceded by the replication of the DNA of the gametogonia. This is followed by two successive divisions of genetic material (called meiosis I, or reduction division, and meiosis II, or equational division) (Fig. 9.6). As a result of reduction division, daughter cells get one chromosome from each pair; there is a transition of the genome from the diploid to the haploid phase. As a result of equational division, X-shaped chromosomes are divided into two chromatids, which are passed on to the daughter cells of the second generation. In the classical case, the reduction and equational stages each comprise two divisions, which is why, as a result of meiosis, one maternal genome generates four daughter genomes. Meiosis I is preceded by interphase, during which each DNA molecule of the genome of the gametogonia is replicated. Therefore, each chromosome of a dividing cell consists of two sister chromatids linked by a centromere. Reduction division. The first meiotic division is conventionally divided into several stages. Just like mitosis, meiosis I is subdivided into prophase, prometaphase, metaphase, anaphase, and telophase (see Fig. 9.6): Prophase I is subdivided into several stages, during which genetic recombination of the genome occurs: • Leptonema. In this stage, condensation of genomic chromosomes is observed. The chromatin reticulum spirals and organizes into clearly visible chromosomal strands with a protein axis. Each such chromosome is attached by telomeric and centromeric regions to the nuclear membrane. Although each chromosome DNA has already doubled and consists of two sister chromatids, they are still very close together. For this reason, all the chromosomes appear as single separate strands. • Zygonema. In this stage conjugation occurs, a temporary close connection of homologous chromosomes with the formation of bivalents, structures consisting of two connected chromosomes. At the moment when the homologous chromosomes join, each gene comes into contact with the allele homologous to it. • Pachynema. In this stage crossing over occurs, an exchange of sites between homologous chromosomes. Homologous chromosomes remain connected to each other. • Diplonema begins with the separation of the conjugated chromosomes. The complex gradually disintegrates and homologous chromosomes are separated from each other. • Diakinesis. Here, double chromosomes are greatly shortened and condensed, followed by separation from the nuclear membrane. At this stage, it is already clear that each bivalent contains four separate chromatids. The nuclear envelope

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is destroyed and a spindle apparatus begins to form, attaching itself to the kinetochores of the chromosomes. The chromosomes condense to a maximum, synthetic processes stop, and the centrioles diverge to the poles. Prometaphase I. The nuclear membrane is fragmented and forms membrane vesicles, evenly distributed throughout the cytoplasm. The nucleus “disappears”. Genomic chromosomes are immersed in the mixoplasm. They become accessible to the spindle microtubules, which attach to the chromosome kinetochores and regulate their movement. The centrioles migrate to the poles of the cell and spindle filaments are formed. Metaphase I. The bivalent chromosomes line up along the equator of the cell, with the centromeres of the chromosomes located exactly along the equatorial line at an equal distance from the poles of division. The orientation of each bivalent occurs independently of the others. Anaphase I. The bivalents separate and homologous chromosomes diverge to opposite poles of the cell. In this case, whole chromosomes diverge to the poles, each consisting of two chromatids, and not separate chromatids, as in mitosis. Telophase I. Chromosome sets separate and completely diverge into opposite parts of the cell. A nuclear envelope gradually forms from membrane vesicles around each new set of chromosomes. The latter can partially unwind and lengthen somewhat; a fully fledged nucleus containing a modified genome is formed. Cytokinesis I. After the end of the telophase, the body of a mother cell divides. As a result, after the first meiotic division, the genome of each daughter cell contains one of the sets of homologous chromosomes. Interkinesis is the period between the first and second divisions of the genome during meiosis. This period of the cycle is usually very short or may be completely absent. Replication of the genetic material does not occur during the short interphase. Each chromosome initially consists of two sister chromatids. Thus, after the first meiotic division, the altered genome is represented by the haploid number of chromosomes in each daughter cell (gametocyte). But each of the chromosomes contains two DNA molecules. Equational division of the genome. The second division of meiosis immediately follows the first, without a pronounced interphase; the S phase is absent, since DNA replication does not occur before the second division. The mechanism of the second division in meiosis is similar to that of mitosis, i.e., its essence is the division of chromosomes into separate chromatids. This stage is also conventionally subdivided into 5 phases (Fig. 9.6). Prophase II. Re-condensation of chromosomes occurs. Prometaphase II. The cell center divides, and the products of its division (centrioles) diverge to the poles of the nucleus. The nuclear membrane is destroyed, and the spindle apparatus is formed. Metaphase II. X-shaped chromosomes are located at the equator of the cell, at an equal distance from the “poles” of the nucleus, forming a metaphase plate. Anaphase II. The chromosomes divide into two chromatids, which diverge towards the poles.

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Telophase II. The chromosomes are despiralized and stretched out, taking on the appearance of chromatin; a nuclear envelope and a fully fledged nucleus are formed. This is followed by cytokinesis II. In the resulting gametes, the genome is represented by a haploid set of chromosomes, each of which consists of one DNA molecule. In the cases where meiosis is associated with specialized gametogenesis (for example, in mammals), some of the resulting cells degenerate. In these animals, during the development of oocytes, only one of the cells turns into a gamete, and the other three form the so-called polar bodies. It should be noted that all the above-listed processes of meiosis are primarily associated with operations on genetic material. Consequently, the essence of the process of sexual reproduction is cytogenetic manipulation of the genome of germ cells and its transit, through sexual partners, across a number of generations. Informational-cytogenetic transformations of the genome during meiosis. Consecutive stages of meiosis, fertilization, and development are associated with parallel cytogenetic and informational processes occurring with the genome (Table 9.2). That is, the genome should be viewed as a tool for manipulating both matter and information. See Chaps. 13, 14, 18, and 19 for details. Significance of meiosis. In sexually reproducing organisms, meiosis is one of the main stages in the formation of gametes that carry a haploid genome to the next generation. Meiosis is the basis for variability in the genome of sex cells. It creates an opportunity for the emergence of new combinations of genes as a result of crossing over and the breakdown of homologous pairs. The distribution of chromosomes among the daughter cells is random in both metaphases of meiosis. Hence, the offspring never look identical to their parents or other offspring. As a result, each subsequent generation of genomes and organisms has some new traits and new combinations of traits, and this contributes to adaptation to various environmental Table 9.2 Examples of informational-cytogenetic transformations of the genome during meiosis Cytogenetic processes

Informational processes

Replication of DNA molecules

Copying and duplicating genetic programs of the genome

Crossing over

Partial transformation of the genetic information in genomes

Chromosome formation

Archiving the genetic programs of the genome

Formation of four haploid genomes

Separation and transmission of transformed genetic programs into four daughter cells

Formation of haploid gametes

Formation of a transitory form of existence of the haploid genome and genetic information in the phenotypic framework of mature germ cells

Fertilization and zygote formation

Merging of genetic programs of male and female haploid genomes to create the diploid genome of a new organism

Formation of multicellular organism Implementation of the genetic program of the diploid genome during the development of a new organism

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conditions, and hence to evolution and survival. As in the case of mitosis, so in the case of meiosis, metamorphoses of the genome are caused and accompanied by profound changes in the phenotypic framework. What is more, the modification of a phenome is always aimed at maintaining the genome. Even in spite of the almost complete conservation of a genome during meiosis, operations on it continue through its phenotypic environment, according to the program recorded by the genome before the start of division and preserved in the partially unwound parts of the chromosomes. The processes involved in the chromosomal cycles of genomes ensure their reproduction, division, and relocation to other bodies. Such genomic cycles are repeated many times, ensuring the permanence and constancy of genomes over time and through a number of generations of living bodies.

9.5 The Role of the Genome in Reproduction Organisms possess many different strategies for both sexual and asexual reproduction. Various species of animals, plants, and other organisms, depending on their habitat and their level of evolutionary development, manifest all sorts of variations in their reproductive anatomy and physiology. However, the common basis for all types of reproduction is molecular genetic processes, and primarily the replication of DNA molecules. These molecules form chromosomes. They are the hereditary material of an organism and they also contain the information necessary for the birth of a new life and the development of a body. Replication leads to a doubling of the hereditary material of the genome, which is then passed on to daughter cells in equal amounts through mitosis or meiosis. In this respect, DNA molecules are unique in relation to all other molecules of living nature. We call them stem molecules (see Sect. 14.1, Fig. 14.1). The nucleic acids in a genome control the synthesis of proteins, which are constantly renewed in cells. Through the synthesis of proteins, the genome regulates the formation of new bodies and the renewal of virtually all organic molecules found in cells, thus ensuring the long-term survival of the various species of living organisms that inhabit our planet. The above discussion makes clear the central role of genomes and genetic mechanisms in the processes of reproduction and development. During fertilization, the DNA in the gametes carries hereditary information from the parents to the next generation of individuals. The genomes of heterosexual organisms merge during fertilization and form a zygote, whose genotype is a new system of interacting genes and the basis for the development of a new individual. Reproduction can be considered as a means of cloning and distributing individual genomes in the global genome network. Even during vegetative propagation, for example, when a plant propagates by cuttings, a mass of cells containing the same genome is separated along with the separated part of the plant’s body. It is its differential expression that ensures the development of a new organism. And with artificial cloning, a foreign nucleus, being the receptacle of another genome, is transplanted into a denucleated egg. It is this

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genome of the transplanted nucleus that gives the informational basis for building an organism peculiar to it (and not peculiar to the egg cell). These examples demonstrate the leading role of genomes in reproduction. The role of ploidy in reproduction. Prokaryotes are permanently haploid creatures. That is, their genomes have only one chromosome (one circular DNA) per nucleoid. They multiply by preliminary replication of the DNA molecule, chromosome duplication, and subsequent mitotic division. Multicellular organisms spend most of their life cycle in a diploid form, i.e., the genomes in the cells of their bodies possess a double set of chromosomes. Only for a short period of the life cycle do they exist in the form of haploid gametes (Figs. 9.1, 9.2 and 9.7). It is believed that the diploidy of immature gametocytes permits crossing over between homologous chromosomes at meiosis during the formation of haploid gametes, which provides for a colossal variety of allelic variants. Therefore, after fertilization, the number of genetic and phenotypic versions of diploid offspring increases exponentially. Trillions of phenotype variants provide a high probability of their partial passage through the sieve of natural selection, thus guaranteeing the long-term existence and evolution of their species of genome. Moreover, diploidy is a way to protect against harmful mutations, since most of them are recessive. Thus, for most sexually reproducing multicellular organisms, the life cycle is characterized by an alternation of haploid and diploid periods of life (Fig. 9.7). Moreover, for most multicellular organisms, the diploid period of existence in the form of an adult is the main one. In this stage, the majority of somatic cells contain a double set of chromosomes. And the existence of an organism in the form of a haploid living body of gametes is a forced transitional period of life, necessary only for the reproduction of a genome and its phenotypic framework. Such haploid genomes of gametes in multicellular organisms are formed as a result of meiotic division of the diploid genomes of germline cells. Gametes, as a special form of existence of the Fig. 9.7 The cycle of existence of a genome of Homo sapiens, as an example of the alternation of haploid and diploid periods in the individual life of multicellular organisms. 1—The period of existence in the form of haploid gametes. 2—The period of existence in the form of diploid organisms

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individual life of an organism, are capable of an autonomous existence for a certain period of time, even outside the body of the producer. In the case of successful fertilization, a new diploid multicellular organism develops from the already diploid zygote by mitosis, and this organism becomes once again a producer of unicellular haploid living bodies. At a certain stage of their life cycle, some adult diploid organisms (individual plants, algae, fungi) can fully exist for a long time in both the diploid and haploid forms. For example, the horsetail (a kind of plant) can exist in the form of two fully fledged bodies: in the form of a diploid vegetative shoot and a haploid prothallus (Fig. 9.8). There are also some animals (for example, insects such as bees and aphids) whose life cycle includes the alternation of mature diploid bodies, haploid bodies, and haploid gametes (see Fig. 9.9). Their genomes are thus fully active, in the case of both a single and a double set of chromosomes. The above examples indicate that despite the huge variety of life cycles in the existence of living bodies and the variety of ways they can reproduce, in all cases, the main role is played by the transformation of genomes, which never disappear, no matter what temporal forms their phenotypic framework may take. Consequently, the genome is an immortal dynamic self-regulating structure that can exist in different forms of ploidy, depending on its life cycle. It is also obvious that, in the life cycles of mortal organisms, it is the genome and only the genome that undergoes a permanent cyclic transformation. It passes periodically from one

Fig. 9.8 Diploid–haploid life cycle of the horsetail Equisetum arvense L. In the haploid stage of the life cycle, horsetail cells multiply by mitotic division. A haploid multicellular body of a gametophyte is formed, with its own features of the phenome, whereas diploid cells of such organisms are formed from haploid ones as a result of the sexual process (fusion of haploid germ cells) with the formation of a zygote. After this, the cells of the embryo can multiply by mitotic divisions with the formation of a diploid multicellular body of a sporophyte. Here, none of the states in the genome’s existence is more important than any other

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Fig. 9.9 Haploid–diploid life cycle in the bee Apis mellifera. The species of the bee genome can exist (live) in the haploid bodies of the egg and sperm, in the diploid zygote, in diploid and haploid larvae, in haploid drones, and in diploid queen bees and working bees. In this case, we can say that the genome rather determines, not the sex of these organisms, but the characteristics of the social purpose of their bodies

form of existence to another, differentiates, and building a further mortal phenotypic framework around itself, returns once more to the original form of a monolithic body. Depending on the nature of the changes in the ploidy of the genome, the following kinds of life cycle are distinguished: • Haplophase cycle. During the entire cycle, haploid organisms have a single set of chromosomes (n) in their genome. They multiply by mitotic division of a maternal organism into a daughter after replication. Such life cycles are characteristic of prokaryotes and protists that do not have a sexual process. • Haplophase cycle with zygotic reduction. In such haploid organisms, after the formation of a zygote (2n), meiosis occurs, whereupon the remaining stages of the life cycle are haploid. In particular, such a life cycle is characteristic of many green algae, as well as some groups of protists and fungi. • Diplophase cycle with gametic reduction. The main stages in the life cycle of such organisms are diploid (2n); only the gametes after meiosis are haploid (n). This life cycle is typical for animals, for instance. • Haplo-diplophase cycle. At both the diploid and haploid stages of the life cycle of organisms, mitotic divisions occur, leading to reproduction or growth. In the life cycles of such organisms, for example, in some plants (horsetail), both diploid and haploid generations are present. It may seem that these kinds of reproduction and life cycle of organisms are significantly different, that they have nothing in common, and that nothing unites them. However, we emphasize once again that, in all the cases listed above, the main character is the genome. It can be haploid, diploid, or even polyploid, but it is only the genome which, by different means and strategies, is transmitted to subsequent generations. It is believed that immediately after the emergence of life, the only phase of the life cycle of unicellular creatures on Earth for hundreds of millions of years was the haploid phase of the genome. When the seasons changed or under unfavorable

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conditions, the vegetative bodies formed into small spores. In this state, it was much easier to survive the unfavorable period. It is believed that, under certain conditions, the spores could have merged and temporarily formed bodies with a diploid genome. Under favorable conditions, after the replication of the genetic material, its meiotic division was carried out, and vegetative haploid organisms were formed from the diploid spore again. With the emergence of multicellular organisms, there was a change in the priorities of ploidy in the life cycle of living bodies. The duration of the diploid phase of the genome’s existence increased, and it was transformed into an autonomous multicellular organism. In this case, the role of the short-term haploid phase of the genome in the form of gametes was reduced only to the reproductive function, and it began to serve for the reproduction of the main diploid body. But, despite the change in ploidy priorities, the essence of both the first and second methods of reproduction is the transit of genomes to subsequent generations of the living bodies. Therefore, it can be noted once again that all organisms are derived from genomes and are only a convenient means for ensuring their existence, copying, and cloning. It should also be noted that multicellular organisms are characterized by both monoeciousness (hermaphroditism) and dioeciousness (sexual dimorphism in the form of the presence of female and male organisms). That is, the genome can equally well be located in one body and produce two kinds of gamete, or in two bodies, each of which produces one kind of gamete. It can be placed in many diverse bodies, such as happens in bees (Figs. 9.9 and 11.1), where there is a queen bee, drones, and workers (unable to produce gametes). Obviously, the division of individuals according to sex or social purpose is not decisive in the existence and reproduction of the genome, but is only a consequence of its adaptation through a variety of phenotypic frameworks (see Chaps. 18 and 19). Hence, the reproduction of genomes and their cellular environment is the main survival mechanism of the genomes themselves. Nothing else but the genomes of millions of species of living organisms can travel over tens of millions of years from one mortal body to another, guaranteeing the constancy of their species and the permanence of the phenomenon of life on Earth. That is, the genomes are the part of life that constantly survives in the fight against inevitable entropy.

9.6 Transit of Genomes It is known that the lifespan of the overwhelming majority of somatic cells in multicellular organisms is much shorter than that of the tissues and organs, or the organisms themselves, which are composed from these cells. The long-term functioning of these systems is ensured by constant division and replacement of old cells with new ones, which then grow and develop. It follows from the previous section that the essence of reproduction during division is the transcellular transfer of genomes.

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And the essence of the reproduction of multicellular organisms is the transorganismic transfer of genomes through the mechanisms of reproduction. These mechanisms and the process of reproduction itself determine a number of very important properties of living organisms. Without this, such important phenomena as heredity, hereditary variation, and evolution would be impossible. Heredity is the property of living organisms to transmit to their offspring via reproduction through the genome traits that ensure the continuity of the structural, biochemical, and physiological organization over a number of generations. Heredity is based on the ability of DNA to accurately replicate and transmit stable hereditary information in the genomes from cell to cell (through mitosis) or from organism to organism (through both mitosis and meiosis). The property opposite to heredity, associated with the appearance of traits that differ from the typical inherent ones, is called variation. Variation is based on the property of DNA genomes to mutate and recombine. Thus, the hereditary variation of genomes creates the prerequisites for evolution and speciation through natural selection of new phenotypes of living bodies. Thus, it is obvious that the transorganismic transfer of genomes, as transmission of genomes, is carried out in the process of reproduction. It follows from this that the main function of cells and multicellular organisms is to preserve the genome, to maintain its structural and functional integrity, and to transfer it. They serve as transmitters, i.e., as a kind of framework for the transfer of genomes. Cells carry out the transcellular transfer of genomes, and multicellular organisms the transorganismic transfer, ensuring the permanence of life (Fig. 19.3). In turn, viruses and mobile genetic elements carry out transgenomic gene transfer within the single system of the global genome (Sect. 14.7, Fig. 14.7). In general, all types of genome transfer should be called transits, since they only linger for a short time in their current phenotypic framework, and in the case of successful reproduction, immediately migrate to other bodies.

9.7 Exchange of Living Bodies (and Genomes) Thus, the ability to reproduce is inherent in living bodies, but does not serve those living bodies (Sect. 9.1). It rather serves to maintain the number and qualitative composition of species that form a single planetary system of life. That is, reproduction of genomes and living bodies enables the existence of the global heterogeneous planetary system of organisms, which has maintained the phenomenon of life on Earth for billions of years. This virtually immortal system is maintained and renewed through two complementary properties of organisms: the death of the old and the reproduction of the young. From this it follows that we do not belong to ourselves. We belong to this planetary system. And the ability to reproduce, although it belongs to us, does not serve us. It serves the phenomenon of life. The human population of the world is over 7.9 billion, and every second it increases by several people. It would seem a very simple fact. But behind it there is an invisible process of the most intensive exchange (renewal) of the individual composition of

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humankind. Thousands of people die and are born every second. But still, a few more individuals are born than die. In fact, about 2 million people die and are born every day. The intensity of this process is so great that every month about 60 million appear and the same number leave for another world. Approximately 750 million people are renewed annually, which is more than 10% of the total population of the Earth. This “imperceptible” process of constant exchange of living bodies has been supporting the life of the species of genome of Homo sapiens for thousands of years, maintaining its qualitative and quantitative composition, and even leading to its continuous growth. A change of generation, which is based on the exchange of living bodies, occurs in humans roughly every 25 years. Indeed, during this time, the individual composition of humanity is radically renewed. Inevitable death and indispensable birth govern life. Nature is not interested in the question of the social importance of an individual. It is only interested in the individual’s biological purpose, equal for all living bodies: the recycling of genomes and the maintenance of the permanent phenomenon of life. The process of self-renewal of the individual composition of populations is characteristic of absolutely all genetic groups living on the planet, regardless of their level of development and lifespan. Moreover, in many species, the intensity of exchange of living bodies is much greater than in humans. The smaller the representatives of the species, the more intensively they reproduce and the faster they renew the composition of the population. For example, the lifespan of a fruit fly (Drosophila melanogaster) is about 30 days. During this period, females are able to lay about 400 fertilized eggs 5–6 times. Larvae appear from the eggs after 24 h, and grow for five days. They then undergo a five-day stage of metamorphosis and turn into adults, which after 8–12 h are ready to reproduce and renew their population. After 20– 30 days, completely new representatives appear, which are also seriously involved in reproducing their genomes. Similar processes occur among all living organisms—archaea, bacteria, protists, plants, fungi, and animals. Moreover, the lifespan is different for individuals of different species, but this does not matter for the eternity of the global process of exchange of living bodies. Nature mercilessly destroys the carriers of life, which cannot exist forever, but gives them enough time to guarantee reproduction and transfer their genomes to the next temporary generation (Chap. 19). It is exactly the phenomenon of the exchange of living bodies and genomes that is the basis for the long-term existence of biological species, and ensures the immortality of the phenomenon of life.

9.8 Reproduction as a Means of Survival for Genomes The reproduction of genomes and cells is a complex process that has its own peculiarities in different species (see Sect. 9.5). But at the heart of all types of reproduction of

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cells and organisms lies replication, i.e., duplication of DNA, the formation of homologous chromosomes, and the subsequent division of duplicated genetic material into the genomes of daughter cells. That is, the essence of the process of “cell division” is actually the division of the copied hereditary material of the genome. The cell is just a secure environment where this event can take place. At the time of division, the cell loses its typical appearance—the membrane of the nucleus disappears, the nucleus disappears, the organelles and cytoskeleton are lost, and the nuclear-cytoplasmic mixture, or mixoplasm, is formed within the volume of a cell, possessing completely different contents and other properties. That is, the cell dramatically transforms its structure and functions. It has completely new goals and objectives aimed at servicing the processes of chromosome formation and genome division. In this way, new macrostructures are formed. Tens of DNA strands are packed into large chromosomes, and the powerful polar, kinetochore, and astral protein microtubules of the spindle apparatus appear. Other macroprocesses take place. The chromosomes split, the chromatids are set in orderly motion, and a protein constriction forms, gradually separating the duplicated daughter chromosomes into separate compartments of the mother cell. Then the chromosomes are grouped together, losing their compactness and unwinding to form chromatin. The spindle apparatus is disassembled and the nuclear membrane is formed once again. By this time, cytokinesis is complete, the mother cell “disappears”, and the daughter cells separate from each other and regain their standard appearance. Thus, it is obvious that it is the genetic material that undergoes dramatic transformations, and the cells, in this case, play an auxiliary role. In the end, the dividing cells disappear forever, and the genome is always kept constant. Once again, we note that the reproduction of genomes, the reproduction of cells, the death and change of generations of organisms are unique and integral properties of life. No matter how perfect the processes of maintaining the specific structure of cells, the life of a single celled or a multicellular individual sooner or later comes to an end, so continuation of life as such becomes possible only as a result of the reproduction of their genomes. That is, the death of living bodies is a lethal event only for themselves, not for their genomes. The infinite duration of any individual life would be physically impossible (see Sect. 11.1), since organisms cannot endlessly resist both entropy and the changing environmental conditions with one standard fixed set of structures and properties. These structures and properties must also change in accordance with new circumstances. Unchanging standard organisms, no matter how long they existed, would inevitably die during the transformation of the conditions of existence, since they could not ensure viability. Only those organisms have survived whose genome has had time to mutate and adapt along with their phenome, and also to consolidate new useful information in the genetic apparatus during the reproduction process. With typical ingenuity, Nature, in addition to natural physical ways of limiting the lifespan of individuals, also limited them genetically (see Sect. 11.1), to be absolutely one hundred percent certain of the destruction of aging living bodies and the ongoing transformation of their generations, something which is critically necessary for the evolution and survival of the phenomenon of life itself. This limit was thus introduced

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and fixed in the genome of each individual, thereby limiting its lifespan. But at the same time, Nature endowed living bodies with the ability to reproduce and provided them with sufficient time for reproduction of the genome, providing the conditions for its survival and further evolution. If we consider individual reproduction on the scale of the planetary system of life as a means for ensuring the survival of genomes, it becomes clear that on this basis there will always be a constant global renewal of its variable components, ensuring the permanence of existence.

9.9 Summary The main reason for the limited time of existence for cells and organisms is their inevitable degradation based on the second law of thermodynamics. But for the phenomenon of life as a continuous global process, unfolding in space and time, this obstacle is surmountable due to the continuous self-reparation and reproduction of its constituent living bodies. The inevitable death of the phenomes and the infinite reproduction of the genomes of living bodies is the essence of the continuous process of life. All cells are formed as a result of division: the division of the body of a mother cell into two daughter individuals. This is preceded by a doubling of the genetic material of the genome. Once formed, cells live and function until they divide again or die. Despite the variety of characteristics of cell cycles in different organisms, reproduction can be reduced to several basic processes, characteristic for all of them: DNA replication, the formation of double chromosomes, separation of chromosomes, and cell division. In the process of dividing, daughter cells of eukaryotes must receive a complete copy of the parental diploid genome (mitosis), or at least its haploid half (meiosis). Preparing for division, the cell makes a complete copy of all the hereditary information of the genome and then carefully divides the copies and safely transfers them to the resulting daughter cells. However, this is hindered by the gigantic size of DNA and its chaotic occurrence in the nucleus. Therefore, immediately before division, the thin, intertwined DNA molecules of the genome are ordered, compacted by repeated spiralization, and turn into autonomous chromosomes. The chromosomes diverge to the poles of the cell due to the activity of the spindle apparatus and, after division, they separate into new daughter nuclei, where their chromatin unwinds again and forms an active genome system. The combination of these events is the chromosomal, or genomic cycle. The process of reproduction results in transcellular or transorganismic transfer of genomes, living bodies are just convenient means and tools for copying and cloning those genomes. Therefore, the purpose of the reproduction of individuals is not their own interest, but the survival and maintenance of the qualitative and quantitative composition of their species of genome. The process of updating the individual composition of populations and species underpins the permanence of

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the phenomenon of life, while the essence of reproduction is the process by which genomes reproduce themselves using the bodies in which they live.

Chapter 10

Development or Self-construction

Multicellular organisms are characterized by the presence of a specific pattern and sequence of developmental processes from their genesis in the form of a single cell to the adult multicellular organism. In essence, this is a process of self-construction, another critically important property of living bodies, along with self-reproduction and self-reparation (see Sect. 5.6). Among the most illustrative examples for demonstrating the mechanisms of autoconstruction are the processes occurring after reproduction, during the development of representatives of the class of mammals. Therefore, in the rest of this chapter, we will briefly overview the developmental processes in mammals from the point of view of the importance of the genome.

10.1 Genesis and Individual Development Most multicellular organisms, including mammals, have cycles of reproduction and development (Fig. 10.1), which include several important processes: the formation of germ cells (gametogenesis), their subsequent fusion (fertilization), development of the organism, and puberty. The genomes of the parents are combined at the moment of fertilization, a new organism is born, and a new living body appears. Thus, the life of mammals, as the autonomous existence of a separate organism, begins from the moment of fertilization—fusion of the parental haploid genomes. A diploid zygote is formed, followed by development, on the basis of the division mechanism, of the whole variety of cells, tissues, and organs of a multicellular organism. The complex of sequential, relatively slow processes from the moment of appearance of a zygote to the formation of a complex mature multicellular organism, with a large number of differentiated cells, tissues, and organs, is called ontogenesis or individual development. Ontogenesis is a dynamic process during which an organism gradually changes its phenotypic characteristics, while maintaining, however, the same single genome.

© Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_10

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Fig. 10.1 The cycle of reproduction and development of mammals, taking the example of Homo sapiens. The purpose of individual development is the creation of sexually mature bodies as producers, carriers, and distributors of genomes. 1—gametogenesis, 2—fertilization, 3—division, 4—differentiation, 5—growth and development, 6—puberty

Ontogenesis is based on selective, sequential, differential expression and implementation of hereditary information of the genome at all stages of development. During ontogenesis, the hereditary information of the genome is gradually realized in the aggregate of certain morphological, biochemical, physiological, and other characteristics of the organism, accompanied by the complication (ontogenetic evolution) of the structural and functional organization of the organism. Ontogenesis of multicellular organisms goes through several stages of development and ends with the death of the organism (Table 10.1). Ontogenesis is a consequence of the fixation in the genome of a long process of phylogenetic development. The interconnection between individual and historical development is reflected in the biogenetic law: ontogeny recapitulates phylogeny. All modern animals contain the same clusters of developmental genes in their genomes. Their commonality, single mechanism of action, and single principle of embryonic development testifies to the existence of a common ancestor. A frog, a dog, or a human are just variants of the general project of building a living body, which was already “developed” in the first multicellular organisms. All events of ontogenesis are closely linked to each other by a certain space (body) and time (sequence and direction of processes). The development of the embryo, and then the body, is a decentralized self-controlled process, since in different parts of it, the formation and growth of completely different organs and tissues occurs simultaneously. The developmental process is self-informational. Each prior state carries information about the direction of future events. The principle of reflexivity of development is implemented here, i.e., one event sets the starting conditions for the other events, etc. Apparently then, the process of development of living bodies is not based entirely on the genetic information in the genome. Genetic programs are the main

10.1 Genesis and Individual Development Table 10.1 The main periods, stages, and processes of individual development

263

Periods

Stages

Processes

Pre-embryonic

Primordial germ cells ↓ Gametes ↓

← Gametogenesis ← Fertilization

Embryonic

Zygote ↓ Blastula ↓ Gastrula ↓ Embryo ↓ Fetus ↓

← Cleavage ← Gastrulation ← Histo- and organogenesis ← Growth and development ← Birth

Post-embryonic

Newborn ↓ Juvenile organism ↓ Sexually mature organism ↓ Old organism ↓ Termination of vital processes

← Growth and development ← Puberty ← Aging ← Death

element initiating and controlling the process, which is additionally controlled by the emerging and changing structures, and develops rather like a snowball rolling down a hillside, on the basis of additional structurally determined information (phenotypic information). Thus, ontogenesis in multicellular organisms is a conditioned process in which the state and conditions of the previous stage affect the events occurring in the subsequent stages of development. For example, the formation of limbs in mammals begins only when the embryo reaches a certain size and shape. The process of ontogenesis is characterized by discreteness and integrity. Two cells are formed as a result of the first division of a zygote, becoming the first constituent parts of a new biological system which will become an emerging complex organism, consisting of immense number of cells. From this moment on, the development of the embryo is determined not only by the genetic programs of a genome and phenotypic information, but also by the relationship between cells and elements of the emerging system. Each subsequent stage of development (blastula, gastrula, neurula, etc.) is a new state of the developing unified system. At any given stage of development, this system is a new entity (and not just a sum of cells), in which all its cellular elements are deeply integrated and interconnected. The interconnection and interaction of the parts of the developing embryo gradually change in the process of development.

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Ontogenesis of mammals is subdivided into several periods and stages of development, each ensured by special processes of differential expression of the genome (Table 10.1): 1. Pre-embryonic period. This period is also called progenesis (preceding ontogenesis). Its basis is gametogenesis—the formation of mature germ cells, which is a condition for repeating the cycle of individual development of subsequent generations of organisms. The autonomous existence of gametes after gametogenesis and before fertilization is an intermediate link in the existence of life between the ontogenesis of the parents and the ontogenesis of the offspring, an existence in the haploid genome form. Fertilization is the process of gamete fusion, resulting in the formation of a diploid cell, or zygote, which is the initial stage of development of a new organism. Fertilization entails the two most important processes: karyogamy, which is the unification of the paternal and maternal genomes, and activation of the egg (induction of development). Fertilization determines the beginning of a new life. 2. Embryonic period. This begins from the moment when the parental genomes fuse. This event is the birth of a new body. The zygote formed as a result of fusion is a unicellular stage in the development of a multicellular organism. The embryonic period is characterized by a number of complex cytogenetic processes. Zygote cleavage is a series of mitotic divisions that proceed very rapidly. As a result, a huge volume of cytoplasm and genetic material in the zygote are fully or partially divided into numerous smaller cells, or blastomeres, which have the same or slightly different sizes. Blastomeres form a spherical blastula structure (singlelayered multicellular embryo). All blastomeres contain a variously determined parental genome. Gastrulation is a set of processes of reproduction, growth, and differentiation, along with directed movement of the blastomeres and changes in their structure and location in relation to each other. This leads to the formation of a gastrula, which consists of three layers of cells called germ layers. The outer layer is the ectoderm, and the inner one is the endoderm. Further, in three-layered animals, a third, intermediate germ layer, the mesoderm, is also formed. All three layers become sources for the rudiments of organs and tissues. Differentiation of cells occurs as a result of differential expression of the parental genome. Histo- and organogenesis constitute a set of processes of division, interaction, and movement of the cells of the germ layers. These gradually lead to the acquisition of a strict orderliness and the formation of tissues and organs in the embryo. Different organs are formed by cells originating from different germ layers. A differentiated embryo, the product of the selective expression of genomes from its different parts, is formed as a result of organogenesis. Growth and development lead to an increase in the size and mass of an organism thanks to continuous controlled division and apoptosis of cells, and an increase in the total mass of cells and intercellular substances. Gradual complication of organization and functioning takes place. Growth is an increase in the size and mass of an organism during development. Development is the gradual complication of

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the organization of the body. Growth and development are interrelated processes. They begin immediately after fertilization of the egg and occur at the molecular, subcellular, tissue, organ, and organism levels. All levels of growth and development are under the genetic control of a genome and are provided for by the differential expression of genes of the genome during ontogenesis. After the formation of the rudiments of organs, the mammalian embryo is subsequently called a fetus. These stages of development are ensured by the cytogenetic processes of cleavage, differentiation, migration of cells and cell groups, histoand organogenesis, growth, development, selective cleavage and selective death of embryonic cells, embryonic induction, and so on. Before birth, a fetus is under the protection of the maternal organism, due to its inability to perform basic functions such as breathing and nutrition on its own. Birth is the process in which the offspring organism leaves the mother’s body. The birth of an organism is followed by the establishment of a connection with its new environment, physical separation from the mother, and adjustment of the systems of respiration, nutrition, and others, thereby ensuring its further autonomous existence. Post-embryonic period. This involves stages and processes that complete rather than continue the process of development of the individual. These are growth, development, puberty, the achievement of a certain size and functionality by the body, and entry into the reproductive period. Aging is a process of gradual wear and disruption of the structure and functions of both individual cells and the whole organism. Death is the moment of irreversible cessation of the main processes and functions that support life. Hence, the processes of genesis and individual development of multicellular organisms are aimed at performing the two most important interrelated processes: 1. A zygote, and then somatic cells, form a new sexually mature organism, in which: 2. conditions and mechanisms are recreated that ensure the existence and reproduction of cells of the germline, as well as the formation of their gametes, which carry a permanent genome through space and time. The main task of each new sexually reproducing organism is the production of gametes and the transfer of genomes to the next generation. This determines the continuity of the phenomenon of life through the reproduction and distribution of genomes.

10.2 Growth and Development Development is very closely related to growth. Therefore, the terminology “growth and development” is generally used to describe the processes that are usually considered developmental. These processes begin immediately after the fertilization of the egg. Growth and development are one of the main features of all complex living organisms; they are the basis of ontogenesis. Growth and development processes occur at the molecular, subcellular, tissue, organ, and organismal levels.

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1. At the molecular level, growth is determined by the intensification of synthetic processes; primarily the synthesis of proteins, which increases the mass of the cell. 2. At the subcellular level, the construction of new membranes, enzymatic complexes, and organelles takes place. 3. At the cellular level, growth is due to hypertrophy, i.e., an increase in cell size as a result of an increase in the content of the cytoplasm. 4. At the tissue level, growth is due to hyperplasia, i.e., an increase in the number of cells as a result of their division, as well as hypertrophy, i.e., an increase in the volume of cells and intercellular substance synthesized and secreted by the cells. 5. Growth and development of organs, tissues, and the whole organism occur as a result of cell hypertrophy and hyperplasia. A multicellular organism is a clone of cells from one maternal zygote; it is a colony of identical genomes with varied differentiation and a different phenotypic framework. The formation of body parts, organs, and the body itself occurs: (a) on the basis of the multiplication of structural units, viz., cells; (b) on the basis of directed growth, systematic distribution, and location of cells; (c) due to differential expression of genes and the formation of heterogeneous complexes of cells—differentiated parts of the body. All levels of growth and development are under strict genetic control and are provided by stepwise differential gene expression during ontogenesis. The central role of the developmental process is that it is a mechanism for the formation of a complex multicellular body. In the course of growth and development, on the basis of the genetically controlled use of matter and energy from the external environment, there is a rapid increase in the number of cells and their differentiation, and also in the formation of tissues, organs, and the whole organism. The main development programs are rigidly fixed in the genomes of these organisms, being preserved and transmitted over millions of years and a multitude of generations. Evidently, it is only by understanding the mechanisms of development that we can comprehend how biological structures and processes were formed, how evolution operates with them, and how, in the end, they turn into highly complex organs, organisms, and species. The molecular genetic pathways from DNA to proteins are fairly well understood. These are the stages of transcription, processing, translation, folding, and a number of other molecular processes leading to the formation of structurally and functionally active proteins. Less clear is the path from proteins to specific macrostructures, their various forms and functions, and, ultimately, a whole autonomous living body. One feature of the growth of living organisms is its intracellular and interstitial localization. Hence, the growth of organisms occurs from the inside, in contrast to, e.g., the growth of crystals capable of increasing in size growing from the outside. In addition, the growth of higher animals is controlled by the endocrine and nervous systems through the regulation of gene expression and the metabolic rate.

10.3 Development Mechanisms in Complex Organisms

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The immature period is characterized by intensive growth, the development of all systems and proportions of the body, and the completion of the development of the reproductive system. The period of adulthood is characterized by the stability of the functions of all organs and systems, sexual maturity, and active reproduction. At this stage, growth and development stop. During the reproductive period, living bodies simply maintain a high degree of orderliness and integrity. This is followed by a period of old age with a gradual extinction of functions, a decrease in regenerative capacity, and the cessation of reproduction. The life process ends with the death of the organism. Consequently, development is a set of processes involving consistent, irreversible changes in organisms. These are natural and clearly directed, leading to the emergence of new qualities. The patterns of development indicate that it is not based on random events, but on conditioned processes. The determinism of these processes is associated with the material and informational essence of specific living bodies, and in particular, with genomic control of development, and as a consequence of genetically controlled molecular and cellular interactions. The embryonic development processes are also influenced by the spatial localization of cells, structural information, and the microenvironment. All stages of growth and development are associated with high metabolic activity of cells, primarily, with the course of numerous anabolic processes, which require a constant supply of matter and energy, provided due to the exchange of substances with the external environment. A particularly important role in metabolism belongs to the synthesis of proteins, which make up the enzymes as well as the bulk of organic mass of the cells. Thus, step by step, in the course of development, qualitative and quantitative changes accumulate. These changes manifest themselves in the formation of new systemic, structural, and functional properties of living organisms. From the point of view of thermodynamics, in the process of development of living systems, there is an accumulation of negentropy and information. The set of modifications accumulated step by step determines the direction of development of an organism, and in the end, leads to a natural result—the appearance of complete forms and the final formation of the phenotypic framework of the relevant genome. Hence, the processes of growth and development constitute a unique mechanism for the use of substances and energy by the genome to form its phenotypic framework. Growth and development underlie the emergence of new sexually mature forms of multicellular organisms which produce gametes and through their genomes transmit genetic development programs to subsequent generations, ensuring the genotypic continuity of life.

10.3 Development Mechanisms in Complex Organisms The developmental process programmed by the genome is a mechanism and algorithm for the formation of highly complex organisms. Multicellular organisms are

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indeed extremely complex in their organization. For example, a human being consists of trillions of cells of more than two hundred types arranged in an ordered manner. It has very complex organs, made up of millions of different cells, each of which is located in the right place and performs the required function. It is hard to imagine how such a complex organism, or even such a complex organ as a brain or an eye, could suddenly appear. But everything becomes more or less clear when one realizes that such complex systems appear only in the process of gradual, step-by-step development, based on the gradual differential expression of the genome of the organism. This means that differently determined genomes are selectively expressed in various parts of the body, with specific results being obtained. Then, all the information of the variously differentiated genomes can be conventionally designated as the genome of a given individuum (see Sect. 2.6, Table 2.2). Thus, complex animals do not appear in the world as integral formations, but are formed from a small group of embryonic cells in the process of embryonic and then post-embryonic development. First, the zygote genome is expressed, then the genomes of the cells of the blastula, gastrula, embryo, etc. That is, the cumulative genome of the developing organism is gradually and selectively expressed, and information from all the deterministic genomes of cells in different parts of the multicellular body is gradually brought into play. Tissues, organs, and organism appear gradually, gene by gene, cell by cell, process by process, becoming more and more complicated throughout development. For example, during human development, over the first few tens of days, a small human develops from one cell, weighing several grams, consisting of thousands of cells, but already containing all its tissues and organs, all parts of the body, and limbs. This fantastic period of embryogenesis is decisive. A highly organized organism is completely formed from a single cell through successive divisions and differentiation. It then grows, and by the time of birth is fully prepared for an autonomous existence. After birth, a human still needs 16–18 years to reach the limits of growth and development. A wide variety of types and pathways of individual development exist in nature for different vertebrates. However, all of them include variations of the processes already noted, which ensure the gradual complication of the developing organism. It is obvious that it is the purposeful development process based on the selective expression of genomes that acts as one of the main mechanisms in forming large, complexly organized, integral organisms. However, it should be noted that not all information on developmental pathways is present in the genome. For example, there is no direct information about rates, quantities, sizes, shapes, and locations of localization. Most likely, it already arises in the process of embryonic development, during which successive structural and functional changes occur continuously, that is, there is an accumulation of order and the emergence of new phenotypic information. This information can also determine the direction of further development. Each prior state carries information and an algorithm about the direction of future events. That is, genetic programs are the main, but not the only, element of the embryonic development process, which then progresses through the changing body shapes on the basis of additional structurally and spatially determined information.

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10.4 Differentiation As already noted, the formation of an organism occurs in the process of gradual, stage-by-stage development, based on the programmed differential expression of the genome of an organism. The development and long-term functioning of multicellular organisms is ensured by the following mechanisms and processes: (a) the determination and division of embryonic cells; (b) the differentiation and formation of hundreds of different cell types; (c) the formation of specially organized, differentiated parts of the body, tissues, and organs; (d) the functioning of differentiated cells for a certain time; and (e) the constant division of stem cells, which is necessary for differentiation, growth, and development, as well as for the constant replacement of dying differentiated cells. Without these mechanisms, organs, tissues, and parts of the body could not develop, function, and maintain a stable form and size for long periods. Differentiation is the process of formation of cells of various structures and functions from a zygote or stem cells in order to form and maintain the integrity of a complex organism. The specialization of cells in ontogenesis results primarily from the differential expression of genes of the genome, and also depends on the influence of cytoplasmic factors of development and the spatial arrangement and microenvironment of the cells. The biochemical basis for the presence of different traits is the presence and functioning of proteins specific to these cells. The mammalian body contains over 200 types of variously differentiated cells. These are specialized cells that have a specific shape, size, and protein composition and perform specific functions. They are formed from precursor cells on the basis of a gradual, genetically programmed change in their structure and function in the process of division, selective expression, and development. As a result, they have well defined parameters of size, shape, structure, function, and location within the tissues and organs of an organism. After that, these cells and their progeny usually do not undergo significant changes. Examples are muscle cells, cardiomyocytes, neurons, astrocytes, hepatocytes, and many other cells. The expediency of differentiation lies in the fact that cells with a certain structure and function can combine, interact, and form tissues, organs, organ systems, and parts of the body, which makes it possible for individual populations of cells of a multicellular organism to collectively perform specialized functions vital for any organism, including nutrition, respiration, reproduction, excretion, movement, and so on. At the level of a large multicellular organism, which is essentially a colony of cells of a single genome, such a differentiated structural and functional distribution is simply a necessary condition for existence. Usually, in embryos, a group of similar cells differentiates together. In such cells, the protein composition, the metabolic rate, the composition of organelles, the structure of cell membranes, the shape of cells, etc., change almost simultaneously. This process is accompanied by morphological transformations of the embryo; the rudiments of organs appear and gradually develop. Subsequently, cell differentiation limits the ability of parts of the embryo to follow a different path of development.

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The process in which a number of cells acquire the same specialization during differentiation is called histogenesis. This leads to the formation of tissues consisting of the same cells that perform similar functions. Hence, differentiation, histogenesis, and organogenesis occur simultaneously. It is important to note that completely different, independent differentiation processes take place simultaneously in different places of the same embryo on the basis of the selective expression of genes of the same genome inherited from the parents. This testifies to the strict determination of numerous individual genomes of cells of various organs and tissues on a certain path of development. This may indicate a change in the structure and functionality of the genomes themselves in different parts of the body, that is, the structural conditionality and determination of the genome of a particular part of the body to a certain path of expression. Consequently, in this case, we observe the preliminary differentiation of genomes, and then, on this basis, their selective expression. Thus, on the basis of the determination and differentiation of individual cellular genomes in different parts of the body, a differentiated embryo is gradually formed, containing all types of cells, and all tissues, organs, and body parts. Then a very complex, highly organized adult organism is formed through growth and development. This organism contains hundreds of variously differentiated cells, but initially the same genome. In an adult multicellular organism, differentiated cells with a fixed differentiated genome possess the following special features that enable the stable performance of certain functions over long periods: 1. Specific composition of proteins required to build the essential structures and perform certain functions. These proteins determine a differentiated state and a specific cell type. For example, muscle cells contain large amounts of the contractile proteins actin and myosin, and fibroblasts produce structural proteins, such as collagen, elastin, and others. 2. Differentiated cells have high metabolic activity, which is associated with the presence of a significant number of enzymes and other functional proteins. In addition to special proteins, differentiated cells have much in common with all housekeeping proteins that support the structure and energy supply of an actively functioning cell. Undifferentiated cells usually have a lower level of biochemical processes, since they practically do not function. 3. Differentiated cells have a characteristic shape and size (Fig. 10.2). Mature cells can be flat, round, square, elongated, etc., all depending on the functional requirements made on them. Specialized proteins maintain these structures. They form microtubules and filaments that make up the cytoskeleton of the cell. The cytoskeleton permeates the entire cytoplasm and maintains the shape, volume and internal structure of cells. This allows the cells to function efficiently together. Undifferentiated cells are generally oval and small in size. 4. Differentiated cells have a specific set of organelles. For example, secretory cells contain many elements of endoplasmic reticulum, Golgi apparatus, and vesicles; in the muscle, there are many myofibrils and mitochondria; nerve cells have nerve

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Fig. 10.2 Differentiation of genomes and their phenotypic framework. All cells of a multicellular individual have the same genome, originating from one mother cell—the zygote. However, an adult organism has more than two hundred phenotypically different cells. This wide variety of cells is based on differential expression of the genome. Different complexes of genes, different gene networks, “work” in different cells of different tissues and organs. As a result, in various tissues and organs of one organism, the structure of not only cells, but also their nuclei and genetic material looks different. This indicates a significant structural and functional reorganization of the genome in each case, which ensures the subsequent differential expression of proteins and the formation of a specialized phenome: 1—myelocyte, 2—fibroblast, 3—myocyte, 4—epithelial cell, 5—neuron, 6—optic cell, 7—sperm, 8—osteocyte, 9—odontoblast, 10—endothelial cell

processes, and so on. The arrangement of these organelles is strictly ordered in the cell in such a way that, for example, the muscle cell contracts in a certain direction, and the secretory cell secretes a substance only in a certain part of it. Undifferentiated stem cells have standard sets of organelles. 5. Differentiated cells often lose the ability to divide further, as exemplified by erythrocytes, muscle cells, nerve cells, and some others, whereas stem cells of various tissues can divide dozens of times. Mechanisms of differentiation. Differential gene expression. The hereditary material in the genome of all somatic cells of a multicellular organism is identical, despite their enormous phenotypic diversity. The genetic apparatus in the cells of all tissues is generally represented by the same diploid set of chromosomes, which completely retains the quantitative and qualitative composition of the genes, also characteristic of the primary zygote. Moreover, all genes retain the ability to manifest their activity,

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as has been proven by experiments on cloning organisms. This raises the question as to how genetically identical cells are able to form such a huge diversity. The answer to this question was found only at the beginning of the twentieth century, when the theory of differential (selective) gene expression in the process of individual development was substantiated experimentally. It postulates that at different stages of ontogenesis and at various times, different gene systems are expressed in the cells of different parts of the developing body. In particular, during embryonic cleavage, at different times, in different parts of an embryo, and in different stages, only those genes are active which are necessary at a given moment of development. Expression of these genes leads to the synthesis of a characteristic complex of proteins and the formation of certain features of a particular cell. For example, approximately 50 genes of body segmentation and a group of homeotic genes responsible for the detailed differentiation of each segment are involved in the formation of the anterior–posterior polarity of multicellular organisms. Having worked out their allotted time at a certain stage of development, these genes are blocked and never again manifest their activity, whereas others are turned on instead. For example, humans have approximately 25,000 structural genes. Of these, only a few thousand are differentially expressed in the cells of an adult organism, maintaining structural and functional homeostasis of cells and organs for the rest of its lifetime. Other structural genes are not used. Many of them were expressed in the development process, fulfilled their function, and subsequently remain further unsolicited. Expression of a gene into a trait is one of the main mechanisms of differentiation. Schematically, this process consists of several main stages: genome determination → differential expression of structural genes → formation of various mRNAs → synthesis of specific proteins → cell differentiation → performance of specific functions. The use of genetic information is a very complex, multistep process that is controlled by the genome in several stages: at the levels of transcription, translation, and expression. This means that the processes of differentiation of cells and tissues are also controlled at these levels. Differential gene expression continues in adult organisms. For example, a group of genes is expressed in hepatocytes that ensure the presence of proteins and enzymes specific only to their functions. Among them are genes for expression of blood albumin, glycogenesis enzymes, urea formation enzymes, etc. Muscle cells express a system of genes for various contractile proteins such as actin, myosin, troponin, and others. In this way, the specificity of the structure and functioning of all organs and tissues can be maintained over long periods. Genome differentiation. The genome of a multicellular organism is very flexible. For example, during the embryonic development of mammals, cells of the blastula, gastrula, ectoderm, mesoderm, endoderm, and then hundreds of varieties of tissue and organ cells are formed from the zygote by differential expression. This allows the formation of neurons, hepatocytes, fibroblasts, leukocytes, adipocytes, myocytes, and many others (see Fig. 10.2). In this case, it is not only the structure, shape, and size of cells that change greatly, but also the structural organization of the genome itself. Changes in the organization of the genome can even be assessed by the modifications in the morphology of the nuclei of differentiated cells, which is clearly visible under

10.5 Summary

273

a microscope (see Fig. 10.2). The morphology and appearance of chromatin changes, the ratio of eu- and heterochromatin changes, their localization changes, the shape and size of the nucleus change, and the nucleolar zones change their location, density, and size. These are visual changes, on the basis of which one can assess the highly complex molecular genetic rearrangements of the genome, such as the rearrangement and re-attachment of chromosomes, activation and deactivation of various regions of chromatin, changes in the qualitative and quantitative composition of enzymes, and other factors of transcription, processing, and splicing. That is, cell differentiation is associated not only with the selective expression of genetic networks, but also with a significant preliminary structural and functional rearrangement of the genetic material—genome differentiation. Therefore, the general expression scheme (see above) needs to be supplemented with one more stage: genome determination → genome differentiation → differential expression of structural genes → formation of various mRNAs → synthesis of specific proteins → cell differentiation → performance of specific functions. Thus, differentiation of cells and tissues, as well as their long-term functioning, are based on preliminary determination and subsequent differentiation of the genome. Consequently, it is the activity of the genome that determines not only the processes of reproduction, but also the totality of all processes of differentiation, growth, and development.

10.5 Summary The development of living bodies is a set of processes of successive irreversible clearly directed changes that lead to the emergence of new qualities. The definite patterns of development indicate that it is based not on random events, but on genetically determined processes. The determinism of these processes is associated with the material and informational essence of specific living bodies. In particular, development is controlled by genome programs as well as genetically controlled molecular and cellular interactions. Development processes are also influenced to a certain extent by environmental factors, within the range defined by the genome. In the course of the development of higher animals, there is a gradual differentiation of cells, tissues, and the whole body. This is preceded by determination and differentiation of the genome itself. As a result, the qualitative and quantitative changes in developing living bodies accumulate gradually, step by step, and this is accompanied by the accumulation of negentropy and information. The set of gradual modifications of genomes and cells determines the direction of the development of organisms and leads to the appearance of complete forms. The process of individual development is a unique genomic mechanism for the use of substances and energy to form living bodies. This mechanism serves to generate new sexually mature forms of multicellular organisms that produce gametes, and through their genomes transmit development programs to subsequent generations, providing the information needed for the material continuity of the planetary system of life. It is thus quite possible to assume that

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this system is indeed a kind of living organism, and living bodies are really just its structural units, performing two main tasks in order to maintain it. Firstly, organisms maintain integrity and homeostasis through reproduction. Secondly, living bodies are a mechanism for extracting and transforming matter and energy from the environment. It is the living bodies that organize and direct the chaotic thermal motion of matter towards their own temporary maintenance and the eternal maintenance of the system of life. With their deterioration and death, they pay off the laws of physics for the immortality of the phenomenon as a whole.

Part VII

The Inevitability of Death and the Mechanisms of Survival

Chapter 11

Life Expectancy, Aging, and Death of Living Bodies

After successful reproduction, living bodies have to exist in an active state for a certain, usually quite long period of time. This is necessary to be reasonably sure that reproduction will be successful. However, according to the laws of thermodynamics, all highly organized biological systems inevitably collapse over time. Their entropy is steadily increasing under the influence of internal factors, and in particular, the thermal motion of molecules and constant work (Chap. 7). In addition, living beings are also constantly exposed to adverse environmental factors. Thus, in order to survive, organisms need to constantly maintain their integrity, individuality, and homeostasis (see Chap. 12). They must constantly fight against internal factors of spontaneous dissipation, as well as against unfavorable environmental factors. But, despite this, the laws of physics are still stronger than the laws of biology. Therefore, notwithstanding their desperate resistance, living bodies still inevitably wear out, age, and die. But the most interesting thing is that, even despite the inevitability of natural death, nature also forcibly genetically limits the duration of life of each individuum. Moreover, life has no means and methods to struggle against this death sentence. The immortal genome leaves no chance for its phenotypic frameworks to exist longer than it wants. It should be noted that, when analyzing the problems of gerontology, scientists often consider (a) life expectancy, (b) aging, and (c) death as a single complex. This often very much confuses the situation when we try to understand the causes and essence of these phenomena. In fact, these phenomena differ in their essence and are not always connected with each other, as will be discussed in the rest of this monograph.

© Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_11

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11.1 Life Expectancy A certain lifespan is characteristic of all living systems. Nothing is eternal. Everything is destroyed according to the laws of physics. Everything material has a limited life. Entropy is merciless (see Sects. 2.4, 7.4, 8.4, and 11.2). This applies equally to cells, multicellular organisms, and even whole populations and species. Lifespan of unicellular organisms. There is a hypothesis that single-celled creatures that reproduce by division are immortal. It is observed that prokaryotes or unicellular eukaryotes, after division, do not leave a corpse behind, but simply turn into two new bodies. And if there is no corpse, then there was no death either. Daughter cells continue to divide, increasing their population, while there seems to be not a single dead body. Therefore, one really does get the impression that these unicellular beings have achieved immortality. But this is far from the case. First, even if the time between cell divisions is several hours or minutes, many of them still have time to wear out, get damaged, or even die, when faced with unfavorable environmental factors like toxins, radicals, mechanical influences, high or low temperatures and pressures, and all kinds of radiation. Therefore, in a colony of unicellular organisms, there will always be both dividing cells and cells that have lost the ability to divide, both living and dead bodies. Secondly, the mother cell still dies in the process of division, because it “breaks” in half and its mass disappears into the bodies of its daughter cells. Instead, cell division during reproduction should be considered as a variant of apoptosis (see Sect. 11.3.1). That is, the mother cell, having received a signal to divide, actually receives a command to self-destruct. Hence, all singlecelled creatures are mortal. The causes of their death are damage, wear, and division. And their lifespan, necessarily limited under these conditions, is determined by the length of time from one division to another, which is genetically regulated by the genome. In this whole life story, only the genome demonstrates its immortality, by constantly changing its phenotypic framework to a new one. Lifespan of colonies. Prokaryotes and many other unicellular organisms usually live in colonies. The lifetime of such a system is much longer than the life of its individual members. For bacterial cells, the lifetime between divisions in a colony can be 20–30 min. For ciliates, for example, the genus Tokophrya, the lifespan is several days, and with a lack of nutrition, several months. Colonies of slime molds, some imperfect fungi, and some algae live up to 10–20 years, although the maximum lifespan of an individual member of the colony is about one year. The duration of reproduction by division for each colonial species of living bodies is determined and limited. While some species can reproduce for several days, others can exist in culture for several months and give several hundred generations. But all the same, most populations become smaller; their members stop feeding and multiplying, degenerate, and die. The death of unicellular organisms is also associated with their asymmetric division, when, in the process of division, the contents of the mother cell are unevenly distributed to daughter cells. As a result, one of the two daughter cells retains the stem qualities of the mother cell, and the second turns out to be functionally active, but less viable and less reproductive. Over time, the number of these aging cells increases

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critically, and this leads to the aging and death of the colony. However, in nature there are some other colonies of living beings that live almost indefinitely. Their remarkable viability is most likely based on high resistance to unfavorable factors, equivalent symmetrical division of the mother cell, and a high rate of replacement of old cells by new ones. Similar considerations apply to cell cultures grown artificially by scientists in the laboratory. Some cell or tissue cultures can exist for only a limited period of time due to the presence of the Hayflick limit for each dividing cell, while others, for example, derived from malignant tumors or artificially immortalized using gene technology methods, can proliferate virtually indefinitely (years). But in any case, with a longterm culture under the influence of various factors, the properties of many cells change. The signs of modifications are violations of the morphology of cells, a change in the number of chromosomes, a decrease in functionality, etc. After a certain period of time, the cellular units of the composition of the colonies nevertheless inevitably die. Thus, the long-term existence of colonies in no way implies their immortality or the immortality of their constituent living bodies. The relatively long-term existence of colonies or cell cultures is based on genome-regulated division of units of the system and the corresponding rate of replacement of old cells. Once again, we note that the main character in all the dramatic events of “division death” is the genome, which imperceptibly guides its own translocation into new living bodies. Lifespan of cells of multicellular organisms. Mammalian organisms are composed of a vast number of cells that form various tissues and organs. Cells in different structures and with different functions can live from several hours to many years. For example, epithelial cells of the human small intestine live for about 36 h, cells of the epidermis of the cheeks for 10 days, liver cells for 450 days, hematopoietic stem cells for 5 years, fat cells for 8 years, and heart muscle cells for 40 years. However, the average life expectancy of a human is noticeably longer, reaching over 70 years. This is significantly longer than the lifespan of most of its constituent cells. Therefore, the normal organization and functions of tissues and organs is maintained via the constant replacement of worn out and dead cells by new ones of the corresponding type and state of differentiation. In the process of functioning, these in turn wear out, age, and then die. Their place is once again taken by other cells that appeared after the division of the stem and committed precursors. That is, organisms have the ability to restore and maintain cellular composition, thereby ensuring the integrity and longer life of individuals. Since different cells have different maximum lifespans, even though they have the same genome, it is obvious that the genome can also regulate it. First of all, the lifespan of variously differentiated cells depends on their structural and functional purpose. In long-lived cells, the genetic programs of self-repair most likely last much longer. Moreover, many cells have genetic programs for timely self-destruction (for example, apoptosis), which are triggered in the event of infection, wear, damage, specific signals, or genetic degeneration. This is a gene system that can trigger a selfdestruction mechanism in the event of lethal damage or at the first sign of uncontrolled division.

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Nucleic acids and proteins, the main macromolecules in cells, also have a limited lifespan. DNA molecules are fairly stable, long-lived molecules with their own repair system. They have the ability to replicate, which makes them potentially immortal. RNA molecules are short-lived intermediary molecules involved in protein synthesis. Their quantitative and qualitative composition is updated rather quickly. Proteins are the main molecules that directly provide the structure of living bodies and all life processes. Proteins wear out rather quickly as a result of use, the thermal motions of surrounding molecules, chemically active substances, toxins, radicals, etc. Most of the structural proteins of cells exist for several days. Certain other proteins degrade within a few minutes after their synthesis. These proteins include many enzymes, whose synthesis is regulated by the genome in accordance with metabolic demands. There are short-lived proteins and peptides with a lifetime of seconds. Some proteins are long-lived, such as histones, which are involved in the spatial folding of DNA. On average, the lifespan of cellular proteins is several hours. The ability of cells to live much longer than their proteins is due to the constant resynthesis of degraded proteins and the restoration of protein homeostasis. The absence of any of the proteins, errors in their synthesis, as well as wear and degradation lead to the dysfunction and death of cells. Consequently, the stability of the qualitative and quantitative composition of proteins, which is controlled by the genome, can significantly affect the lifespan of cells. Genetically determined lifespan of organisms. Millions of different biological species of living beings live on the planet. The maximum lifespan of any individuum is limited (Table 11.1). Each representative of a certain species has a genetically programmed maximum lifespan, to which only a few organisms survive. For example, the maximum lifespan for a rat is 5 years, for a dog 20 years, for a chimpanzee 60 years, for an Indian elephant 85 years, a human 120 years, a Greenland shark around 500 years, some individual plants can live for thousands of years. The overwhelming majority of individuals do not live to this age due to premature death or disease. However, it is still unknown what genetic mechanism determines the lifespan of an individuum. Why some turtles can live more than 150 years, and lizards only live up to 10 years; why swans live up to 70, and pigeons up to 35 years. Why do cats live up to 30, and humans up to 120? Why can a queen bee live up to 5 years, while worker bees (with the same genome) live only 40 days in summer and 90 days in winter? Why do cells of different tissues and organs of a human live for different times, from several days to tens of years? The data on the life expectancy of representatives of different species prompt the following remarks: (a) there is no clear relationship between the life expectancy and taxonomy, although more highly organized species tend to live longer; (b) the lifespan, even among closely related species, can vary greatly; (c) larger species of animals live longer than small ones, although there are exceptions; (d) each species has its own inherited life expectancy; (e) in some animals, the lifespan of an individuum depends on the season (bees); (f) in some insects, larvae live much longer than adults (Fig. 11.3); (g) individuals of the same species, but of different sex and biosocial status (for example, queen bees, worker bees, and drones) may differ

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Table 11.1 Average and maximum lifespan of some animals Name of the organism

Life expectancy

Maximum lifespan

Mayflies, imago (Ephemeroptera)

1–3 days

20 days

European honey bee (Ápis melliféra): Queen bee worker bee

3 40 days (in summer)

5 9 months (in winter)

European crayfish (Astacus astacus)

5 years

20 years

Freshwater pearl mussel (Margaritifera margaritifera)

10–15 years

100 years

European medicinal leech (Hirudo medicinalis)

4–5 years

20 years

Greenland shark (Somniosus microcephalus)

–

500 years

Wels catfish (Silurus glanis)

40 years

100 years

Aldabra giant tortoise (Aldabrachelys gigantea)

40–50 years

150 years

Common European viper (Vipera berus)

5 years

25 years

Common pigeon (Columba livia)

6 years

10 years

Common raven (Corvus corax)

20 years

100 years

Human (Homo sapiens)

70–80 years

120 years

Chimpanzee (Pan troglodytes)

50–60 years

75 years

Dog (Canis lupus familiaris)

10–12 years

20 years

Asian elephant (Elephas maximus)

60 years

85 years

Horse (Equus ferus caballus)

20 years

62 years

significantly in life expectancy, although they have the same genome (Fig. 11.1); (h) organisms growing throughout life usually live longer than organisms with limited growth; (i) poikilothermic animals live longer than homoiothermic ones. It is difficult to find a consistent pattern in the above observations, but the facts listed above suggest the presence of a stable internal determination of the duration of the life of all living bodies. The following facts testify in favor of a genetic determination of the lifespan of organisms: (a) life expectancy is an inherited constant characteristic trait of a given species; (b) generally, the lifespan of identical twins is very close, whereas fraternal twins do not exhibit such a correlation; (c) some known hereditary diseases bring accelerated aging and death in humans (progeria, associated with a violation of the DNA repair process); (d) breeds of animals were developed by means of hybridization, and their lifespans often differ from those of the parents; (e) generally, the longer parents live, the longer their descendants live. A well-studied example of genetically induced programmed cell death is apoptosis (Fig. 11.5). By analogy with the phenomenon of apoptosis, the existence of a genome-programmed mechanism for the destruction of multicellular organisms can be assumed. Such a mechanism could play role in cleansing the population of

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Fig. 11.1 Different phenotypic framework of one genome (Apis mellifera). Different social groups of bees not only look different, but also live for different lengths of time. The queen lives up to 5 years, the drone for several days (it dies immediately after inseminating the queen), and worker bees live up to 40 days in summer, and up to 9 months in winter. Image adapted from G.F. Taranov: “Biology of the bee colony”, Moscow (1961)

worn-out, hazardous, or useless individuals. This process is referred to as phenoptosis. It is assumed that the human population is also regulated by the instruments of phenoptosis, when unfavorable environmental factors and various kinds of stress provoke heart attacks, strokes, carcinogenesis, and suicides, the likelihood of which increases with aging. Semelparous species that reproduce only once in their life and rapidly die soon after that, as a result of the inclusion of self-destruction programs (salmon, eel, annual and biennial plants), are also an example of phenoptosis. Thus, in addition to natural forms of destruction from constant work, wear, and manifold unfavorable external impacts, Nature has in addition strictly limited the lifespan of individuals genetically. Apparently, the inevitability of the death of individual living bodies and the change of generations are crucial for the adaptation and evolution of species of genomes and renewal of the planetary system of life to ensure the immortality of the phenomenon of life. Lifespan of genomes. The genomes of cells and organisms that reproduce by asexual mitotic division (prokaryotes) are replicated and enter the next generation of living bodies unchanged. That is, such genomes are basically immortal. The genomes of eukaryotic individuals that reproduce sexually live in their phenotypic framework for the same period of time and die along with their carrier body. Yet, in the case of successful reproduction, there is a “reincarnation” of the genome (see Chap. 9), but with a slightly altered allelic composition. The updated genome builds a standard phenotypic framework, with certain peculiarities, where it continues to exist. This can continue countless times, suggesting the potential immortality of eukaryotic genomes as well (see Sect. 18.3). Very interesting transformations of genomes and their bodies occur during the metamorphoses of insects. For example, the development of the May beetle (Melolontha melolontha) (Fig. 11.2) includes several fundamentally different stages: (1) Fertilized eggs develop for 2 months and turn into larvae. (2) The larvae live and

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283

Fig. 11.2 “Life cycle” of the May beetle and its genome. The figure clearly demonstrates that, in fact, the life of an individual is not cyclic, but finite—the imago will inevitably die. But the life of the Melolontha melolontha genome is indeed cyclic. The transport forms of the genomes (gametes) are combined in the process of sexual reproduction to form new carrier bodies. During this cycle, the same genome lives in different living bodies, and then through the transit form of germ cells, with some recombinations, it moves into the body of a new individual

develop for 3–4 years underground and pupate. (3) The larvae die in the pupae (a type of phenoptosis) and disappear as a result of the disintegration of their bodies down to the monomers of macromolecules. A group of pupal stem cells uses the larva’s matter and transforms it into the bodies of adults, which spend half a year, from October to April, hibernating underground. (4) In May, adult organisms appear on the surface of the earth. Their genome has a completely different body compared to all previous stages of development. And for only one month, in May, imago adults of May beetles live freely, feeding, flying, and mating. (5) As a result of fertilization, the haploid genomes of gametes unite and form the diploid genome of a new organism with a different allelic composition, which develops inside the fertilized egg. The next round in the endless circulation of the Melolontha melolontha genome begins. In all these stages of development, a representative of the biological species of Melolontha melolontha contains the same genome, yet manifesting itself as completely different living organisms. That is, at each stage of the life cycle, the individual genome is reprogrammed and selectively expressed, producing completely different living bodies with certain periods of existence. Thus, the total lifespan of individuals of the May beetle and their genomes is determined by the sum of the duration of all their stages of development. Consequently, the true duration of their individual lives is 4–5 years, and not one month of existence at the imago stage. At the same time, the lifespan of a species of the Melolontha melolontha genome is nearly unlimited, since the order of insect beetles (order Coleoptera) have existed on Earth for hundreds of millions of years. In the continuous process of reproduction, their genomes move to other habitats and continue their endless path. That is, neither the death of cells, as the nearest phenotypic framework of genomes, nor the death of an individual, as a formed colony of genomes, stop the process of

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Fig. 11.3 The rise and fall of the orderliness of animal organisms in the process of ontogeny. Fertilization gives the impetus for an explosive process of deterministic self-organization. A high level of orderliness and organization is noted at the moment of birth of a living body, reaching a maximum towards puberty. At the first stages of life, cells are able to divide very quickly, selfrenewing and renewing the body. Despite the action of damaging factors, the body remains young and healthy if the cells are renewed faster than the rate of accumulation of damage. At a young age, the processes of protein synthesis and the formation of new cells prevail over the processes of damage and wear, so the body grows and develops. In adult organisms, equilibrium is established for a certain time. However, in an aged organism, the processes of destruction of the ordered structures of most cells and more complex systems prevail over anabolic processes, and this leads to an imbalance in nearly all functional systems. This means that, from a certain time, the renewal processes slow down (due to termination of the supporting genetic programs), damage accumulates in the body (entropy increases), and this leads in the end to a natural finale—the body dies. The renewal of genetic programs for the development and maintenance of integrity is possible only after genomes are “reset” in the process of reproduction

cyclic reincarnation of genomes even for a second. This is the basis for the perpetuity of planetary system of life and the permanence of the phenomenon of life. The lifespan of biological species. Numerous species of organisms, or rather, species of genomes (see Sect. 18.3), inhabit the Earth for long periods of time, yet not forever. The average lifespan of a species can be several million years, despite the significantly shorter lifespan of its constituent individuals. For example, many modern species of insects, in particular ants, dragonflies, cockroaches, etc., have been living on Earth for tens of millions of years, and for certain species of crustaceans, brachiopods, and reptiles, the age is known to be hundreds of millions of years! The basis for the long existence of genomic species is the ability of individuals to transmit stable genetic information practically unchanged to subsequent generations thanks to their ability to reproduce. The death and extinction of species are often caused by planetary catastrophes, the evolution of the Earth, changes in habitat, or competition. This can significantly limit the ability of individuals to survive and reproduce. As a result, the genetic

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285

continuity of the species is cut off. In particular, over billions of years of evolution on our planet, significantly more species of living organisms have perished than exist now. Among the best known examples are dinosaurs, pterodactyls, and mammoths. It seems likely that the lifespan of biological species is also genetically determined. This can be evidenced, for example, by the sudden (within several thousand years) extinction of dinosaurs that reigned on Earth for hundreds of millions of years. Since the whole taxa, and most importantly, their genomes, disappear from the face of the Earth, this process of programmed death of species can be designated as genoptosis (by analogy with apoptosis and phenoptosis). How can this happen and what could be the reason? It has now been established that genomes contain many segments with unknown functions, many of which are descendants of viruses, bacteria, and mobile genetic elements. All of them can be activated at any time with unpredictable consequences. The risk to the stable existence of genomes is also augmented by continuous genetic transmission within the global genome, with both vertical and horizontal transfer of genes. That is, there is a constant shuffling of genes within the global genome system which results in the generation of all kinds of combinations, and from time to time a certain species of genome gets a fatal one. Thus, the lifespan of cells, living bodies, and biological species is limited by the laws of thermodynamics and it is also predetermined genetically, so it is not always associated with aging. It is only an active opposition to increasing entropy that allows organisms and species to exist, and even then, only within the time allotted by the genome.

11.2 Aging As already noted, the main reason for the inevitable death of living bodies is the laws of nature. Under the physical conditions that support life, biological systems must collapse under the influence of the thermal motion of molecules and constant work. Therefore, during the permanent struggle with entropy, organisms wear out, that is, they age. To stop aging, one has to stop moving and stop working. However, it is physically impossible to stop this motion, and ending the struggle against entropy leads to instant death. Living bodies exist for a limited period only, based on self-reparation of decaying structures through the consumption and purposive use of free energy and matter from the external environment. Consequently, the duration and accuracy of the functioning of the processes that support life determine the duration of life of any given biosystem (see Sect. 11.3). Aging is a deterioration of organisms associated with the action of unfavorable factors along with violation of genetic self-repair programs, manifested in a violation of properties and functionality and a decrease in the viability of organisms. Aging is an invariable attribute of most living bodies, which appears at their birth, that is, at the moment of fertilization. During intensive growth and development, aging remains

286 Table 11.2 The main causes of the death of living bodies

11 Life Expectancy, Aging, and Death of Living Bodies External

Internal

Geophysical and ecological disasters

Aging of organisms

Mechanical injury

Aging of stem cells

Freezing

Internal illnesses

Overheating

Termination of cell proliferation

Predation

Terminal cell differentiation

Hunger

Cell division

Thirst

Reaching the Hayflick limit

Poisoning

Malignant degeneration

Irradiation

Metamorphosis Apoptosis Phenoptosis

practically unmanifested. Signs of aging usually begin immediately after puberty. Every year such signs deepen and new ones appear. Aging ends in death. However, it should be noted that aging is only one of the numerous causes of death (Table 11.2). The aging process is characteristic of all levels of organization of organisms, from molecules to functional systems. Cellular aging. Aging of cells is molecular in nature. Most of the functional molecules found in the colloidal solution of the cytoplasm change over time, mainly as a result of interaction with other molecules and atoms (thermal motion, chemical reactions, free radicals) and under the influence of electromagnetic radiation (ultraviolet light, radiation). Molecules can disintegrate into atoms, transform into other molecules, undergo structural changes, and undergo denaturation. In such circumstances, the efficiency of performance of functions by biological systems can alter significantly. A powerful factor and mechanism of cell wear is the non-stop thermal and Brownian motion of molecules. The average speed of motion of molecules at physiological temperatures is useful and necessary for the implementation of a whole range of different chemical and biophysical processes. But many molecules have excess speed and excess energy of motion, which can gradually lead to denaturation of biological molecules when they collide. Some molecules have colossal energy and can immediately disable a biological structure by their impact. Water molecules also have a significant destructive effect on macromolecules, since some of them have very high speeds and so can easily interact with other molecules. But these pathological processes are opposed by cellular recovery mechanisms (see Chap. 12). The same biological macromolecules and ultrastructures can be formed and restored simultaneously with the noted disturbances. However, over time, the rate of recovery begins to lag behind the rate of destruction, thus causing the gradual wear of cells. At the

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287

same time, this period begins at very different junctures in different species and can vary over many orders of magnitude, depending solely on the genomic program of a given species. Constant work also has a significant impact on the wear and tear of cells and organisms. It should be realized that every biochemical reaction and every biophysical or physiological process involves a vast amount of work associated with the exchange of energy between bodies during their interaction or with the transfer of mass or energy over a distance. Billions of different molecules and many cell structures are involved in physicochemical and physiological processes. For example, the metabolism of a cell is provided for by trillions of enzyme molecules, thousands of ribosomes, hundreds of mitochondria and lysosomes, large amounts of Golgi apparatus, endoplasmic reticulum, and more. Enzymes and ribosomes are constantly working, intricate, high-precision molecular machines. And like all operating machines, they gradually wear out. This also applies to the macrostructures of cells, such as mitochondria, which are composed of highly complex structural and functional macromolecular blocks, constantly working and transforming matter and energy (see Sect. 7.3). Moreover, the cells of organisms spend around 90% of the energy they obtain on the task of self-repair. So only 10% of the energy is spent on work to ensure the cell’s specific functions within the organism. Among the essential factors causing molecular damage in living cells are superoxide oxygen radicals, which are highly reactive molecules with an unpaired electron. They are formed as by-products in the processes of energy conversion in the respiratory chain of mitochondria, as well as in a number of other metabolic reactions. These molecules are highly reactive and can attack and damage a wide variety of organic molecules, including nucleic acids and proteins. An example of another dangerous molecular factor is the nonspecific interaction of cellular macromolecules with glucose (glycosylation). The factors of aging also include various mechanical, osmotic, electrical, and other processes, as well as various kinds of radiation and waves. These and a number of other effects can cause damage to the lipids in cell membranes, inactivation of enzyme proteins, glycosylation of structural proteins and the formation of cross-links between them, DNA damage, gene mutations, and more. This, in turn, leads to a gradual destruction of the structure and deterioration of functioning cells. The integrity and permeability of membranes is violated, enzymatic activity decreases, the cell becomes clogged with metabolic products, and protein synthesis and regulation of cellular processes are disrupted. In addition, due to the deterioration in the functioning of cells and the death of some of them, regulatory processes are disrupted at the intercellular and organismal levels, and as a result of feedback, this leads to a further increase in damaging effects at the molecular level. All this contributes to a catastrophic dysregulation of metabolism and functions, the emergence of systemic diseases associated with aging (most forms of cancer, atherosclerosis, hypertension, diabetes mellitus), and a weakening of the body’s resistance to stress, all of which in the end leads to senility and death. Cells possess a range of “anti-aging” mechanisms able to resist damaging environmental factors. A good example is the conversion of superoxide oxygen radicals into

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hydrogen peroxide, carried out by the very ancient enzyme superoxide dismutase, which is then split by catalase into water and molecular oxygen. Other examples are groups of enzymes that restore damaged regions of nucleic acid molecules (nucleases, polymerases, ligases), degrade damaged proteins (proteinases and peptidases), and restore denatured proteins after the action of stress factors (chaperones). Cells are constantly removing damaged molecules and toxins, as well as synthesizing new molecules. Non-lethal damage to membranes and organelles can be restored, and the coherence of metabolic processes is constantly maintained. Cytoplasmic segregation of disturbed structures and waste products and their isolation during asymmetric division can take place during mitosis. These mechanisms of self-repair significantly slow down the processes liable to deteriorate cellular structures and the aging process itself, but they cannot stop it. It should be noted that aging is a very complex phenomenon that includes many of the listed processes of violation of homeostasis and maintenance of integrity. Most likely, there is no specific aging gene or special genetic aging program. At the same time, Sect. 11.1 and Table 11.1 clearly indicate that there is a genome program that limits the maximum lifespan of its phenotypic framework. This could be done by disabling or changing the mechanisms of self-restoration. There may be thousands of such mechanisms, for example, blocking the synthesis of one of the key metabolic enzymes, blocking proliferation by limiting the synthesis of telomerase, or blocking the synthesis of carrier proteins of biological membranes, and many others. In different cells and in different organisms, these mechanisms of programmed blockages or disorders may be completely different, acting in different combinations and at different times. This is most likely the reason behind the different periods and different patterns of aging in different taxonomic groups of living bodies. So, understanding the role of just one of the mechanisms (for example, the telomerase gene) and manipulating that is unlikely to solve the problem of aging in principle. The molecular and cellular signs of aging are manifold. For example, in the somatic cells of an aging organism, up to half of the rRNA genes are inactivated, and while certain mRNAs are observed to disappear, some other mRNAs are observed to appear. The content of non-histone proteins in chromatin decreases with age and their bonds with DNA become less labile. Therefore, as it ages, the cell uses partially changed genetic information at different junctures. This leads to a gradual change in the qualitative and quantitative set of proteins formed in the cells, and in particular, various enzymes, which constitute the basis for anabolic processes and maintenance of integrity. Aging can be caused by disturbances in gene expression as a result of somatic mutations. Changes in genes can shift the ratio of synthesis of different proteins, to a decrease in the potential of protein-synthesizing systems, to a lack of synthesis, or to the formation of defective proteins. This disrupts the metabolism and functions of cells, and limits their reparative and adaptive capabilities. For example, the activity of enzymes responsible for oxidation decreases in an aging body. This leads to a deterioration in the transformation of energy, which is also associated with a decrease in the number of mitochondria in cells. One specific peculiarity of an aging organism is a shift in the ratio between tissue respiration and glycolysis in the energy supply

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289

process in favor of an ineffective anoxic pathway of ATP formation. Aging affects almost all organelles, both general and specific. The age-related rearrangements are most noticeable in permanent highly specialized cells, such as neurons and cardiomyocytes. Aging nerve cells, for example, are characterized by a depletion of membrane structures in the cytoplasm, a decrease in the volume of the rough endoplasmic reticulum, and an increase in the content of microfibrils which can disrupt the transport of substances along nerve the processes. Simultaneously, there can be an accumulation of unusual substances, sometimes structurally formed (lipofuscin), cluttering the cell and changing its functions. This is accompanied by a slowdown in the conduction of nerve impulses, and in some types of nerve cells, a decrease in the amount of the relevant mediator. Aging of multicellular organisms. It is known that in nature, destruction occurs “all by itself”, while creation requires the expenditure of energy. Living organisms actively resist the growth of entropy, spending the matter and energy they transform. Moreover, they can even form increasingly complex structures and accumulate information and negentropy in the form of orderliness and functionality. These processes are opposite to destruction and aging. For example, immediately after fertilization, the orderliness and complexity of the embryo increases dramatically: the number of cells grows rapidly; cells differentiate and separate; and tissues, organs, and body parts are formed (see Chap. 10). The creation of orderliness occurs on the basis of the genetic program of development, and then orderliness is maintained throughout the entire period of existence. The highest degree of order in most animals is created by the time they reach puberty (Fig. 11.3). Upon completion of growth and the beginning of reproduction, genetic programs for development and maintenance of integrity are terminated or changed, probably as a result of blocking a certain part of the genome by some regulatory factors, indicating readiness for reproduction. As a result, nature abandons a mature organism, leaving it alone to face the second law of thermodynamics. After that, the level of orderliness of living bodies begins to gradually decrease. This causes natural wear and aging of cells, tissues, and organs. Further, the reproduction process is naturally disrupted, and then ends. Afterwards, regulatory processes are disrupted, resistance decreases, and pathologies and diseases accumulate. In a decrepit organism, the probability of death increases progressively. After death, the disordering process is completed as a result of the disintegration of an organism into its constituent molecules. Once again, we note that, due to the multifactorial nature of the causes and effects of wear on cells and organisms, it is logical to assume that there is no special genetic aging program or aging gene in the genomes of multicellular organisms. Wear is most likely associated with the termination or disruption of self-recovery programs, which invariably leads to aging and death. The strategically successful struggle of life with entropy is possible only due to the existence of a genetic reproduction program which is repeatedly rewritten and transmitted to subsequent generations through the mechanisms of DNA replication and transcription. A living organism with a genome can be compared to a book that is constantly being reprinted. The paper (phenotypic framework) on which the book

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is written can wear out and decay, but its publication is eternal if the matrix (genome) for its creation and content is preserved. Progeria demonstrates the importance of restorative processes. This is a human genetic disease which manifests itself in the very rapid aging of an individual. Patients with progeria already look like decrepit old people in childhood and live on average only 10–13 years. It turns out that this is due to a violation of the repair process of DNA molecules. The telomerase aging hypothesis is also related to a violation of one of the restorative mechanisms for maintaining the integrity of a living system. Telomerase is an enzyme that maintains the constant length of the ends of a linear chromosome, and thereby preserves it from gradual destruction. Cessation of the work of telomerase is associated with cessation of its formation, and therefore, with cessation of the genetic program for reproducing it. In addition, the work of telomerase is associated with the regulation of the number of divisions (that is, the lifespan of cell populations), but not with the fight against molecular aging of the cells themselves. Consequently, the telomerase mechanism of impaired cell reproduction can be only one of the reasons for the imbalance and aging of a multicellular organism, but not of individual cells. The telomerase mechanism can explain the different lifespans of groups of cells (determining the moment of their death), but it is not the cause of their aging, although it may be one of the reasons for the aging of a multicellular organism. Aging can also be considered as a gradual heterogeneous disruption of differential gene expression in living organisms. On the basis of such discoordination, many metabolic processes are disrupted, and “unauthorized” spontaneous biochemical reactions that are not controlled by cells and the body begin to appear more and more often. Disintegration of cell metabolism, organ dysfunctions, and an imbalance in the finely tuned system of the organism as a whole result in the appearance and manifestation of a number of gerontological diseases. According to Medawar’s hypothesis, senile extinction is the result of the accumulation in the gene pool of lethal and semi-lethal genes acting in the late stages, which have managed to pass through the networks of natural selection only because their effect manifests itself at a later age. On the other hand, in any organ of an aging organism, changes typical of this process are combined with adaptive modifications aimed at counteracting structural and functional disorders. In particular, hormonal, immune, and neuroregulatory compensatory processes are actively involved in the correction of aging processes. The body also contains cytogenetic and molecular mechanisms that inhibit aging and promote survival. In particular, these are: (a) replicative regeneration of DNA and the genome itself via mitosis of body cells; (b) cytoplasmic segregation of maladies and toxins, asymmetric cell division and the ensuing removal of defective cells by apoptosis and subsequent phagocytosis; (c) metabolic maintenance of integrity and homeostasis; (d) activity of the antioxidant system; (e) continuous regeneration and reproduction of cells, as well as cellular components; (f) enzymatic control of the integrity of DNA and proteins; (g) formation of new genomes of gametes, fertilization, and the formation of a revived diploid genome.

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291

All the structures and functions of the body are involved in the aging process. An important feature of this process is selectivity and heterogeneity. In accordance with this, changes characteristic of aging appear in various cells, tissues, and organs at different periods in the aging process. This is primarily due to the specificity and intensity of metabolism and functions, as well as to the different recovery abilities of the various biological systems. It should be borne in mind that the aging of a multicellular organism, as a colony of cells of the same genome, and the cells themselves, as individual members of such a colony, are completely different processes. Cells are autonomous microheterogeneous molecular systems, whereas multicellular organisms are macrosystems built from a multitude of these autonomous microheterogeneous systems. For individual cells, the decisive factors of aging and death are thermal motion, physicochemical work, radicals, and other molecular processes, while the cause of aging and death in a multicellular organism is, in addition, the accumulation of disorders in the systems for supplying and managing groups of cells, body parts, and functional systems. In particular, with age, the work of the central nervous system, endocrine, and immune systems is violated. In addition, all structural and functional systems of animals, including the cardiovascular, musculoskeletal, digestive, and other systems, are worn out through constant work. Importantly, the aging rate, both in the first and in the second case, is determined by the efficiency of the mechanisms for maintaining integrity and homeostasis, defined by the genome. The total result of the numerous manifestations of aging at the level of the whole organism is the violation of its properties that contribute to survival and reproduction, as well as a gradual decrease in the functionality and viability of the individual and a decrease in the efficiency of adaptive and homeostatic mechanisms. Apparently, nature has deliberately limited the lifespan of individuals at the genetic level to ensure the inevitability of their death, an important mechanism for the constant renewal of generations of living bodies, something that is crucial for adaptation and evolution. This is done, most likely, via the purposeful turning off of “supportive” genetic self-repair programs (Fig. 11.4). As a result, living bodies simply wear out due to the action of a multitude of unfavorable factors. An organism, although it has a wide margin of durability and the ability to repair itself, is nevertheless gradually destroyed at all levels. This is the natural aging process. There is no need for special programs or aging genes, and no additional efforts are required, because, according to the laws of thermodynamics, the destruction of organized systems occurs spontaneously. This turning off of the complex of genes that control the processes of development and the maintenance of integrity and homeostasis, along with the turning on of the genetic program of phenoptosis, occurs in different individuals in different time frames and in a different order, thus determining the interspecific and intraspecific scatter of life expectancies. The expediency of aging and subsequent death is a universal way of removing individual living bodies, as they are incapable of evolution. In general, aging leads to a progressive increase in the likelihood of death and inevitable death of an

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Fig. 11.4 Forced creation—maintenance and spontaneous destruction of cells and living bodies. 1—The beginning of the life of an organism at the moment of emergence; initiation of genetic programs for development and maintenance. 2—Shutdown of development programs. 3—Violation or interruption of integrity maintenance programs; spontaneous aging and destruction of the body. The aging process is a very intricate and complex trait. It covers all levels of organization of the living, including all cells, organs, and systems. That is, the aging process and lifespan are determined by a complex of different genes. This implies the presence in the genome of a certain genetic program of ontogenesis that includes the processes of development and maintenance of integrity, as well as the moment of their completion

Fig. 11.5 Cellular demolition pathways. (1) Demolition of a dead cell—necrosis. (2) Demolition of a cell that is defective or has fulfilled its functions—apoptosis

organism. This is extremely important, as it ensures the renewal of generations and the appearance of improved genomes capable of evolution. Do genomes themselves age? Of course, since they are highly organized living systems, which, like all life on Earth, obey the laws of physics. In particular, thermal

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293

motion, tireless work, superoxide radicals, toxins, and many other harmful factors lead to mutations, replication, and transcription errors, which can have disastrous consequences for cells and multicellular bodies. However, the genome also has its own security system, for example, in the form of a number of replication enzymes capable of correcting some DNA mutations. Yet, the genome is not able to fight forever against the laws of physics. Therefore, it can also gradually accumulate damage, wear out, and lose the ability to perform its duties. As the permanent successful fight against ruthless entropy is beyond its control and ability, it is more convenient for the genome to start all over again—to reproduce itself in a renewed version and move into a new body. Along with this, the genome is absolutely indifferent to the fate of its temporary phenotypic framework, which it regularly changes. Hence, all living bodies always appear, develop, multiply, age, and die, and will continue to do so forever. Aging is one of the reasons for their inevitable death (Table 11.2). But their genomes do not disappear without a trace if organisms leave behind offspring carrying a slightly altered immortal genome. This means that the phenomenon of life, whose essence is the global genome, is not subject to aging or death, but rather to endless evolution. As one of the properties of Nature, this phenomenon will exist on Earth as long as there are suitable geophysical conditions for genomes and their carriers to inhabit the planet, hence for a few more billion years. In contrast, the aging and the limited duration of life of individual organisms, which are just “disposable bodies”, does not much matter, either for their genomes or for the immortal planetary system of life.

11.3 Death The inevitability of death. A certain life path is inherent in every type of organism. For example, in animals at the initial stages of ontogenesis, the organism grows and develops. This is followed by a period of puberty and reproduction. The body then ages and eventually dies. Thus, death is the natural end result of the ontogenesis of any individuum. Death occurs from the moment of the irreversible cessation of the main processes and functions that support life. This is a hereditary trait in the life of every cell or organism, and it is an inevitable natural event after a certain period of time. The features and duration of ontogenesis for representatives of different species of organisms vary significantly. Some live for only a few days, while others live for hundreds of years. The maximum lifespan is a genetically fixed phenotypic trait. No one has yet managed to outwit ruthless nature and achieve immortality. There are many causes of death of living bodies. Generally, the laws of physics determine the inevitability of their death (see Sects. 7.4, 11.1, and 11.2). All cells and organisms are doomed to die from the point of view of the laws of thermodynamics, since the long existence of highly organized heterogeneous nonequilibrium systems is impossible. They are doomed to collapse and turn into a homogeneous mass. Yet,

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although they gradually wear out, they can still exist for a limited period, thanks to artificial restoration using the influx of free energy and matter from the external environment and the constant work put in by every living system to fight against entropy and maintain its integrity (Fig. 11.4). In addition, as noted above, all representatives of all biological species have a genetically determined maximum lifespan. It seems that the enormously wide spread of the maximum life expectancy in representatives of different species, from several days to hundreds of years, can be explained by the specifics of the organization and operation of the supporting genetic programs of the genome, as well as by the different timings and orders of their shutdown. Moreover, whatever this period may be, from minutes to centuries, it is sufficient for the complete reproduction of genomes and their phenotypic frameworks. However, despite being doomed and having to face the colossal difficulties of existence in a living form, organisms still successfully live on their home planet for a period determined by the genome or by fate. But in the end, all living organisms are equal in the face of their inevitable demise. The main causes of the death of organisms can be conditionally divided into internal and external (Table 11.2). We can also subdivide the causes of death depending on genetic or non-genetic factors, or indeed biological and physicochemical factors (Table 11.3). At the same time, it should be noted that the processes involved in the death of cells and multicellular organisms have their own inherent peculiarities. Table 11.3 Genetic and non-genetic causes of the death of living bodies Genetically determined causes of death as a result of termination of genetic programs maintaining homeostasis, functionality, and integrity

Genetically determined Biological causes of causes of death through death. Premature, not implementation of genetically determined special “killing” cytogenetic programs

Physicochemical causes of death. Premature and accidental

Aging of organisms

Terminal cell differentiation

Infections

Geophysical and ecological disasters

Aging of stem cells

Cell division

Internal illnesses

Mechanical injury

Termination of cell proliferation

Malignant degeneration Hunger

Freezing

Reaching the Hayflick limit

Metamorphosis

Thirst

Overheating

Apoptosis

Predation

Poisoning

Phenoptosis

Irradiation

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11.3.1 Death of Cells (A) Genetically determined causes of death by stopping genetic programs that support self-repair, integrity, and functionality (Table 11.3). “Slow killing” The natural death of long-lived cells (neurons, cardiomyocytes, hepatocytes, stem cells, etc.) in multicellular organisms is usually caused by aging. Spontaneous disruptions of cellular molecular processes are among the factors that contribute to the aging process (Sect. 11.2). They lead to the irreversible wear of cellular structures and an imbalance in the functional systems of metabolism. A cell maintains its existence only due to genetically determined mechanisms for counteracting chaos and maintaining integrity, primarily due to anabolic self-repair processes, such as the resynthesis of worn-out enzymes, structural proteins, lipids, and carbohydrates, as well as the recovery of worn-out macromolecular complexes and organelles. However, at a certain stage in a cell’s life, these programs and mechanisms are simply turned off or altered. Eventually, the rate of restoration of integrity simply cannot keep pace with the rate of wear. When cells approach the maximum life expectancy, the gradual aggravation of the effects of aging of their structures and functions always leads to natural death. Thus, the decisive role of the genome in aging and cell death is reduced simply to turning off the restoring programs, after which the cells gradually die. Accordingly, the duration of aging and the duration of the life of different types of cells is determined, apparently, by the varying times at which self-repair programs are shut down. In vertebrates, not only do the somatic cells age, but so also do the stem cells, which are the main instrument for self-repair of the multicellular body. These cells lose their ability to divide and differentiate asymmetrically, which leads to a cessation of renewal capabilities and rapid deterioration of the organs they compose. Cell proliferation is absent in the adult bodies of some primitive animals (certain nematodes, Drosophila, etc.), and this, apparently, is also associated with the shutdown of the corresponding genetic program after maturation. It leads to accelerated wear of the body and a short lifespan of up to 20–25 days. A special genome program, known as the Hayflick limit, is also used to restrict the number of cell divisions to about 50, after which the cell stops dividing and dies. The inability to divide is associated with a reduction in the size of telomeres, which are the sections of DNA at the ends of chromosomes. This also happens due to the shutdown of the genetic program for the formation of a special enzyme, telomerase, which lengthens the chromosomes. As a result, the production of telomerase stops, the end sections of the chromosomes are not restored, and the cell stops dividing, ages, and dies. Thus, one of the main causes of death is aging, which slowly but inevitably kills the cells that managed to escape other causes of death. (B) Genetically determined causes of death as a result of activation of special “killing” genetic programs. “Quick killing”

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The pathway of terminal differentiation of certain cells in animals can be presented as an example of a special killing genetic program. In particular, in accordance with certain programs of the genome, there is a gradual differentiation and transformation of skin keratinocyte cells into dead cells that form the stratum corneum of the epidermis. This occurs via the process of rapid terminal differentiation. The organelles are eliminated from these cells and they are filled with the insoluble protein keratin. As a result, the cells die within a few days, without showing any signs of aging. The process of binary division of somatic cells is a way to simultaneously remove worn-out cells and generate new ones. This is carried out using the genetic program of genome replication and its translocation into daughter cells. Two daughter cells are formed, and the mother cell “disappears”. This process can hardly be called death, it is more correct to consider that the mother cell perishes in the process of division, breaking into two independent parts. Since cell division is a strictly genetically controlled process, it can also be considered as a genomic tool to get rid of worn-out cells. Apoptosis is another good example of a killing tool defined by the genome. This is a genetically programmed, selective, targeted self-destruction of cells in multicellular organisms (Fig. 11.5). This mechanism destroys defective, mutant, and infected cells. Moreover, during embryonic development, this genetic mechanism is used to destroy large groups and layers of cells that have fulfilled their auxiliary role. The aforementioned genomic mechanisms of violent death are applied for the differentiation of organisms and the controlled selective removal of worn-out cells, but also to free up space for the appearance of new cells. Thus, programmed rapid death is characteristic of many cells. In this way, many cells die without going through an aging process and much earlier than the possible maximum duration of their life. (C) Biological causes of premature death, not genetically determined Many cells can die not only from internal cytogenetic causes, but also for external reasons. Indeed, cells can be attacked by bacteria or viruses and die from infections. For instance, bacteria of the genera Rickettsia, Shigella, or Chlamydia multiply in some cells of mammals and birds, causing increased wear and premature death. A huge number of viruses are also known to infect a wide range of animal cells. There are about 2000 known types of influenza viruses alone. They multiply in infected cells and destroy them when they exit. Cells can also die prematurely due to phagocytosis. Sudden massive cell death can be associated with the death of a multicellular organism. Cells can die prematurely from a violation of trophism and the lack of the ability to consume water. Cells can also degenerate, be “ill”, and die because of metabolic disorders or the accumulation of toxins. So, there are indeed many different premature causes of death of a biological nature, not related to any genetic cause.

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(D) Physicochemical causes of death. Premature and accidental deaths Many free-living unicellular organisms die prematurely and accidentally due to geophysical disasters (volcanic eruptions, drought, fire, etc.) or changes in habitat conditions (changes in temperature, water cuts, irradiation, availability of food, etc.). Besides, multicellular organisms also die, taking with them the lives of their whole cell population. Within the composition of a multicellular organism, cells are also susceptible to unprogrammed premature or accidental death for physicochemical reasons, such as poisoning, lack of oxygen, frostbite, burns, radiation, mechanical injuries, and so on. Two routes to demolition and utilization of cells. Cells that have died in a multicellular organism are inevitably demolished. This is achieved via two main mechanisms—necrosis and apoptosis (Fig. 11.5). Necrosis is the gradual destruction of intracellular contents after various lethal injuries by autolysis (self-digestion due to endogenous enzymes). Necrosis is characterized by swelling, denaturation, and coagulation of cytoplasmic proteins, destruction of cell membranes and organelles, and finally, destruction of the entire cell. Usually, necrosis is caused by various external factors (mechanical, chemical, physical, or biological) that disrupt the structure and function of membranes or alter the synthetic and energetic apparatus. The result is a violation of the internal homeostasis of cells, expressed as a change in the ionic composition, substrates, ATP, enzyme activity, etc. Compartmentalization is impaired, the cell loses its metabolic and functional activity, while lysosomal enzymes, which exit from the damaged lysosomes, become activated and gradually lyse the cell down to small fragments or monomers of macromolecules that are absorbed by macrophages. Apoptosis is a genetically programmed cell death of multicellular organisms; it is a purposeful self-destruction of cells. The main function of apoptosis is the destruction of defective (worn out, damaged, mutant, infected) cells. Apoptosis is also involved in the processes of differentiation and morphogenesis of multicellular organisms. Apoptosis is found in a number of prokaryotes and in all eukaryotes, from unicellular protozoa to higher animals. Apoptosis can occur both after cell damage and without a primary disruption of the structure or cellular metabolism. The action of various stimuli on special membrane receptors results in activation of special death complexes called apoptosomes, which contain caspases, destructive hydrolytic enzymes. The main function of these enzymes is direct destruction of cell structures. The proteins of the nuclear lamina undergo hydrolysis, the cytoskeleton is demolished, proteins that regulate cell adhesion are cleaved, etc. Furthermore, the nucleus and cytoplasm are fragmented, and the plasma membrane “swells”. Signals for self-destruction can be hormones or various signaling proteins. Another, internal, mitochondrial signaling pathway of apoptosis is realized as a result of the release of apoptogenic proteins from the intermembrane space of damaged mitochondria into the cytoplasm of a cell. One of the consequences of apoptosis is DNA fragmentation under the action of nucleases. The cells disintegrate into large fragments called apoptotic bodies, which are devoured by phagocytes or autolyzed by enzymes, without inflammation.

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The process of apoptosis in mammals is rather intense. For example, about 50 billion cells die every day in a human body as a result of apoptosis, and the total mass of cells that undergo programmed destruction during the year is equivalent to the body weight. At the same time, the complete replacement of the lost cells is ensured by the division of stem and committed cells.

11.3.2 Death of Multicellular Organisms Multicellular organisms are rather different from cells in terms of organization and functionality, as described in detail in Chap. 5. Therefore, the mechanisms of their aging and death are significantly different as well, although the principles and causes of death remain the same (Table 11.3). (A) Genetically determined causes of death as a result of violations or interruption of genetic self-repair programs. Death from aging or “slow killing” The fundamental difference between multicellular organisms, such as animals, and unicellular creatures is their significantly higher level of organization. They consist of numerous tissues, organs, and cells together with their structural and functional systems, with stable interdependent connections and regulatory systems established between them. The subtle interaction of these systems maintains thousands of homeostatic indicators for the whole organism under the guidance of the neuro-endocrine system. The slightest disruption in the work of any link in the chain of relationships can lead to wear, aging, or even fatal consequences. Therefore, in addition to the characteristic causes of cell death (Sects. 11.2 and 11.3.1), extra causes are inherent in multicellular organisms. Natural death or the death of complex organisms associated with their approach to the maximum lifespan occurs due to progressive aging and chronic diseases of the body as a whole. They are caused first and foremost by a violation of self-repair systems and the maintenance of homeostasis. It seems that genetic programs to support the integrity and homeostasis of animals are gradually turned off upon completion of development and when puberty is reached (Fig. 11.2). Nature then leaves the body to its own devices, after which the levels of orderliness and functionality begin to decrease gradually under the influence of unfavorable factors of both internal and external origin (Sect. 11.2). This is what causes the natural aging of cells, tissues, and organs. In old age, demolition processes prevail over anabolic ones, which leads to an imbalance in almost all functional systems. From a certain point, the renewal processes slow down noticeably, damage accumulates in the body, and this leads eventually to a natural ending, i.e., the body dies. Hence, the cause of natural death in a multicellular organism is a fatal accumulation of disorders, both in cells and in the systems of support, regulation, and control of groups of cells, organs, body parts, and functional systems. In particular, with age, all structural and functional systems of animals wear out, including the central nervous system, but also the endocrine, cardiovascular, musculoskeletal, digestive, and other systems. A dilapidated organism is unable to restore itself to a healthy

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reproductive body due to substantial blocking of genetic self-repair programs. Only after the genome is “reset” in the process of reproduction and resumption of development programs is it possible to recreate new living bodies with a certain margin of safety. Thus, the decisive role of the genome in aging and in natural death from aging in animal organisms is simply reduced to turning off regenerating genetic programs, and the life expectancy of representatives of different biological species is determined by a different order and different timing in the turning off of these programs. (B) Genetically determined causes of death as a result of activation of special genetic “killing” programs. “Quick killing” Multicellular living bodies are also susceptible to premature death determined by the genome. For example, as a result of genetically determined malignant cell degeneration. This is accompanied by exclusion of such cells from the general wellcoordinated system of the body, their distribution and atypical localization, obstacles to the performance of physiological functions and regulations, as well as excessive consumption of substances and energy. As a result, the integrity and homeostasis of an organism are violated, leading to rapid exhaustion and death. Such events can occur at any age and usually end tragically for the individual. For animals developing with metamorphosis, despite having the same genome, it is typical to have several different bodies at different stages of ontogenesis. For example, butterflies with a complete transformation cycle can exist in the form of caterpillars, pupae, and adult images. During every transition from one stage of development to another, the death of the previous organism occurs and the emergence of the next. These deaths are caused by various programs of a single genome, which successfully passes from a dying body to another living body. Semelparous animals (mayflies, pink salmon, squid, etc.) die suddenly, usually immediately after reproduction. This phenomenon is considered a variant of phenoptosis—“deliberate” destruction by the genome of its outer body, which becomes unnecessary after reproduction. Death is caused by the inclusion of special programs of the genome, which abruptly limit the vital functions of individuals. For example, the bodies of pink salmon undergo hormonal changes and depletion just before spawning. Their jaws and teeth are transformed, they practically lose the ability to feed, as a result of which there is a rapid depletion and degeneration of internal organs. They have enough strength only for spawning, after which they immediately die. After death, a lifeless body usually remains for some time. Then a gradual demolition of cells and various parts of the body takes place. In the end, not a trace remains of the former bearer of life. But the life of the genome goes on! (C) Biological causes of death. Premature, not genetically determined An enormous variety of microorganisms and viruses can enter multicellular organisms and cause many infectious diseases that end in death. Pathogenic agents cause poisoning and death of organisms by secreted exotoxins or endotoxins. They can cause epidemics and pandemics, leading to a massive death of living bodies. For

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example, the 1918 influenza pandemic (Spanish flu) killed 20–80 million people, which was approximately 2–3% of the world’s population. Damage, injury and disease of organs and their systems, caused by various reasons, are also the basis for the premature death of organisms. For example, diseases of the cardiovascular system in humans (heart attacks, strokes) are one of the main causes of death, even at a relatively young age. Under natural conditions, hunger is a significant factor in the premature death of organisms. To avoid hunger, animals make thousands of kilometers across the planet and mortally fight for territory and food. Probably, the almost complete death of plants and the disappearance of a food source for herbivores after the fall of a meteorite in Mexico 65 million years ago, caused the rapid extinction of not only dinosaurs, but hundreds of other biological populations and species. Majority of living organisms contain approximately 65–75% liquid water. Water provides almost all processes and functions of organisms. It is continuously used in the metabolism and excretion of toxic metabolic products, and also constantly evaporates (in terrestrial organisms). A decrease in the amount of water, for example, in the human body by 20–25% is fatal, and physiological disturbances occur already with a loss of 1–2% of the total amount of water in the body. Organisms in arid regions of the Earth have special adaptations to prevent water loss. However, in the absence of a water source for a long time, they die prematurely. Predation is a type of relationship between animals in which individuals of one species are killed and eaten by individuals of another species. If a number of predators is too large, their prey can die prematurely en masse and even disappear from the face of the Earth. Thus, it is obvious that a huge number of organisms decease long before aging and reaching the maximum lifespan. (D) Physicochemical causes of death. Premature and accidental Many organisms die as a result of geophysical and environmental disasters (for example, forest fires, floods, the fall of large meteorites, volcanic eruptions, and anthropogenic factors). Therefore, a significant number of organisms often die in extreme situations from various thermal, mechanical, and baric injuries and even shock waves. In the summer, in heat and drought, they are threatened with overheating and dehydration, and in winter, death can occur as a result of frostbite or freezing. They also face a mortal danger of poisoning by various chemicals (fertilizers, pesticides, etc.), which can be introduced by humans into the soil of fields and forests, as well as in water basins. Many organisms are highly sensitive to various kinds of radiation and a range of other physicochemical impacts, which can lead to their death before the natural allotted time. Thus, aging is not always obligatory for living bodies, but their death is inevitable for many other reasons. That is, many organisms actually die prematurely, without knowing the delights of aging. Only those individual organisms that live all their life in favorable conditions can reach an extremely old age. That is, death from aging is only part of the global process of the death of living bodies. A large fraction of organisms die much earlier, meekly submitting to fate. Perhaps, only humans attach

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great importance to their own life and death, seeking to live indefinitely, without growing old, and always in good health. Interestingly, even hours after the death of a multicellular organism, for example, a mammal that has died due to a destructive brain injury, when the basic connections of the multicellular system are irreversibly disrupted and the main organs no longer function, some of the cells continue to remain alive. Such individual cells can still function for a while, depending on the internal supply of nutrients and energy. This phenomenon is what allows post-mortem donation and transplantation. For example, after the accidental death of a person, their organs (heart, kidneys, skin, etc.), even procured for transplantation a few hours later, can retain viability for a number of hours and even days. Thus, the death of a multicellular organism as an enormous complex system of cells, tissues, and organs is a gradual and asynchronous process. It consists in the gradual disappearance of emergent properties that support life at different levels of the body’s organization. In particular, violation of the highly complex system of nervous regulation, termination of the action of the cardiovascular system, violation of the systems of external and tissue respiration, an imbalance in the finely balanced neuroendocrine system, violations of the branched system of tissue nutrition, termination of protein synthesis, and so on. Only then will all organs and tissues cease to function, stopping the metabolism of cells, and this happens at different times and to varying degrees in different parts of the body. It turns out that the death of a complex organism has two stages: (1) termination of its existence as an integral individual; (2) death of all cells that make it up and contain its genome. As long as at least one cellular genome remains alive, there is still some potential for the revival of this organism. For example, germ cells can be extracted from tragically deceased men or women, artificial insemination can be carried out, and their genomes can be “reborn” in a new phenotypic framework. Cloning also confirms the central role of the genome in the processes of death and rebirth. Even despite the inevitability of the natural death of any living body, it is a dramatic fact that the genome also voluntarily limits the lifespan of each individual. Moreover, although an organism can fight for some time against the increase in entropy, it cannot by any means escape its genetic death sentence. The immortal genome does not provide any opportunity for its phenotypic framework to exist longer than it wants.

11.4 The Ambiguity of Death As explained in the previous sections, the lifetime of all organisms is limited. The lifespan is limited for many reasons. Only a few organisms survive to the maximum possible term, and none can go beyond the limiting time line drawn by the individual genome. The life of any organism inevitably has a tragic end.

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As noted above, death is a natural event after a certain period of time. The maximum lifespan, as a phenotypic trait of a given biological species, is inherited. Therefore, trillions of individuums of billions of generations of various species have lived, live, and will continue to live only for clearly defined times (Table 11.1). Many examples testify to the genetic conditionality of the time of death of living bodies. In particular, mayflies live only one day. During this period of time they mate, the females lay eggs, and all individuums die. Depending on the patterns of the genomic cycles of ontogenesis, the adults of many insects live for only a few tens of days, while their larvae can live for years. The males of some squid die, courtesy of the genome, immediately after the females are inseminated, as they have played out their role. That is, death in the listed cases has a positive value and is caused not by aging, but by sudden genetically determined, hormonally caused self-destruction (phenoptosis). Obviously, the duration of an individuum’s life is rather irrelevant for the system of genomes of a species. It is their successful reproduction that matters most for the genome. There are several more examples of the positive value of death. In particular, birth and death determine the global process of the exchange of living bodies, the change of generations (Sect. 9.8), and evolution (Sect. 8.5.4), which are the necessary conditions for maintaining the immortality of the phenomenon of life. The death of old organisms ensures the change of generations, leaving a place for new, young, and healthy individuals. They have new combinations of traits that ensure the survival, adaptation, distribution, and evolution of all life on the planet. Death and reproduction maintain optimal numbers of individuals. Reproduction in the absence of death would lead to overpopulation, which would mean a restriction of territory and food for most organisms. Death frees the planetary system of life from decrepit ballast, incapable of reproducing genomes. That is, the existence, survival, and progress of populations and species are controlled by the processes of death and reproduction of individuals, which are in turn controlled by the programs of the genome. The positive value of death is also manifested in numerous functional uses, where the remains of dead cells or their derivatives play an important natural role in the life of some organisms. For example, in plants, mature sclerenchyma cells lose their cytoplasmic content, form thick walls, and die. But their preserved walls provide mechanical strength and support to the plants. The wood of trees contains vessels that provide the flow of water and solutes. The walls of these vessels are also formed by dead cells. The dead cells form the hair, claws, horns, hooves, and feathers of animals, which are of great importance in their life. The outer layer of animal skin also consists of several layers of dead cells, which protect the body from water loss and prevent the penetration of microorganisms. During the development of organisms, many cells are genetically determined to die at a certain time and place. For example, the cells in the tail and external gills of a tadpole die at a certain stage of development, allowing it to become a frog. During embryonic development in mammals, body cavities, vessels, and organs are also formed through genetically programmed cell death. Thus, along with the natural death of living bodies, additional genetic mechanisms have arisen in the process of evolution whose action leads to the inevitable death of

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individuals, in a way which is generally favorable for populations and species. The interests of an individuum are sacrificed for the prosperity of a community or the population of a particular genome. It should be emphasized that the genomes of individuals do not disappear with the death of organisms. The mass death of individuals is opposed by the preliminary mass reproduction of their genomes. Their reproduction is based on DNA replication, duplication of the genome as a whole, and its subsequent transit to daughter organisms. That is, it is the genome that is the main actor in this process. Only the genome possesses the property of permanence, which it passes on to subsequent generations, ensuring the immortality of the phenomenon of life. This means that reproduction is in fact the process of replication by genomes of themselves, and their transit into daughter organisms using the properties of the living bodies in which they live. Moreover, with the emergence of a new daughter organism, life as a phenomenon does not appear anew out of nowhere; only a mortal body appears, in the form of a new phenotypic framework for the immortal genome as it travels through time. The mortal body is doomed to perish, but for the genome this does not matter. Death appears as an inevitable stage of its renewal. Therefore, death is far from unambiguous. It is tragic for the individuum (which disappears), indifferent to its genome (which safely passes into other bodies), but has a positive value for species, communities, and for the entire planetary system of life (which death clears of decrepit ballast).

11.5 Phenotypic Death and Genotypic Immortality Apparently, the rudiments of life first appeared as manifestations of genotypic life (see Chaps. 8 and 18; Fig. 8.2), without pronounced phenotypic expression, in the form of replicating nucleic acids and polypeptides in some amorphous colloids. Further, under certain conditions, various combinations of functioning nucleic acids and proteins began to improve their surroundings for adaptation and survival with a “phenotypic framework” that varied depending on their habitat. Thus, complex living systems were gradually formed and phenotypic life (bodily life) appeared in the form of primitive prokaryotes. They already possessed autonomous bodies that mediated between the genome and the external environment. In this way, life appeared as the existence of mortal living bodies. We observe only an obvious change of generations of the representatives of phenotypic life, which are the intermediaries between the genome and the changing external world. We do not perceive the genotypic part of life, since it exists in the processes of replication, transcription, translation, and many other molecular mechanisms that remain hidden from our eyes, but which determine the existence of the living bodies we observe. Thus, one can imagine the process of the lives of bodies as if in two dimensions (Sect. 18.5). There is the continuous genotypic life hidden from our eyes, which is a set of processes ensuring the existence and functioning of all elements of a genome and the realization of its information potential; and there is the intermittent phenotypic

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life we see, which is a set of processes ensuring the existence and functioning of living bodies. Then it is quite obvious that irrevocable death concerns only the phenotypic framework of the genome, only the phenotypic aspects of life, whereas genotypic life does not stop and, after reproduction, continues in another body. The lives of individuals end in death, and are never renewed again. That is, selfreproduction of themselves is impossible. But their genomes come to life in other bodies. Consequently, organisms should be perceived logically speaking as a means of survival and reproduction of genomes. After all, it is the genomes that systematically reproduce themselves, and then participate in the processes of reproduction, growth, development, and maintenance of integrity. After all, it is for them that the cyclical nature of existence or, one might say, the “life cycle”, is characteristic. Indeed, even with the death of the carrier organism, the existence of the genome does not end, provided it has left offspring (see Chap. 9). Hence, after the death of an individuum, life as a phenomenon does not cease. The substrate of an individual’s life in the form of an aggregate of its DNA, passed on to descendants in the process of reproduction, continues to live in their bodies. In the next life cycle, the genome of the new individual will again be passed on to the next generation, maintaining the genetic continuity of life. Consequently, only a certain body, a discrete carrier of phenotypic life, perishes and is destroyed, while the existence of a discrete unit of genotypic life continues in other bodies. Accordingly, it is the genomes of certain species of organisms (species of genomes) that actually live for many thousands and millions of years (and generations). Thus, life as a phenomenon does not age and never dies. It travels from one mortal body to another in the form of immortal genomes, continuing to exist for billions of years, in successive living systems. Phenotypic life in the form of living bodies is not eternal. It is subject to aging and obligatory death. It is only a temporary home for the genome, where it is cloned, and with the help of which it multiplies and spreads. In these bodies, periodic recombination of hereditary material also occurs. The genome, without fundamentally changing, acquires new alleles and their combinations. That is, living bodies are just a convenient transitory form of a genuine carrier of life, and the duration of the existence of organisms (from one day to thousands of years) is not of fundamental importance for the eternal process of biological progression. It is perhaps saddening to realize that we are only a representative of a short phenotypic life, the “disposable body” of an infinitely ruthless genome, our own genome. On the other hand, we can be proud of ourselves (our own bodies) if our duty to Nature has been fulfilled by reproducing and passing on our genome to our descendants. This fact fully justifies our temporary existence and fills individual life with its grand meaning. Mediating bodies have complete forms and properties, which prevent them from always being able to supply an adequate response and adaptation to changing environmental conditions. Therefore, they are doomed to perish. In order not to disappear, genomes, as the masters of bodies, must change them in accordance with the conditions in which they may be required to live. To do this, they only need to slightly change their genetic program. For this purpose, they have special mechanisms for

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making rearrangements in the process of reproduction. Informational microchanges are multiplied in the process of further expression, and as a result, bodies are built with new features and new versions of their combinations. Natural selection does its job in destroying phenotypes that do not live up to the current requirements. As a result of this struggle, the winner is the permanent genome, as it settles down in its renewed body. The phenome is dead! Long live the eternal genome and its new phenome! Thus, despite the natural death of individuals, life as a phenomenon is continuous, and the existence of species continues for many millions of years due to the phenomenon of individual reproduction, which is the transfer of permanent genomes to subsequent generations of phenomes that are doomed to die. Consequently, after the death of individuals, only the phenotypic component ceases to exist, while genotypic life continues in the offspring.

11.6 The Illusion of Death and the Illusion of Life The illusion of death. Why are all living bodies mortal? Why did Nature forcibly limit the lifespan of individuals? Why does it destroy all living bodies so inevitably and so remorselessly? The fact is that the processes we witness leading to the deaths of individuals are in fact only an illusion of the collapse of life or an illusion of death. Indeed, in fact, the existence of the genome, as the true object and carrier of life, does not end in any way. In the overwhelming majority of cases, it first replicates and then passes by mitosis or meiosis into daughter bodies, which become its new phenotypic framework. Thus, the genome is never destroyed. That is, the death of bodies is only an illusion of the termination of life, since in fact the existence of genomes goes on uninterrupted. And the bodies we see are just a consumable for genomes. This is a “disposable body” that the genome uses for its own survival and reproduction. The illusion of life. Visually, we perceive only the outer shell of life in the form of the phenotypic framework of the genome. It is this shell that moves, feeds, breathes, multiplies, and defecates as a single intricate body. So, it is alive! So, it lives! But this is a deception and an illusion! Actually, it is the genome that deftly manipulates its outer shell for its own survival and reproduction. Its shell nourishes it, protects it, moves it, and promotes reproduction in every possible way. In fact, the genome continues to live, changing only its place of residence.

11.7 The Value and the Price of Individual Life and Death The conscious attitudes of we human beings to our lives lead to a subjective perception that life is the main value of nature. This greatly complicates our understanding of its naturalness and simplicity. When we look at most other organisms, it is quite obvious that neither worms, nor insects, nor birds (not to mention plants and fungi)

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attach any special importance to either life or death. These biological robots live according to strict genetic programs. They have a powerful hereditary instinct for selfpreservation, avoid danger, survive, and reproduce. But most living beings (perhaps, except humans) are totally submissive and indifferent to the value of both life and death. For example, many social insects (bees, ants) even calmly sacrifice themselves for the good of their family. They blindly follow the orders of their genome, as if realizing that the death of some millions of DNA clones out of many trillions has no meaning for the prosperous existence of their species. Thus, the individual life of organisms has no particular value for stable populations and species. The survival of taxa and their long-term existence is ensured by the reproduction of individuals, the essence of which is the continuous transit of genomes from mature bodies to young ones (see Sect. 9.7). That is, genomes pass unharmed, both through life and through death. This is what supports the unique, almost immortal, planetary phenomenon of life. However, the price of such natural and at first glance unconstrained lives of organisms is extremely high. In particular, almost the whole of the precious lifetime of an animal is spent looking for, consuming, and assimilating food, avoiding or protecting itself from enemies, fighting for territory, adapting to and counteracting unfavorable environmental factors, reproducing, and protecting offspring. All the consumed matter and the energy produced by cells is used for self-repair and maintaining the life of their incorporating organism. Consequently, almost all the vital activity of living bodies is aimed precisely at the survival and continuation of the genus. That is, the price of life for an individual is life itself, with which the genome pays Nature for its own immortality.

11.8 Summary Aging is a programmed natural process of wear of ordered, highly organized biological structures and systems. That is, all organisms gradually age as a result of the accumulation of damage. The rate of this accumulation (the rate of aging of organisms) is determined first and foremost by genetically appointed expenses directed against the increase in entropy and toward the maintenance of integrity and homeostasis. Such programs of the genome do not last forever, but only for a certain time, sufficient for the genome to reproduce itself. As a result of their “responsible” shutdown, living bodies are left to fend for themselves. This is accompanied by a sharp increase in the rate of spontaneous aging and the rate of approach to their final moments. In different organisms, programs to combat entropy are switched off by the genome in different ways and at different times, and this is what determines the difference in the rate of wear and longevity. That is, the differences in aging processes in diverse organisms are the result of different levels of efficiency in this struggle. Thus, aging and death are mainly due to thermodynamic and genetic causes. Everyone grows old in different ways, but everyone dies in due time and in the same way—from an irreversible termination of the struggle against entropy.

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Individual life is a dynamic process which concerns the limited existence of discrete units of life from the moment of their appearance to death. Individual life is based on the constant flow of a set of physicochemical and biological processes aimed at maintaining existence. It is passed down from mortal ancestors to similarly mortal descendants, from generation to generation, through the reproduction of their immortal genome. An individual death is the moment of irreversible cessation of the basic processes and functions that support life. From a systemic point of view, aging is a gradual disruption of the ordered organization of living systems, and death is an irreversible destruction of the organization of systems, leading to the loss of their emergent biological properties. Death is a hereditary phenomenon in the life of every organism and is a natural and inevitable event after a certain period of time. Death is tragic for the individual, indifferent to his genome, but has a positive meaning for species, communities, and the planetary system of life. Genesis and death determine the global exchange process of living bodies, which is a necessary condition for maintaining the immortal planetary phenomenon of life. The lifespan and inevitable death of individuals (phenotypic frameworks of genomes) is due to and unambiguously limited by thermodynamic, stochastic, and directly genetic causes. Fighting them is absolutely futile. But the lifespan of the genomes of individuals is virtually unlimited. As a result of replication and division, they continue to live in other phenotypic frameworks without any significant changes.

Chapter 12

Survival Pathways for Living Bodies and Their Genomes

It is obvious that living bodies are very vulnerable. They consist of naked, delicate, pliable cells that do not have significant levels of protection against environmental factors. In particular, low and high temperatures, lack of food and water, pressure drops, radiation, mechanical impacts, and the action of toxins can all be harmful and even lethal to them. Yet life on Earth emerged under just such geophysical conditions. Moreover, the natural situation on Earth is constantly changing, and from time to time it changes in a catastrophic way, killing everything in sight. Cells and living bodies wear out as a result of the action of thermal motion, constant work, toxins, superoxide radicals, and other continuously unfavorable factors (see Chap. 11). However, despite the genetic and thermodynamic gloom and doom, living bodies have existed successfully on Earth for several billion years. Consequently, there must be special methods and mechanisms that allow organisms and the planetary system of life to withstand these destructive pressures and other unfavorable devices of Nature.

12.1 Maintaining Integrity and Homeostasis: Self-repair All material objects are constantly exposed to manifold internal and external environmental factors: the thermal motion of molecules, various types of radiation, temperature fluctuations, mechanical influences, etc. The result is damage and wear to various physical bodies and systems, including living organisms. Organisms would quickly die if there were no special mechanisms of constant self-repair to maintain their integrity and homeostasis. In Chap. 5, it was noted that homeostasis is one of the most important characteristics of living bodies and the main condition for their stable long-term existence. This is the constancy of the parameters of the internal environment, structure, and functions, which can be maintained for a relatively long time. The term “self-repair” emphasizes the presence in living bodies of internal genetic programs, biochemical and physiological mechanisms aimed at maintaining their structural and functional monolithicity. These mechanisms work at © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_12

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all organizational levels of the organisms, renewing worn out structures and restoring functions. Constant renewal of macromolecules and cell organelles. The lifetimes of the enormous variety of protein molecules extend over an extremely wide range, from seconds to decades. Worn out proteins are broken down by proteases to yield amino acids, and new functionally active macromolecules are formed anew from these. This process is extremely intense. Similar processes occur with other macromolecules and their complexes, and also with organelles. Continuous DNA renewal is provided by molecular repair processes, which instantly restore damaged segments using special enzymes. In addition, the preservation of an unaltered structure is facilitated by periodic replication processes that occur with DNA molecules just before every division of genetic material, and before division of the cell itself. In the process of replication, enzymes control the integrity of nucleic acid molecules and, if necessary, “repair” them. The renewal of the cellular and genomic composition of tissues in multicellular organisms is carried out by replacing damaged or worn out cells with new ones. On average, for example, mammalian cells live and function from several days to several months. Worn out, damaged cells are eventually destroyed by the enzymes of their own lysosomes; they are fragmented, and the fragments are absorbed by phagocytes. Dead cells are replaced by new functionally active cells that appear after asymmetric division of stem cells and differentiation of one of them (Fig. 12.1). A range of stem cells is present in nearly all tissues and organs, providing continuous renewal and restoration of the whole organism. However, as the body ages, its Fig. 12.1 Stem cells are the custodians and disseminators of the individual genome. Masters of a powerful potential for development and maintenance of integrity, stem cells have the unique ability to divide asymmetrically many times. Their division gives rise to similar daughter stem cells with an identical genome as well as committed cells with a genome dedicated to a certain path of differentiation

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stem cells also age. Gradually, they reach the Hayflick limit and lose their ability to divide. Their number then decreases and the recovery processes deteriorate. Some cells exist in the body throughout life (neurons, lens cells, heart muscle, etc.). Such cells were formed in the embryonic period or in the early stages of postembryonic development; they never divide and, if they die, can never be replaced. The mechanism for the long-term maintenance of tissues with permanent cells is a constant genetically programmed renewal of enzymes, structural proteins, biological membranes, cell organelles, and parts of cells. For example, neurons can serve for tens of years only thanks to the constant renewal of their cellular components. Many vertebrate cells are not permanent—they are replaced periodically by new ones. An example is liver cells. If a substantial fraction of the liver cells are destroyed due to trauma or intoxication, the rate of division of the remaining hepatocytes increases significantly to replenish the loss. Progenitor hepatoblasts provide the main contribution to this division. In such cells, signaling molecules trigger genetic mechanisms that activate division and differentiation. Every tissue or organ is made up of numerous types of cells. For example, the skin contains fibroblasts, its blood capillaries are composed of endothelial cells, nerve endings are an extension of nerve cells, etc. The organization of this mixture of different cells, which are continuously dying off and being replaced by new ones, is maintained according to the cellular memory of each cell line. That is, exactly the same type of cell replaces the dead one. Such a transfer of specialization to daughter cells provides a way of maintaining the structure, functions, and homeostasis of organs. The integrity of multicellular organisms is also maintained through reparative regeneration, i.e., the restoration of damaged or rejected organs or body parts. The causes of damage can be mechanical trauma, burns, frostbite, radiation, the action of poisonous substances, etc. For example, a planarian flatworm can be mechanically divided into several parts and each part is able to restore itself to a complete organism. Significant parts of the body can be removed with subsequent regeneration in annelids, sea stars, and some mollusks. Some arthropods, amphibians, and even reptiles can restore limbs. In particular, salamanders can regenerate limbs, tail, and even eyes. In mammals, the healing of skin, bone fractures, and damage to internal organs is also an example of reparative regeneration. It is based on the effect of re-arrangements of gene expression, the inclusion of programs for the selective differentiation of dividing cells, and the restoration of a certain part of the body. The maintenance of integrity and homeostasis is very costly. It would be impossible without the expenditure of matter and energy. Furthermore, all assimilated matter and up to 90% of the energy produced by the body are spent on maintaining homeostasis. An equally important condition for maintaining standards of integrity is the use of genetic information, which controls the formation of the necessary components of complex biological systems. The main molecular process is biological synthesis, which ensures all major aspects of the maintenance of integrity. That is, living bodies involve colossal internal dynamics in the exchange of their constituent components against a background of constancy of composition,

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volume, and shape. Alternatively, one might say that the constancy of the composition, volume, and shape of living bodies is maintained thanks to the colossal internal dynamics involved in the exchange of their constituent components. Living beings make good use of spontaneous destruction in the overall process of their own recovery. After all, without destroying the old, it would be impossible to build anything new. The dissipation of living bodies based on the second law of thermodynamics is highly beneficial for the phenomenon of life, since there is no need to spend additional energy on the destruction of the old. That is, moribund organisms die naturally, without the need to use their own forces and energy. The expenditure of biological energy is necessary only to counteract entropy, reproduce, develop, and maintain the integrity of new organisms. Consequently, life uses the laws of thermodynamics for its own selfish goals of survival and permanent existence. Thus, the main condition for the long life of organisms, their integrity, maintenance of homeostasis, and high degree of order is constant, controlled self-repair. Due to this, living bodies maintain homeostasis at all levels of their organization. At the same time, all the processes involved in maintaining the integrity of organisms and cells are subordinated to the key task of preserving the genome’s own homeostasis via the continuous renewal of its phenotypic framework.

12.2 Reproduction of Genomes The opposition of organisms to entropy cannot last forever. The increase in entropy inevitably leads to the destruction of organized systems. In order to be stable and not disappear, living bodies must constantly fight against spontaneous destruction through self-repair. But this is possible only for a certain time, since the rate and intensity of wear eventually prevails over the possibilities of recovery. The death of individual cells and organisms is inescapable. Yet, life on Earth in the form of a planetary system continues! This happens because living bodies, before disappearing, manage to leave behind offspring thanks to their ability to reproduce. That is, the mechanism of reproduction of living bodies is used for the reliable and long-term existence of biological species, their genomes, and the phenomenon of life itself. All species multiply and create copies of their own kind on the basis of the replication properties of DNA molecules. In fact, the mechanism of genome reproduction ensures the survival and continuous transfer of genomes from one mortal body to another over millions of years (see Chap. 9). Despite the fact that cells and other living bodies are capable of regeneration and adaptation, they still exhaust their resources of resistance. They do not have enough time to recover, and this leads to an accumulation of damage and mutations, genetic programs fail, and metabolism is disrupted. As a result, they will certainly lose their strength and ability to reproduce. This in turn deprives taxa of the ability to evolve, which poses a threat to the existence of the planetary system of life. Therefore, it was not beneficial for Nature to exert any extra effort to endlessly maintain decaying

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living bodies. It was more expedient to genetically limit the duration of an individual life. As a result, programmed death has become an inevitable event for all individuals without exception. At the same time, to ensure the permanent existence of life as a phenomenon, living nature uses the mechanism of “reincarnation” of genomes (Chaps. 9 and 17). This reliably ensures the immortality of genomes and the successful survival of species and their evolution. Importantly, during cell reproduction, “old” mother cells die and new “young” ones appear. In this way, they are almost completely updated. The genome renews itself and completely renews its phenotypic framework. In particular, virtually complete elimination of worn out cell organelles and proteins occurs during the preparation for division in the G2 phase of the cell cycle, and a homogeneous mixoplasm is formed instead of a heterogeneous cytoplasm. Renewed organelles, proteins, and enzymes appear again in the cytoplasm of daughter cells only after cytokinesis. Moreover, there is not only a doubling of genetic information in the process of replication at the S stage of the cell cycle, but also a complete enzymatic revision of DNA molecules, the elimination of all possible mutations, and their complete renewal. Thus, the cell’s death-revival strategy enables almost complete periodic renewal of cells and their contents, as well as “resetting” the genetic programs of genomes, which allows them to survive and exist for billions of years. That is, the death of cells does not mean termination of the life of their genome, because it successfully moves into a new living body after mitosis or meiosis. Nature developed this strategic mechanism of reproduction and transmission of genomes to maintain the continuity of life of all types of cells and organisms. The permanence of the planetary system of life on Earth is also based on the constant reproduction of the short-lived constituent elements, which we call “the exchange of living bodies” (Sect. 9.8). These elements are cells or cell systems, in the case of multicellular organisms. The carriers of an individual life are each time recreated using the information programs of the genome, which travels continuously, practically unchanged, from one body to another. That is, each mortal generation of living bodies is merely one of the stages in the existence of numerous cycles of development of eternal genomes.

12.3 Adaptation and Evolution All organisms are well adjusted or adapted to their habitats. This was achieved in the process of a long co-evolution of the Earth and life. Living organisms gradually became adequate to the living conditions of temperature, aqueous environment, atmosphere, gravity, solar radiation, radioactive background, etc. All this is reflected in their structural and functional organization, including various specialized metabolic processes (for example, photosynthesis or oxygen breathing), functional capabilities (the ability to fly, swim, walk, etc.), special organs (respiration, nutrition, movement, reproduction), as well as body parts (the presence of limbs or the fact that the front part of the body carries analyzers).

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Such adaptability and vitality of living bodies arose via natural selection from an infinite number of variants of phenotypic traits supplied by mutations and recombinations, which became firmly entrenched in the genetic apparatus and are accurately transmitted to subsequent generations through the reproduction of genomes. This is a genotypic adaptation that has occurred through many sequential mutations or recombinations of genes under the influence of environmental factors. Such adaptations develop over a very long time. They lead to significant changes in the genotypes and phenotypes of organisms. The emergence of new alleles of genes and their new combinations brings about a change in the qualitative and quantitative composition of structural and functional proteins, as well as the appearance of new types of enzyme, which in the end ensures the manifestation of new traits or their variants. Among these myriad variants of organisms, only those possessing useful traits survive and reproduce, while natural selection destroys the rest. The adaptation process is a change in an organism over a period of time in a direction that increases its chances of survival under changing conditions. Since the environmental conditions on our planet change over time, adaptations can also vary, improve, or even disappear. Thus, many adaptations are relative, as they arise in response to a specific environmental challenge. In other ecological conditions, such adaptations do not perform an adaptive function, and with the disappearance of an environmental challenge, the acquired traits turn out to be useless. Adaptive changes can go in the direction of complication (for example, the appearance of a skeleton, the ability to fly) or simplification of the structural and functional organization (for example, the loss of the respiratory and circulatory system by some internal parasites). One and the same challenge in adaptation to the external environment can be solved through different approaches. For example, different animals have learned to avoid the adverse effects of low temperatures using different mechanisms. Some have acquired the ability for seasonal migration, others fall into a torpor in special underground shelters, others have developed special mechanisms of thermoregulation, still others thermal insulation, etc. All of these are examples of different variants of phenotypic adaptation caused by various genome mutations and then selected by natural selection. The environment in which living beings have entered is not only a material one, for it also contains a set of dynamic spatio-temporal phenomena. Among them there are constant impacts (gravitation, radiation), episodic events (precipitation, earthquakes), and periodically repeating phenomena (seasons, sunset and sunrise). As a result of adaptation and evolution, all organisms have in one way or another reflected all this in their organization. In particular, gravity has caused many organisms to have an upper and lower body. The frequency of precipitation in some arid parts of the planet has led to the appearance of organisms that periodically fall into torpor during drought and reactivate when precipitation returns. The changing seasons ensure the seasonality of reproduction and development in many plants and animals. These phenotypic manifestations are determined by modifications directed by the genome in accordance with conditions and due to the selection of organisms that have genotypes and phenotypes that serve them usefully under these circumstances. Therefore,

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all living organisms correspond to the geophysical and ecological conditions of the external environment through their phenomes and genomes. All types of long-term adaptation and evolution are based on changes at the molecular level. The emergence of any long-term evolutionarily significant adaptive trait is associated with preliminary changes in the molecular genetic apparatus of the cells of a given organism. Such genome modifications are directed. They can cause the synthesis of new proteins or new combinations of proteins, which can lead to the emergence of a new trait useful for adaptation in a certain population. Organisms that have successfully adapted due to this trait will also reproduce successfully and transmit this trait to new generations through the altered genome. Adaptation and subsequent evolution are based on informational processes, as they are carried out with certain interactions of a living body with environmental factors. Any changes in the material environment are perceived by the receptors of organisms as specific information signals. Firstly, the functional systems become activated to prevent or compensate for the action of unfavorable factors. However, if the effect of the perturbing factor does not stop and it continues to act, then those principles of adaptation that are most adequate to these conditions will gradually be generated and fixed in the genome. Thus, the survival of organisms in changing environmental conditions that are not always favorable is also ensured by their ability to adapt. Adaptation of the “phenotypic framework of a genome” is one of the main properties that ensures adaptation and interaction of genomes with their external environment, and is the basis for survival and the evolutionary process. Furthermore, the qualitative and quantitative composition of all living bodies on the planet, not to mention their organization, evolution, and the origin of species, can all be considered a result of the adaptation of the entire system of the global genome to changing environmental conditions in the process of development of our planet. The strategic mechanisms of survival of living bodies, their genomes, and the phenomenon of life itself are also the main factors of evolution, described in detail in Chap. 8. Heredity. Due to reproduction and heredity, parents and offspring have similar genomes and information, a similar qualitative set of cells, and the same biochemical composition of tissues, type of metabolism, functions, morphological characteristics, and many other features. That is, the standard genotype and phenotype for a given species of genome are completely inherited. Thus, the heredity of the replicating genome ensures the permanence and stability of the standard organization of species over millions of years. Genetic variation. The mechanism of inherited variation of genomes determines the emergence of new hereditary information and properties in organisms, and their transmission to future generations (see Sect. 8.4). This contributes to the diversity, adaptation, resilience, and survival of both the species of living bodies and their genomes. Various processes of recombination of genetic material occur during reproduction or in the process of mutations. This is of great strategic importance, since it contributes to the emergence and consolidation of new information in the genome,

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which enables the formation of new variants of daughter genotypes and phenotypes that can integrate into new living conditions. Selection. Rigorous natural selection of genomes goes through the selection of phenomes by factors of the natural environment, ensuring the preservation and selective reproduction of only those organisms with traits that are useful for particular conditions and the elimination of less well adapted representatives. That is, natural selection leaves only viable variants of living bodies, and along with them, the genomes that carry useful genetic information. This mechanism allows for the global evolution, adaptation, and survival of organisms over billions of years in accordance with the changing nature of habitats on Earth. Evolution of the genetic information in genomes ensures that species of living organisms overcome the pressure of entropy and the adverse effect of changes in habitat conditions. However, new variants of cells and living bodies that arise on Earth do not persist forever, but only as long as there are environmental conditions that satisfy their vital needs. The fact is that the adaptations of organisms created by evolution are imperfect in time and the pressure of omnipotent entropy eventually overcomes them. Therefore, the evolution of taxa is inevitable. Species of organisms and their genomes appear, live, develop, and in the end, are modified into forms that are better adapted to the changing situation, or disappear as a result of the impossibility of surviving in new conditions, or are supplanted by stronger species. Consequently, it is the evolutionary strategy that ensures the adaptation and survival of living bodies and the very phenomenon of life on such a changeable planet as our own.

12.4 Hypobiosis and Anabiosis The temperature of life for the vast majority of organisms lies within the range between 0 and 90 °C (Sect. 1.8). Higher temperatures irreversibly destroy the molecules of life, viz., DNA and proteins, and the hardening of water stops metabolism and functions. A significant inhibition of metabolism and the cessation of vital activity are also observed when organisms are dehydrated, since sufficiently active movement of molecules and the course of biochemical processes are impossible when there is a lack of water. Hence, life processes proceed at different rates depending on the temperature and availability of water. Many living bodies use this property for strategic survival under adverse conditions. Depending on the presence of manifestations of the signs of life, such states of organisms are conventionally classified as hypobiosis, which refers to suppressed but reversible vital activity, and anabiosis, meaning a complete but reversible cessation of life processes. Hypobiosis. With seasonal or sudden changes in living conditions, for example, in the absence of food or water, or when the temperature drops below 0 °C, organisms can go into a state of hypobiosis, which is characterized by acute suppression of

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motion, nutrition, respiration, excretion, and other signs of life. Examples of hypobiosis are cold torpor of many amphibians and reptiles, as well as hibernation in rodents. In this state, the temperature of their bodies can drop down to 0 °C for quite a long time. In such a state, other programs for the implementation of genetic information are switched on in such animals, and other systems of genes of the same genome begin to work. They transfer the metabolism of animals to another level and ensure the processes necessary for their adaptation and existence under other conditions. Such animals become active again and return to the standard genetic life support programs after the restoration of the normal temperature range. Some organisms have the ability to withstand deep and prolonged dehydration while retaining the ability to repeatedly restore vital activity when water becomes available. This phenomenon is inherent in some microorganisms, plants, and invertebrates. The water content can drop to 1–3%, which is not enough for biochemical processes to take place. Life processes in such organisms can stop almost completely for a long time, but recover when water is supplied again. Anabiosis. This is the complete cessation of all manifestations of life due to such environmental factors as deep freezing, deep dehydration, or a combination of both. This phenomenon is typical mainly for some microorganisms, plants, and simple animals (for example, rotifers, barnacles, and tardigrades). Some species of amphibians and reptiles can also endure freezing for several months in the winter season. Bacteria which have existed in a state of anabiosis for tens of thousands of years have been extracted from a depth of several thousand meters under the ice of Antarctica and revived in the laboratory. Spores and cysts of microorganisms, algae, and fungi, and also seeds of plants, are other life forms that can be in a state of suspended animation for a long time. This enables preservation and even the dissemination of life, despite the presence of unfavorable environmental factors. Conditions for anabiosis can be artificially created in the laboratory. Various biological objects can be cryopreserved (frozen) down to the temperatures of liquid nitrogen (–196 °C) and subsequently manifest no vital signs for many years. Efficient cryopreservation protocols have been developed for spermatozoa, erythrocytes, bone marrow cells, embryos of various animals at early stages of development, pieces of tissue, etc. The structure and vital activity of such entities are revived after thawing, and they can be used, for example, for research purposes or biomedical applications. The basis for the ability of biological entities to undergo anabiosis is the property of nucleic acids and proteins to retain their structure and functions after warming, even from a prolonged state of deep freezing and complete dehydration. Thus, life processes can proceed at different rates, and they can be strongly inhibited and even reversibly terminated, thereby providing a strategy for survival in the most unfavorable conditions. Moreover, the life of the genome, “conserved” by the cold, can retain its vital potential for many millions of years, not only on Earth, but also on other astronomical objects.

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12.5 The Purpose of the Lives of Individuals Life as a phenomenon has existed continuously on Earth for several billion years, despite the fact that all organisms are mortal and live only for a short time. As noted earlier (see Sects. 1.10 and 2.4), living bodies are dissipative systems that are constantly being disintegrated, primarily by thermal motion, which leads to an increase in their entropy. Organisms could not exist at all if they did not constantly fight against natural destruction by engaging in the constant synthesis and replacement of worn out parts that make up living systems. This is done by absorbing, processing, and using matter and energy from the environment. For example, proteins, polysaccharides, lipids, ATP, and so on, are constantly degraded and resynthesized in cells. Membranes and organelles are destroyed and restored. In addition, multicellular organisms also constantly renew their cellular composition. The strategy behind such behavior is to focus on surviving (see Chap. 10) long enough to reproduce (see Chap. 9) in the interests of the planetary system of life. Organisms live for the allotted time in a rather aggressive environment. For example, all terrestrial organisms contain up to 75% water, but they live in a waterless airspace. Individuals can live in freezing temperatures, in arid deserts, in hot springs, and so on. To survive in such conditions, they must have special adaptations. But, in spite of various ingenious solutions, no living body is absolutely perfectly adapted in our constantly changing world. Moreover, for self-preservation and survival, any individual must first of all withstand competition for food, and protect itself from adverse environmental factors like cold, heat, drought, radiation, etc., or avoid them. Living organisms need to continually acquire nutrition, which ensures the supply of the necessary substances for plastic processes, the constant renewal of the molecular composition of cells, and the maintenance of integrity. Nutrition also provides substrates for cells to convert and use energy. Food may not always be readily available and not always in sufficient quantities. Therefore, many organisms have to make significant efforts and withstand fierce competition in order to survive. It is also necessary to avoid enemies. In such extreme conditions, it is mainly the strongest representatives who survive, and the weak, defective representatives who are eliminated. This is indeed the mechanism of natural selection. Thus, all representatives of the living world have to constantly and instinctively fight for their lives, for survival. However, we note that the main character of any organism is the genome. As noted above, individuals are only carriers of the genome. They are the phenotypic framework of their species of genome. It is the genome that regulates its environment through transcription and translation, i.e., the internal and external environment, providing itself with favorable conditions in extreme surroundings. Thus, the struggle for the survival of cells and organisms is an illusion. In fact, the real purpose is to ensure the survival of their own genome. Each organism is programmed by nature for reproduction. This is essential, but it does not serve the living bodies themselves. It serves the system of genomes of its species and, ultimately, the immortal planetary system of life. Without realizing this,

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for a significant amount of the time not associated with physical survival, individuals instinctively search for a sexual partner or accomplish other processes associated with reproduction, as programmed by their genomes. Great competition also exists in this crucial process, which leads to the selection of mainly the youngest and strongest producers with high-quality genomes. The healthy genomes of the parents ensure the emergence of sterling offspring that will survive and pass the permanent genome on into the future. The average lifespan of a distinct species of living organisms on Earth is approximately several million years. The average lifespan of individuals varies significantly: from 20 min (the bacterium Escherichia coli) to 5–7 thousand years (the long-living pine tree Pinus longaeva). Consequently, the lifespan of an individual is much shorter than the existence of its species. The basis for such a long existence of species is the ability of individuals to transfer the hereditary information of genomes from generation to generation. This is realized in the process of reproduction, which results in the transfer of a full set of genes and tools for their use, inherent in the organisms of a given species, to daughter organisms. Genetic information is used in the development of individuals to accurately recreate all the details of the appropriate structure and allow the possibility for the appearance of new variants of the characteristics of the organism. Thus, new individuals are constantly emerging to replace those that have perished, and some of them have new characteristics. This strategy allows the species of genomes, and indeed the entire planetary system of life, to exist for a very long time, and besides, to gradually evolve, spread, and adapt to new conditions. Such behavior of living bodies is based on internal, genetically determined motives and is conditioned by two basic instincts—to survive and to reproduce. Moreover, the aspiration for survival serves the living body itself and its genome, while the aspiration and desire for reproduction serves only its genome and the planetary system of life. That is, the strategic purpose of any individual life is the inevitable provision of the ability to survive and reproduce, primarily for the benefit of its genome.

12.6 The Strategy of Monolithic Coexistence The tactical and strategic means of survival discussed above allow living bodies and their systems to exist for a sufficient period of time to accomplish reliable reproduction of the permanent genomes traveling through space and time, and thus also the survival of their planetary system. Once again, we emphasize the hidden, but highly successful strategy of the joint monolithic existence of genomes and their bodies: A. Living bodies belong to the moment. • Organisms do not need to reproduce to live, but they live to reproduce genomes.

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• Organisms do not need to evolve to live, but they live and reproduce in order for their genomes to evolve. • Organisms do not need heredity to live, but they live and reproduce in order to transmit organizational standards through genomes. • Organisms do not need genetic variation to survive their time, but they live and reproduce in order to allow their genomes to evolve. B. Genomes belong to eternity. • Genomes need to multiply in order to exist forever and maintain a permanent planetary system of life. • Genomes need to evolve in order to survive and for the system of life to exist forever. • Genomes need heredity in order to transmit precisely the standards of organization of their species, and to maintain their taxa and the planetary system of life. • Genomes need genetic variation in order to survive and adapt their phenomes to the joint evolution of planet Earth and the phenomenon of life. Thus, only the monolithic coexistence in a single living body of the genome as cause and the phenome as effect allows the phenomenon of life to achieve eternal existence.

12.7 Summary Living organisms are highly organized, ordered, integral heterogeneous physicochemical systems that exist for a long time in a relatively stable state in a not very favorable environment, despite the constant wear and degradation of their individual elements. The ability to maintain an ordered state and the integrity of the body through self-repair ensures its autonomy, survival, and long-term existence under conditions of dissipation in an unstable environment. That is, the main condition for the long lives of cells and organisms, their integrity, and the maintenance of homeostasis and a high degree of order is the constant controlled renewal of the corresponding molecular and cellular structure and composition, along with various regeneration processes. As a result, intracellular and organismal homeostasis maintain a constant comfortable environment for the core element of life—the genome. The survival tactics of individual organisms are based on adaptation, the maintenance of integrity, and homeostasis. The strategic mechanisms for the survival of individuals and the planetary system of life are based on the continuous reproduction of genomes and their bodies, but also on evolution and the ability to survive threats to life through suspended animation.

Part VIII

Power of the Genome

Chapter 13

Cognitiveness of Living Bodies

13.1 Information and Control Principles Information is a fundamental category, but difficult to define. Generally, information is defined as a collection of data that can be generated, transmitted, accumulated, perceived, and used. Information itself is immaterial, but it is a property of matter, such as, e.g., discreteness and motion. Any objects, phenomena, or events that can generate a variety of interactions and states of an innumerable set of elements of nature can be the carriers of information. In other words, information is a variety of fluctuations of the surrounding space. Any changes to any measurement are sources of information. Information can exist and be transmitted in the form of various material carriers: atoms, molecules, aperiodic polymers, objects, fields, waves, vibrations, particle flows, etc. It can also exist and be transmitted in the form of numbers, letters, ideas, thoughts, fantasies, images, signs, pictures, the contents of books, computer programs, etc., so it is a product of matter, but not of a material nature. Cybernetic systems. The science of managing, communicating, and processing information is called cybernetics. It studies the general properties of various control systems, regardless of their material basis. Such properties are characteristic of biological objects, various societies, and various technical systems. The main subject of the study of cybernetics is information. Various phenomena or events can be sources of semantic information, often constituting signals for an action. For example, hormone molecules are perceived as a signal by cells that have special binding receptors for it. The cells respond to the incoming command by activating certain processes, for example, the synthesis of ATP. Cybernetic systems are organized and ordered sets of interconnected and interacting elements capable of perceiving, recording, and processing information, as well as exchanging it with each other and with the external environment. Many cybernetic systems have cognitive properties. Such systems include both living objects (cells, organisms, communities of organisms) and programmable machines, computers, etc.

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Cognitiveness is the ability of systems to perceive, process, and operate with information. On this basis, the system is oriented in space and time, the current situation is “cognized”, goals are set, and reasonable decisions about how to act in a particular situation are carried out. Cognitive systems vary in their complexity and level of organization. The complexity of such a system depends on the number of elements, on their thesaurus, programs, and memory, on the device, on the variety of internal connections between the structural elements, etc. The details of the work of the most complex cybernetic systems created by man (computers, robots, space flight control centers, etc.) are well known. However, living bodies created by nature are still far from being fully studied and understood due to the enormous number of different elements in their constituent systems, the diverse connections between them, and their complex hierarchical organization. In many cases, the same component may be part of several units or systems. For example, extremely complex multicellular organisms are controlled by the brain, which is an independent complex system consisting of billions of equally complex cells. The functional unit of the brain is the neuron—an extremely complex, independently functioning cybernetic cognitive system, with a huge number of different connections and very complex internal molecular organization. Biological systems are probabilistic; the options for their behavior are difficult to determine due to the impossibility of accurately predicting the interactions and reactions of the diverse components of their subsystems, which are simultaneously affected by a colossal variety of physical and chemical factors. A cybernetic system is defined as closed if its elements exchange signals only among themselves. Open systems, such as living organisms, necessarily exchange information with the external environment. For example, animals have complex systems of analyzers: visual, auditory, tactile, vestibular, etc. Each analyzer is itself a complex system that includes a number of basic elements. In particular, these are receptors—special cells, or specially arranged nerve endings, or modified nerve cells located in various parts of the body. They are usually able to perceive only a certain kind of stimulus. The modified nerve cells of the retina are sensitive only to electromagnetic radiation of a certain wavelength. Merkel cells, connected to nerve endings, are specialized receptors of the somatosensory system. They react only to mechanical stress. Once perceived by receptors, information, regardless of its nature, is converted into an electric current (translated into the universal language of living bodies), which is transmitted through the nerve processes (the conductive part of an analyzer) to afferent neutrons. This is the analyzing center, the main link in the analyzer system. The incoming information is processed here and converted into a specific electrical signal, which is further transmitted to the efferent neuron. This neuron also generates a suitable electrical signal in accordance with the incoming information. It propagates along the nerve processes to the effector organs, which respond accordingly to the received signal with a specific action. For example, the secretion of a hormone, contraction, secretion, enhancement, or suppression of various processes and functions. Complex cybernetic cognitive systems, including cells and organisms, have the ability to store and accumulate information that can be used at a later point in time.

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This property is called memory. Memorization is conventionally achieved in two ways: (a) due to a change in the state of the system’s elements; (b) as a result of a change in their structure. In particular, a huge amount of information about the development, organization, and functioning of various cells and multicellular organisms is recorded by means of a specially ordered structure of DNA molecules. In the process of expression (changing the state of the elements of the system), information is built into certain features that determine the characteristics of the system. Due to changes in the state of the elements of the system, animal brains can accumulate and store a huge amount of information used for survival, functioning, and reproduction. In addition, on the basis of memory, animals are capable of learning. Furthermore, humanity has progressed as far as learning to record huge amounts of information on artificial media, enabling its long-term storage and transmission to subsequent generations. Transmission of information in the form of signals is carried out via communication channels. A communication channel is the medium through which signals are transmitted. In the nervous regulation of muscle contraction, the signal is an electrical nerve impulse, and the communication channel is the axon membrane. Physical carriers of signals can be various features of the material world: molecules, electromagnetic radiation, mechanical action, mechanical vibrations, electrical impulses, gravitation, etc. Moreover, one form of signal can be transformed into another in the process of transmitting and processing information. For example, the energy of photons of visible light in the retina of the eye is converted into electrical impulses, which are transformed in the nerve endings of brain neurons into molecules of mediators of the nervous system. These molecules act on the membranes of certain neurons, again causing an electric current which circulates in a certain part of the cerebral cortex, producing certain visual images. To ensure an adequate response by a given system, distortion of information should be eliminated in the process of perception, transmission, and processing. This phenomenon of signal–response correspondence is called isomorphism. Violation of isomorphism leads to inappropriate responses by the cognitive system. Depending on the characteristics of reaction of a given system, signals can be informative (convey information) and executive (convey a command to action). In particular, through vision, we receive mainly informative signals, whereas for example, hormone molecules convey a command for action to the target organs. Signals of different nature will have a definite informational effect only in the presence of special receptors. For example, there are special receptors for hormones, but only in target cells. The rest of the cells remain insensitive to this signal. External signals can also be captured only by the corresponding organs or special cells. For example, the eyes are adapted for perception of a certain range of electromagnetic waves, and the ears for vibrations of a certain frequency. Hence, living organisms do not perceive the huge total amount of information that is potentially available, since they lack the necessary receptors. In particular, animals are generally “blind” to magnetic fields, neutrino fluxes, various microwave oscillations, X-rays, and ionizing radiation (although some of these can have a direct impact on the components of living systems). Yet, some organisms do possess the unique and amazing ability to sense

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certain signals that are invisible to us, including a variety of electromagnetic fields, as well as to see and hear far outside the range of human perception. Animals are among the most intricate “antennas” in the world, tuned to a whole range of different signals. Through a variety of sensor organs and receptors, they capture a huge variety of information. Tiny amounts of information of different kinds are amplified by several orders of magnitude and converted into energy, setting in motion cells, systems, body parts, and the entire organism. In addition, humans have learned to progressively increase their “antenna capabilities” using special devices and methods. With the help of an electron microscope, our visual acuity is increased by a factor of a million, so we can examine the inner contents of cells with the same ease as we do the landscape through the window, and the James Webb Space Telescope allows humanity to look far into the confines of the Universe. Furthermore, humans have learned to visualize and perceive information that is not even natural for us and for which we have no direct receptors. For example, information obtained using X-rays is applied in experimental physics, chemistry, and biology, for diagnostics in medicine, etc. Ultrasonic sensors serve humanity to obtain a mass of useful information through special devices that emit, perceive, and demonstrate various processes. Likewise, humans exploit thermal radiation, gravity, neutron fluxes, neutrinos, and other sources of information that are not natural for us. Moreover, not possessing receptors and analyzers corresponding to these flows of matter, people are able to transform physical sources of information into means and images that are easily perceived by their standard senses. For instance, X-rays leave visible marks on a special film and the molecular composition of blood can be visualized on paper using electrophoretic or chromatographic techniques. Any message consists of a combination of simple signals. The complete set of such signals can be called an alphabet. A separate signal is a letter. In particular, the set of four nitrogenous bases of DNA (adenine, guanine, thymine, and cytosine) form the alphabet for encoding genetic information, and individual bases are the letters of the genetic code (A, G, T, C). The sequence of three bases (triplet) of a structural gene encodes one specific amino acid. For example, AUG encodes methionine. The sequence of triplets encodes the primary structure of a particular protein. The encoding process is the recording of a message using the alphabet. Translation of this message into another alphabet is called transcoding, and complete decryption of the message is called decoding. For example, translation (the formation of a specific polypeptide on an RNA matrix) is transcoding, and expression (manifestation of the properties of proteins) is decoding. The phenomenon of coding enables the use of a small alphabet to store and transmit large amounts of information. For example, computer technology uses a digital binary code language with only two characters (0 and 1), and the amount of encoded information used is simply colossal (for instance, the Internet!). The biological language uses a quaternary code with four characters A, G, T, and C, meaning that it has to be more compact to record a huge amount of information in the small volume of a genome. Perception, transformation, and transmission of information are associated with the expenditure of energy. Deterioration of the energy metabolism of cells leads

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immediately to disturbances in the processes of gene expression, as well as disturbances in the reception and transmission of signals from the internal and external environment. In higher animals, energy disturbances, for example, to neurons, can lead to pathologies of the nervous system and many other functions due to errors in the processing and transmission of information. Control is required to purposefully change the properties and functions of the cybernetic system. Control is a specific informational influence that brings about a standard programmed reaction of the cognitive system, leading to the achievement of the desired goal. The essence of programmed control is the setting in motion and interaction of significant masses of substances, as well as the transfer and transformation of large amounts of energy, controlled and directed by the small amounts of substances or energy that actually carry the information. Informational control processes are typical for the operation of any cybernetic system. This can be the transfer of hereditary traits in biological systems, management of collectives, management of machines, conveyors, etc. The control principles are the same for objects of various kinds and complexities, from the regulation of molecular processes in cells and various functions in organisms to the principles of computers and spacecraft control. Any control system consists of a governing body, a control object, and a communication channel between them. The governing body processes the available information and develops a command action. It is transmitted through the appropriate channels to the control object. Communication is carried out through physical and chemical processes that carry information. Having received the signal, the system goes into the required state. For example, the human brain receives a mass of information every second through thousands of different external and internal receptors, processes it consciously and unconsciously, and generates a command which propagates along axons in the form of electrical nerve impulses to control objects, such as the muscles of the arms or legs, endocrine organs, or other parts of the body. As a result, the organism transits into a qualitatively different state and an action is taken to achieve a certain goal. Cybernetic computer systems can be controlled without human intervention, in accordance with a certain pre-assigned program, and in living organisms, many processes are regulated unconsciously. This option is called automatic control. In living organisms, thousands of different biochemical and physiological parameters are automatically monitored and regulated, such as the amount of water in cells and tissues, the ionic and cellular composition of the blood, heart rate, blood pressure, the electrical potential of cells, the amount of ATP that has been formed, digestion of food, the formation of urine, and much more. This enables automatic maintenance of the constancy of the internal environment in living cybernetic systems (homeostasis), which is an indispensable condition for the stable operation of the system, even under changing conditions. The most widespread and effective systems for maintaining homeostasis are closed-loop control systems with feedback. In this case, the control system processes information received from the outside, as well as from other parts of the system, and it also receives signals from the controlled object via the feedback channel. Feedback is the transfer of information from a controlled object to a governing body. Feedback

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can be positive or negative. With a positive feedback loop, the signal enhances the process, causing the system to transit to a new level or triggering a cascade-like process, whereas a negative feedback loop slows down and stabilizes the process, preventing its further development. Negative feedback systems are self-regulating. Living organisms are feedback cybernetic systems, that is, they have the ability to self-control and self-regulate. This can be traced at all levels of organization in living bodies. At the molecular level, for example, molecules of the products of enzymatic processes, upon reaching a certain concentration, inhibit the work of enzymes that catalyze this process. Such enzymes, in addition to the substrate center, have a special center for allosteric regulation by the products of biochemical processes. The concentration of all molecules inside the cells is maintained at a constant optimal level, which is also regulated according to the feedback principle. The amount of hormones synthesized by the cells of endocrine organs is controlled by the action of the same molecules contained in the blood. Constant body temperature in mammals is regulated at several levels based on feedback through special receptors and a variety of organs. Thus, living bodies are extremely complex cybernetic systems that operate through the “cognition” of circumstances and “decision-making” based on external and internal information.

13.2 Informativeness of Matter Any law of nature is a complex of information about the properties of certain material bodies, systems, and processes. Each material body contains a certain amount of information. Naturally interacting elementary particles, atoms, molecules, or other elements of systems form bonds and transit into different states, creating and accumulating new information. When they examine objects and their properties, scientists reveal the information contained in them, establishing various kinds of patterns. The same applies to the dynamics of physical and chemical transformations of substances. Any transformation is associated, not only with the alterations of matter and energy, but also with changes in information. For example, not only do material transformations DNA → RNA → protein occur in biochemical reactions of protein synthesis in cells, but so also the information recorded in genes is modified, transferred to other carriers, and then used to form polypeptides. Information cannot exist without a material carrier. Any information, any complex of knowledge, reflex, or thought, is associated with matter and material processes. All material bodies and fields are carriers of information. It is contained in them in a similar way to potential energy. Just like potential energy, it can be either manifested or not. Information manifests itself as various fluctuations of the natural environment: in the form of waves, vibrations, or motions of bodies, molecules, atoms, etc. As a part of nature, information has many different levels of organization: at the level of the Universe, galaxies, stellar systems, planets, physical bodies on planets, molecules, atoms, elementary particles. The world around us contains a tremendous

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amount of information, some of which we humans have already discovered. Living organisms on the planet Earth are a drop in the ocean compared with all the matter in the Universe. But this is a qualitatively specific state of matter. Living bodies possess a number of unique properties and mechanisms (see Chaps. 6 and 7). Another difference from non-living bodies is that living bodies have many more levels of order and organization, which means they have much more accumulated information. They include all the information from the lowest levels of organization, starting with elementary particles, atoms, and molecules. The next level of organization is the formation of DNA and RNA macromolecules. These are the stem molecules of life (Sect. 1.5, Figs. 13.1 and 14.1). This is a level at which there is an extremely high “informatization” of matter. These are polymer molecules with aperiodic ordering of the structure and alternation of monomers. That is, they have a “language”, a specific arrangement of nucleotides, in which the order of alternation accumulates and records a huge array of information, sufficient to create many millions of species of organisms, involving hundreds of thousands of different proteins. This is already the next level of “informatization” of matter. Proteins (see Sect. 1.6) possess not only aperiodic linear information in their amino acid sequences, but also spatial information. This is information on their surface (features of size, shape, charge, etc.), which determines the recognition and regular interaction of various molecules, as well as internal information (regulatory centers, catalytic centers, functional groups of atoms, mobile segments, etc.), which specifies countless functions and properties of proteins. This aggregate of information, along with the mechanisms of synergetics, is the basis for the construction of supramolecular complexes: biological membranes, enzymatic complexes, and organelles. These structures can be considered as another level of “informatization” of living matter. Organelles are built on the basis of all the previously mentioned information, and in this sense accumulate this information. Cells are highly ordered, heterogeneous open systems. They consist of regularly arranged atoms, molecules, macromolecules, and organelles. These systems are formed on the basis of the above-mentioned complex of information, under the control of the genome. They contain all the above-mentioned information, as a standard for a specially modified material space.

13.3 Biothesaurus It should be noted that information manifests itself only to an entity capable of perceiving it. The principles of the theory of semantic information, characteristic of biosystems, were laid down in the 1970s. The basis of this theory was not just the idea of a code and a transmission channel, but also the properties of the receiver that perceives the information, as well as the assessment of its semantic meaning. The main concept is that the semantic information perceived by a given living system can be assessed only relative to the information that that system has previously accumulated. That is, in order to adequately perceive information from external sources, the biosystem must itself already have a certain minimum stock of knowledge. The

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Fig. 13.1 The “bioinformation explosion” is the basis for the development and dissemination of life. Such an information explosion, which orders matter, occurs during reproduction and development. Its mechanism is an ultra-high-rate chain reaction of replication of DNA molecules

minimum store of information in a biosystem is referred to as its biothesaurus, by analogy with the term thesaurus, which is used in information theory to denote the total of all the information that a subject possesses. The presence of an initial biothesaurus is a prerequisite for the assimilation and accumulation of external and internal information by biosystems. In the process of perceiving information, systems react by changing their state and implementing potential properties and functions. The perception of information also contributes to the development and improvement of such “intelligent” systems. Moreover, the efficiency of information exchange is determined by the properties of the receiver of information, not its source. Biosystems at any level of organization are sources of various signals that carry information about the organization and its functions. But these signals can be perceived as meaningful information only by those systems that understand it, that is, those that have a certain thesaurus. This means that, among living organisms, information is transmitted according to the “everything to everyone” principle, but is perceived according to the principle “to whom it may concern”, namely by the systems capable of perceiving and understanding it. Information arises (it is better to say, manifests itself) only with the appearance of entities or systems that have special receptors and mechanisms to perceive it, and also possess a certain thesaurus. Semantic information arose with the emergence of living systems, which began to use it purposefully with the application of a biothesaurus for self-preservation and survival. The accumulation of information and the improvement of the thesaurus led to the gradual development of living bodies and their evolution. Features of environmental factors (features of the quality and quantity of external information) determined the specificity of the formation of thesauri of living bodies inhabiting under certain conditions, which ensured the direction of their development. This was one of the conditions for the appearance of species diversity.

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The biothesaurus system is the system of knowledge and skills of any living body, specific for each species, but having the same organization principle. It consists of subsystems of information storage, information perception, information recognition, and response. The thesaurus of cells is primarily represented by the genome, where genetic information is stored and processed, but also by the system of molecular mediators of its interactions with the inner and outer world. Various receptors, physicochemical systems for processing signals, and response-forming systems belong to the phenomic part of the structure of the cell’s thesaurus. The biothesaurus works on the basis of the aggregate information from different receptors and reacts with standard responses in accordance with the genetic programs stored in the genome. The concept of a genetic program is a specific plan for a clear sequence of actions recorded in certain genes of a given genome. Genetic programs are realized with the help of special molecular mechanisms of transcription, translation, selective catalysis, etc., which successively unfold in time, forming a strictly conditioned process that leads to the formation of a specific structure and function. For example, these are the programs for growth and development of a body, programs for the structural and functional organization of certain organs, programs for behavior, and so on. Thus, all manifestations of life are associated for a certain time with the existence of highly organized, integral, hierarchical systems of molecules and cells—living bodies formed and supported by the genetic programs of genomes. Genetic programs are very rigid. These are the rules for the unquestioning behavior of biological systems. Figuratively speaking, it is a “code” or “constitution” for the behavior of all components of the given biosystem. Molecules move and transform in metabolic chains and metabolic cycles, strictly following genetically determined protein pathways. Any alternatives are virtually impossible. Cells divide, grow, and interact through genetically determined mechanisms. Organisms grow, function, and multiply in a certain information space of the external environment and under the control of genetic information and genetically determined mechanisms. From this point of view, living bodies are products of the interaction of genetic programs and information from the surrounding space. Thus, the main properties of the living are determined by genetic programs of the genome, as well as the cognitive ability of living systems with a biothesaurus to generate, transmit, perceive, process, and apply information. This is a fundamentally new ability that determines the stability of living bodies in their thermodynamic disequilibrium.

13.4 Entropy and Information There is a direct connection between information and entropy. From the point of view of thermodynamics, a developing living organism is an open system, the negentropy (orderliness) of which increases with time, depending on the increase in used and

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accumulated information. This makes it possible to improve and complicate the structure, as well as to perform increasingly complicated work processes. It is also one of the distinctive properties of living bodies to use information to reduce entropy. This is clearly manifested during the various stages of their development. However, maturation is followed by aging, associated with the gradual destruction of the body, that is, an increase in entropy. This means that living bodies are characterized by an initial decrease in entropy in the process of growth and development, followed by its decrease in the process of aging (Fig. 11.3). Note again that living bodies are built, live, and survive on the basis of information. In living organisms, each level of organization corresponds to its own flow of information. That is, cells are constructed on the basis of genetic information, tissues are made up of cells, and organs are composed of tissues, which taken together make up an organism. The molecular level of generation and distribution of information is key here. This primarily applies to nucleic acid and protein molecules. In particular, the “information explosion” of a specific genome during replication (Fig. 13.1) and the subsequent processes of transcription and translation trigger a rapid cascade of successive transformations of matter and information at the moment of reproduction, which ultimately leads to the creation of a huge number of cells, and then complete living bodies. Organization and orderliness (negentropy) of a multicellular body, for example a chicken (Fig. 13.2), are gradually created by the development process from the disordered contents of the surrounding material space, viz., an egg, on the basis of information in genetic programs contained in a zygote. Furthermore, the entropy of this closed system only decreases with time as the genetic information is used.

Fig. 13.2 A miraculous transformation of matter and information takes place in a confined space in less than 400 h. A complex organism is built from a chaotic set of organic molecules and water on the basis of genetic programs. In a confined space, 40 g of inanimate, unorganized colloidal matter, which does not exhibit most of the properties of life, turns into practically the same 40 g of a living, organized system of cells, organs, and tissues. Such an organism is capable of independent movement and nutrition, and is determined to certain functions and behavior. The center of organization for this fantastic transformation is the tiny genome contained in a zygote

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13.5 Information and Levels of Development A cell is a system of interacting molecules. This implies an extraordinary dynamic not only of matter and energy, but also of information. Only the necessary molecules are synthesized and transformed, and this is prescribed by genetic information. Only the necessary molecules enter or exit the cells, and this is determined by the informative “awareness” of the membranes. Molecules interact with each other on the basis of their linear and volumetric information. Enzymes created by DNA molecules determine the strict ordering of molecular processes. Examples are the synthesis of specific proteins, the breakdown of glucose, the oxidation of tricarboxylic acids, and many others. All the above processes involve the use and transformation of a variety of information flows. From this point of view, cell metabolism can be seen as strictly directed, interconnected, interacting flows, not only of matter and energy, but also of information. Multicellular organisms include all the general information mentioned above, and in addition, a huge amount of information inherent only to them. This is due to the regularities in the structure and organization of various highly complex living bodies, the presence of various organs, tissues, and body parts, not to mention thousands of different cells. Millions of species of living organisms possess thousands of different functions. This contains a huge amount of information. Thus, the level of organization of living bodies is determined by both the quality and the amount of information used to construct them. In particular, primitive unicellular organisms and bacteria have the smallest genomes, while more complex multicellular organisms have larger ones. The stage of development and complexity of organisms is also determined by the quality and amount of information they are able to perceive, analyze, use, and generate. Animals, especially highly organized ones, are able to perceive and analyze enormous flows of information. For this purpose, they have a variety of senses (smell, touch, sight, hearing, etc.). Some animals have organs that sense ultrasound, electromagnetic radiation, and electric fields. Some have the ability to sense and navigate in magnetic fields, and to sense radioactive radiation. Plants have photosensitivity, and they have the ability to perceive temperature fluctuations and determine the season. As already noted, all living bodies have a variously developed system of perception and analysis of semantic information, which we call a biothesaurus. Perceiving one kind of information or another with the help of special receptors and analyzers, living bodies are perfectly able to orient themselves in the surrounding space and time. They avoid unfavorable factors, choose the best time for reproduction and growth, find food and sexual partners, etc. All this ensures the main goal of life: survival. Most living organisms are able to specifically generate and distribute various signals (information) around them. In this way, they can contact and interact with each other, even over long distances. This is very important for survival, reproduction, and the maintenance of genetic continuity. In addition, all living organisms involve massive internal flows of information.

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Hence, the ability to create, perceive, accumulate, process, and use information is among the most important components of life. The greater their ability, the higher the position of the organism in the biological hierarchy.

13.6 Living Computers Countless machines created by the mind and hands of humans are at work around us: cars, aircraft, televisions, mobile phones, computers, etc. Machines are complex devices built from structural and functional blocks that perform certain predictable actions and work. Living bodies are also autonomous, built of blocks (organelles, cells, organs), and have the ability to perform predictable actions. They have certain standards for composition, structure, and functioning. They possess certain types of behavior, standard functions, and uniform principles of work. For these reasons, we may consider organisms as peculiar, constantly working living machines. Cells are the smallest organisms, and also the structural units of multicellular bodies. In our earlier discussions (Chaps. 6 and 7), we considered them as complex mechanisms for the directed, controlled transformation of substances and energy. Now, let us look at cells by analogy with computers, as systems that also transform information. The cells of the various kingdoms of living organisms are made of essentially identical blocks and perform a set of standard actions. These miniature machines are molecular systems, as they are built from typical sets of molecules and their complexes. The work of these cell machines focuses on themselves, mainly on maintaining their own metabolism and homeostasis, as well as on their interaction with the environment. The specificity, interconnection, and purposefulness of the work of all cellular constituents is provided by the genetic programs of the DNA they contain. Moreover, since cells have a genome that controls everything, they correspond to software-controlled machines. The cell genome contains information about the composition, organization, and functioning of the system as a whole. Information is unpacked, decoded, transferred from DNA to proteins, and used to realize certain traits and properties important in the life of the cell. Numerous different molecules of structural proteins, enzymes, and their complexes are involved in the processing of genetic information. Special macromolecules transfer information from DNA to RNA and then to proteins. That is, special molecules of proteins and nucleic acids operate with genetic information! Thus, living cells are molecular operating machines, which have a clear analogy with a computer (Table 13.1). How such cellular “computers” are arranged and work is still difficult to understand in detail. However, a number of analogies and hypotheses can be made. A system unit of computers contains numerous components, the main of which are the information storage system, the processor, and parts for servicing them. A cell is analogous to a system unit.

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Table 13.1 Analogous characteristics in the organization and principles of functioning of computers and cells Feature

Computer

Cell

Information manipulation apparatus

Processor (CPU)

Genome

Basic information manipulation programs

Operating system (e.g., Windows)

The basic operating system of a cell is represented by programs for replication, transcription, and translation

Information coding system

Digital binary code

Molecular-digital nucleotide quaternary code

Unit of information

Byte

Nucleotide

Memory unit

Byte

Codon (triplet of nucleotides)

Basic elements of information

Files

Genes

Long-term memory

The entire complex of information is stored on a hard disk

The entire set of information of all DNA molecules is stored in the genotype of a cell

RAM

A set of used information and A set of used information is programs for processing it are transferred from DNA genes to transferred from the hard disk to a set of RNA the processor

Systems of extraction and analysis of information

Software programs

Gene network programs

Carriers of “harmful” information

Computer viruses

DNA and RNA viruses

System for visualization of information

Computer monitor

Cell phenotype

External information input system

Keyboard, mouse, various ports Cell surface apparatus

The capabilities of computers depend on the speed of the processor, as well as on the amount of RAM and long-term memory. The computer processor is a control device, one of the main parts of the operating system. The main function of processors is automatic control of the operation of a computer using programs located in the RAM. A highly organized genome is sort of processor in the cell, constituted by the set of all DNA molecules together with enzymes and regulatory proteins (special molecular information retrieval devices). Tens of thousands of genes are located in the complex structure of the genome along with various genetic programs. This is where the interactions of the genes and their selective expression are controlled, depending on the given conditions of development and the environment. The long-term memory of a computer (hard disk) corresponds to a collection of DNA molecules, where a host of information is recorded using the genetic code. The RAM is clearly analogous to the complex of RNA formed in the cell. From the DNA molecules fixed in the nucleus,

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without disturbing the structure, information is accurately extracted and translated into mobile RNA molecules, which further act in the cytoplasm. There are messenger RNAs containing information about the structure of proteins and transport RNAs that have information for the targeted binding of certain amino acids (protein monomers) to supply the ribosomes. There are also ribosomal RNAs that have information about the structure and functioning of ribosomes. The most diverse information can be “downloaded” into the RNA RAM from the DNA “hard disk”. This is used to produce a wide range of proteins that perform many different functions. All data and programs on a computer are recorded in the form of files or sets of files. Files are sections of information recorded on a carrier, for example, on magnetic or optical disks. All files in the computer memory have unique names. In biosystems, the analogs of files are genes, the main elements of genetic information. These are specific segments of DNA that determine the manifestation of various traits. Each gene also has its own unique name and location. A variety of genetic programs are recorded and stored with the help of sets of genes (genetic networks). By analogy with archived files, genes and genetic programs can also be temporarily inactivated and archived in the form of, for example, mitotic chromosomes or the gamete genome. Under appropriate conditions, the archive is unpacked and set to work. A computer software program is a sequence of instructions that are understood and processed by a computer and are intended to produce certain results. Programs define specific functions of a computer, from a simple text editor to the most complex spacecraft control programs. Genetic software programs in living “computers” are a qualitative and quantitative set of genes (files) in chromosomes (hard disks). This is a controlled sequence and pattern of expression of specific groups of genes. Implementation of the above mechanisms can lead to an infinite number of response options. In each specific case of expression of DNA genes, various groups of RNA and proteins will be formed, which leads to the emergence of all kinds of cells that have properties allowing them to perform many different functions. The set of programs for a given type of computer determines the whole range of its applications, just as the set and combinations of genetic programs determine the whole range of living organisms, along with their characteristics and properties. Hence, frogs have their own set of programs and algorithms, and cats have their own, which determines their morphological and functional individuality. An operating system is the main program (a collection of basic programs) that controls the operation of the computer as a whole. Personal computers such as an IBM PC use mainly Windows operating systems. The main set of programs available in a the DNA of a cell can claim the role of cellular operating system. These are programs such as replication, transcription, and translation, which determine the strategic properties of living bodies: metabolism, homeostasis, and reproduction. Many other programs are auxiliary, for example, synthesis of phospholipids, oxidation of glucose, and formation of ATP. The hardware of a computer is the totality of all parts, blocks, assemblies, connections, etc., made of special substances and placed in a certain order in a limited space. The hardware of a living computer is the highly organized structure of the cell. For the main part, this comprises a system of structural and functional proteins. In an

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aqueous medium, proteins form an ordered colloidal solution (gel), which has the properties of a liquid crystal. In different functional blocks of the cell (nucleus, mitochondria, cytoplasm, etc.), it has a different protein composition and different physicochemical properties, and it performs different functions. All the constituent elements move continuously in the micro-spaces of the cytoplasm, billions of molecular interactions take place, and transformations of matter, energy, and information are carried out. In general, such a protein–water matrix constitutes the hardware or material basis of the cell operating system. Computer viruses are special self-replicating programs developed by hackers. Such programs can corrupt or destroy programs and files stored in the computer’s memory. Biological viruses contain DNA or RNA and are active only in the nucleus of cells they infect. They can also be considered as “self-replicating programs” that use the material basis and the operating system of cells for their own reproduction. Moreover, they also quite often lead to gene mutations (damaged or destroyed files) in the host cell. The basic unit of computer information is a bit. A bit is a binary digit that takes the value 0 or 1. Any digital information can be encoded with a sequence of zeros and ones. Computer technology uses a binary code. It is an amazing fact that, with the help of just two characters, we can write down any amount of information! Each of the four nitrogenous bases of nucleotides which compose a molecule of DNA is a unit of genetic information. These are A, T, G, and C (adenine, thymine, guanine, and cytosine). That is, biological systems use a quaternary code. This means that, in living systems, a huge amount of information can be recorded and compactly stored in the tiny volume of a genome. The unit of memory in modern computers is the byte. Bytes are 8-bit binary numbers in the form 00,000,000, 00,000,001, …, 11,111,111. One byte is expressed in the form of 8 binary information characters, i.e., zeros and ones. The unit of memory of a cellular “computer” is a triplet, i.e., a stable combination of three nitrogenous bases, for example, ACC, TGA, GAC, AAA, CAT, etc. Each triplet (byte) encodes a specific amino acid, and the sequence of triplets in a DNA segment encodes a specific polypeptide chain. Polypeptide chains form the basis for the structure of thousands of different proteins, which independently and in different combinations determine an infinite number of traits and properties in living organisms. Thus, it is obvious that “biological computers” have their own original language, even more powerful than the language of our computers. A computer monitor is a device that allows information to be visualized on an electronic screen. For living “computers”, their bodies are a kind of “monitor”. Visualization of genetic information is manifested in the form of a phenotype, i.e., a set of external and internal traits in a given individual. For example, for a cell, these are the size, shape, number of chromosomes, nutritional characteristics, the presence of biochemical and biophysical processes, the ability to move, the presence or absence of a certain function, and much, much more. All these properties are a kind of reflection of specific genetic information. The power supply of a computer is provided externally from an external network or a built-in battery. Like any machine, cells also use energy for all kinds of activities.

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The power supply system of cells is an enzymatic system for controlled catabolism of nutrients in animals and photosynthesis in plants. The result is the transformation of energy, its storage, and its subsequent targeted use. A keyboard represents the device for inputting external information into computers, which is analogous to the surface apparatus of cells. Such apparatus contains numerous “receptor buttons”. Impacts on these buttons transmits special signals, bringing on the corresponding processes and functions. Hundreds of electrical communication channels interconnect all the computer’s different units. The program-controlled circulation of electric currents through various communication channels ensures the coordinated operation of all computer systems. Global electrical processes and interactions also take place in cells, where electrical currents run along thousands of paths and in hundreds of directions (see Sect. 7.5). Nearly all cell substances are dissociated and carry electrical charges. Any chemical transformations of substances are associated with electron and proton interactions, and displacements of electric charges. This is a controlled and coordinated movement of electric charges from one molecule to another, from one organelle to another, and from one part of the cell to another. In this way, communication and coordination between any two parts of the cell can be carried out at a colossal speed, comparable to the speed of an electric current. The most remote and negligible areas of the cell can be instantly prompted and made to react. Moreover, both the presence of certain currents and their direction can be controlled by the cell and the genome. Thus, electromagnetic processes can form a global communication system and integrate all the multi-heterogeneous components of a cell into a single structure. The system of water channels can also be considered as an intracellular communication system. Such channels, being only several H2 O molecules thick, form spontaneously around various macromolecules, around cytoskeleton filaments, and in the space of the cytoplasm structured by proteins. Moreover, several water layers form a continuous dense network connecting the internal contents into a single whole. Only certain molecules can selectively dissolve in these layers, moving rapidly and in a targeted way in the necessary direction at speeds comparable to those of diffusion in pure water. Such channels are highly dynamic and, depending on the needs of the cell, they can be disintegrated, restored, reoriented, and created anew. This ensures the dynamism and lability of the transfer of matter, energy, and information, making a structured aqueous protein matrix into a global communication system that unites everything into a single functional system. Therefore, the presented analogies indicate that cells are amazing microdevices that perfectly manage not only matter and energy, but also information, i.e., they are a kind of “living computer”. These are autonomous multilevel self-regulating cognitive systems capable, above all, of reproducing genomes, producing bodies of their own kind, and developing independently.

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13.7 Genetic Information 13.7.1 Basics of Organization and Application Living organisms are able to create and maintain a high degree of organization and grow, differentiate, and multiply according to genetic information that is stored, reproduced, and transmitted to subsequent generations via DNA molecules. They are complex systems with high levels of structural and functional organization and ordering of matter. Any such ordering of matter in biological systems arises on the basis of energy use, as well as genetic information. This is the information about the structure and functions of living organisms, embedded in DNA and received by each generation from ancestors in the form of a genome. Genetic information in living organisms is recorded in genetic material, in particular in nucleic acid molecules (Chap. 14, Fig. 14.1). In the first place, it is used in the processes of individual development. As a result, the ordered structure of living bodies is built from the disorder of molecules in the environment according to these “genetic blueprints”. Based on genetic information, free energy, and matter, biological systems are able to maintain their organization for a long time in spite of the second law of thermodynamics; they can also purposefully grow, differentiate, and multiply. The above-mentioned fundamental properties of living organisms are based on molecular information processes that take place with the participation of nucleic acids, viz., DNA and RNA, as well as proteins. This way, virtual genetic information is realized in the process of development into real phenotypic traits. The main elements of genetic information are genes, i.e., specific parts of the DNA molecule that carry information about RNA, proteins, or other molecules. These determine the development of certain traits of a cell or an organism. Chromosomal DNA contains thousands of genes that carry complete information about all proteins synthesized in cells. The set of genes of a particular organism is called its genotype. This information is encoded in DNA as a special sequence of nitrogenous bases called the genetic code (see Sect. 14.4). The specific nucleotide sequence of a gene contains information that is transcribed into mRNA and then translated on ribosomes, providing the strict order of amino acids in the polypeptide chain. The idea that information is stored in DNA and realized by transferring information to mRNA and then to proteins is considered the central dogma of molecular biology. Thus, the main law of molecular biology is the information law. In some viruses, RNA, which functions as genetic material, can synthesize a complementary copy of DNA for insertion into the genotype of the host cell. Therefore, information does not necessarily come from DNA to RNA, but can also come from RNA to DNA (reverse transcription). It is carried out with the help of enzymes called revertases. This property is applied in genetic engineering. But in the overwhelming majority of cases, genetic information recorded by a mathematically precise linear sequence of DNA nucleotides is rewritten into a linear sequence of RNA nucleotides, which is then translated into a linear sequence of amino acids in polypeptides, and then into the spatial structure of proteins. The

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resulting proteins determine the biochemical, physiological, morphological, and the many other traits of the organism which constitute its phenotype. The flow diagram of genetic information can be represented as follows: Replication

DNA −→ DNA Folding

Transcription

−→

Broadcast

RNA −→ Polypeptide

Expression

−→ Protein −→ Trait

13.7.2 Simultaneous Transformations of Matter and Information The transformation of genetic information is inextricably linked with material processes (Table 13.2). The parallels given in the table indicate the dual nature of living bodies, namely their informational and material essence. Table 13.2 The close interconnection of material and informational processes in cells Informational processes

Material processes

Replication is the process of copying genetic Synthesis of identical DNA molecules for information. Transfer of hereditary transmission to descendants. Replication is the information within one class of nucleic acids molecular basis for all types of reproduction Transcription is the process of rewriting genetic information from sections of DNA molecules to RNA molecules. Transfer of information between different classes of nucleic acids

Synthesis of complementary RNA strands from specific DNA genes

Translation is the process of translating genetic information from mRNA to polypeptides. Transfer of information from one class of molecules to another

Synthesis of linear polypeptide molecules from amino acids

Folding is the process of converting linear (two-dimensional) information into spatial (three-dimensional) information

A set of molecular processes leading to the formation of tertiary and quaternary structures of proteins

Expression is the process of realizing linear The interactions and combinations of different and spatial information in protein molecules molecules give rise to a variety of structures and functions

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13.7.3 Carriers and Information So, organisms are living carriers of information. It is also interesting to note some analogies between the properties of artificial human-made carriers, filled with files, and natural carriers, i.e., living bodies containing genetic information (Table 13.3). However, there are also fundamental differences between inanimate and living information carriers. Artificial carriers cannot reproduce on their own. They lack the necessary exchange of matter and energy with the external environment. Such carriers cannot restore their structure, and they do not have the ability to engage in natural selection and evolution. Yet, the analogies given in the table once again indicate the dual essence of living bodies, and the unity and inseparability of matter and information in them. The foregoing also testifies to the greater value of information in relation to the carrier, to the similarity of the processes of operating with information, as well as to the potential eternity of genomic information in comparison with its vulnerable material carriers, the phenomes. Table 13.3 Some analogies between the properties of artificial carriers of information (for example, flash drives or CDs) and living bodies Artificial carriers of information

Natural carriers of information—living bodies

There is no information without a carrier

There is no genetic information without a living body

The value of a piece of information can be much greater than that of its carrier

The value of the information in a genome is much greater than that of its temporary carrier, the phenome

Information can be copied multiple times and recorded to other carriers

Genetic information is replicated many times and passed on to the next generation of carriers

Information can be read selectively

Genome expression occurs selectively

Information can be manifested or not

Genetic information may or may not be expressed

Special tools and mechanisms are required to extract information from a carrier

Expression of genes requires special enzymes and cytogenetic mechanisms

Reproduction of information requires energy

Gene expression requires energy

Even slight gene mutations can lead to changes The slightest changes in the structure of a carrier lead to a modification of the reproduced in the phenotype information Information is “materialized” in the form of an Genetic information is materialized in aspects action, for example, visualized on the page of a of the phenotype book or on a monitor screen, revealed in the form of a sound, as an action of a machine, and so on

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13.7.4 Properties and Characteristics of Genetic Information Genetic information has unique properties and characteristics: 1.

2.

3.

4.

5.

6.

7.

Linearity of recording and reading information. A huge amount of information is recorded in a linear sequence of nucleotides in DNA molecules, which is then read strictly in one direction, from the 5’ end to the 3’ end, and is translated into a linear sequence of RNA polynucleotides, and then into a linear sequence of polypeptide amino acids. An enormous information content. The haploid genome of human DNA contains about 3.2 billion nucleotide sequences, which is enough to encode a million genes. In accordance with the theory of recapitulation, stating that ontogeny recapitulates phylogeny, animals store in their genomes information about the structure, processes and functions of all the phenotypes of their ancestors! Compactness of packaging. A colossal amount of information is recorded in the DNA macromolecule by means of small nucleotide molecules, indeed sufficient for the development of a huge extremely complex multicellular organism with thousands of traits. For example, in humans, this information is recorded in 46 DNA molecules (46 chromosomes) that easily fit into the microscopic nucleus of a cell, only visible under a microscope. Such compactness is made possible by special packaging processes and supercoiling of DNA molecules. Large amounts of “unnecessary” information. Of the colossal encrypted set of information, only about 5% is actually used during the period of maturity in the process of expressing certain structural genes. Large amounts of duplicated information. The genotype of most sexually reproducing living organisms is diploid, that is, it consists of two genomes, one maternal and one paternal. Each gene is represented by two copies. Therefore, if one of them mutates, the organism still retains its viability because most mutations are recessive. In addition, many important genes are represented in the genome by several copies (e.g., genes of histones and some peptide hormones). This is of great importance for stability. Some genes form repetitive tandems and clusters. Extreme stability of information. The aforementioned features of the organization of genotypes provide high storage stability for genetic material, as well as protecting it from the influence of unfavorable factors. In addition, cell nuclei contain special enzymes for repairing potential damage to DNA molecules, and this also increases the stability of information. Accuracy of information transfer. Many species of living organisms have existed on Earth for tens and hundreds of millions of years, retaining all their structural and functional traits. This means that genetic information is capable of retaining its accuracy and stability for such a long time. This phenomenon is provided by periodic rewriting and editing of DNA during replication in each reproduction cycle. In this case, genetic information is passed from one generation to another, acting as hereditary information.

13.7 Genetic Information

8.

9.

10.

11.

12.

13.

14.

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Accuracy of reproduction. The accuracy of replication, transcription, and translation is controlled by special enzymes. Many errors are corrected during the processes mentioned. If a “wrong” protein nevertheless appears, it is immediately recognized by special proteases and eliminated by splitting it into amino acids. Molecular-digital recording principle. From the point of view of cybernetics, biological systems use the molecular-digital principle of recording and reproducing information. The recording matrix is a DNA molecule, and the role of digital signs is played by the molecules of nitrogenous bases. Only two symbols are used in computer science (0 and 1), but the amount of processed information is simply colossal. Biological informatics utilizes four symbols (A, G, T, and C), which means that the volume of recorded information can be even larger. Matrix principle of information realization. The main macromolecules are constantly synthesized by cells in large quantities. These are primarily proteins and nucleic acids. The matrix principle of synthesis is used to ensure the speed and accuracy of these processes. In this case, one of the molecules or its parts serves as a template and the required molecules are “fabricated” on it, one after another. This is how complementary DNA strands are formed during replication (each of the DNA strands is a template), this is how all RNA molecules are formed during transcription (the template is a portion of one of the DNA chains), and this is how polypeptide molecules are formed during translation (the matrix is mRNA). Not only does the matrix synthesis of certain molecules occur during these processes, but the matrix principle of accurate and fast transfer of information from one carrier to another is also implemented. The catalytic mechanism for the implementation of information. Genetic information of DNA is realized in the form of traits through basic processes: transcription, translation, and expression. The aforementioned complex processes of the stepwise transfer of information are supported by dozens of special molecular catalysts called enzymes, without which the realization of this information would be impossible. Successive principle of information implementation. In the process of realizing genetic information, the products of previous stages bring about the inclusion of subsequent stages. For example, as a result of transcription, RNA molecules are formed which are necessary for the synthesis of proteins necessary for the formation of enzymes that are needed to ensure metabolism and the formation of cells necessary for forming organs and ensuring their functions. And so on and so forth. Lability of information. Genetic information is variable, which enables the appearance of new phenotypes. The causes of variability are mutations, replication and recombination errors, and the creation of new combinations during gametogenesis and fertilization. Multiple amplification of the effects of information variability in the implementation process. In the process of building a phenotype, microchanges in the genome lead to the appearance of noticeable phenotypic traits, making it possible to select single quantum events at the macrolevel.

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15. Universality of genetic information. The language and methods of recording, storing, and realizing genetic information are the same for all living organisms, from bacteria to humans. 16. Continuity of transfer of genetic information in living organisms. Stopping or disrupting the flow of genetic information leads to the death of organisms, populations, and species. 17. Integrity of genetic information. The set of chromosomes, genes, and various intergenic regions of all DNA molecules form a genome that functions as a single unit. 18. Genome information determines the characteristics of a phenome. 19. The totality of the genomes of all living bodies forms a single system, the global genome, which is a single system of circulation of genetic information— the genosphere. Circulation is carried out during reproduction, as well as by horizontal gene transfer. Thus, it is obvious that the presence of genetic information is the most important natural phenomenon determining life. The condition for its existence is molecular processes of constant interconnected circulation of matter and information in living systems. It should be emphasized that the implementation of information by the manifestations of life is made possible solely by a set of nucleic acid molecules and the molecules of unique enzymes. DNA molecules without the key enzymes would be useless, just as the appearance of biocatalysts would be impossible without the presence of the appropriate information in the genes of the DNA. What came first—matter or information?

13.8 Summary Living bodies and cells are self-regulating cognitive systems built and functioning on the basis of information that they are able to generate, perceive, process, store, use, and exchange with other systems. The genome is the basis for the existence of living bodies and the means for controlling them. This is a complex cybernetic system comprising structural and functional information that controls all the properties and functions of living bodies. This is an integral entity capable of manipulating matter and information, multiplying, and building a phenotypic framework around itself. Cells are highly ordered heterogeneous open systems formed on the basis of a complex of external and internal information. They are amazing microdevices that perfectly handle not only matter and energy, but also information. Many structures and functions of cells are organized in a similar way to computers. Cells are autonomous multilevel self-regulating systems capable of copying themselves, developing, and evolving. They are able to create and maintain a high degree of order in their organization, and also to grow, differentiate, and reproduce on the basis of

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genetic information that is stored, copied, and also transmitted to future generations through DNA molecules. In all representatives of the living world, information programs for reproduction and development are recorded in the genetic material of the genome. The presence of genetic information is the most important natural phenomenon determining life. The implementation of information by the manifestations of life is determined solely by a set of nucleic acids and the molecules of unique enzymes. Genetic information is the guiding force of life. The molecular mechanisms of the genome enable genetic information to control life by directing chaotic flows of matter and energy through functional systems, as well as by controlling the rates of these flows and the limits of their distribution. Cells and organisms are the material product of genetic information. They are built on the basis of information, exist in a dense information environment, and live and survive on the basis of the ability to generate, perceive, analyze, and use information. The processes of circulation of genetic information and biological matter pass exclusively through organisms. Consequently, living bodies can be considered, not only as carriers of information, but also as places where special information and material flows can be woven together. This demonstrates the informational-material principle of the organization of cells and living bodies. That is, any organism contains both a genetic program and its product as witnessed by its own form.

Chapter 14

Materials, Devices, and Mechanisms of the Genome

14.1 Genome 14.1.1 Repository of Information As noted earlier, the genome is the main manipulator of matter and energy (Chap. 7) and information (Sects. 13.6 and 13.7). In its conventional meaning, a genome is a collection of genetic material and information contained in the complete set of DNA in an organism’s chromosomes. This genetic information is necessary for the construction, functioning, and reproduction of organisms in a given species (see Chaps. 9 and 10). The DNA of genomes contains the following types of information: (a) on the primary structure of proteins (structural mRNA genes); (b) on the structure of mediators of protein synthesis (tRNA, rRNA genes); (c) sites of attachment of signaling molecules (to start expression, stop expression, upregulate, downregulate, repeat, etc.); (d) mobile genetic elements; (e) places of recombination, tandems, repeats, etc. Structural genes are among the most important elements of a genome. The coding part of these genes contains information about the sequence of nucleotides in RNA. The smallest genes consist of several tens of codons, for example, tRNA genes. The genes of large rRNA and mRNA macromolecules include several hundred or even several thousand nucleotides. The presence of certain genes is manifested as specific proteins in the cell or as traits of an organism. Most of the genes in a cell are in an inactive state. Only a small fraction are potentially active and can be transcribed. The quantity and quality of functioning genes depends on the tissue specificity of a cell, on the period in the life cycle, and on the stage of individual development. Functioning structural genes of an adult organism make up only around 3–5% of their total number. They directly provide information about the structure of polypeptides, and indirectly, information about the main structural and functional molecules (lipids, carbohydrates) required at a given moment in the life of an organism. Additionally, DNA is present in mitochondria, containing only a few tens of genes and other segments, but making a significant contribution to the energetics of © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_14

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organisms. These mitochondrial chromosomes, and additional chloroplast DNA in plants, are also part of the overall genome system. Thus, the genome is a single system of sequences and segments of all the DNA of a certain species of organisms. The microscopic material of a genome, utilizing the genetic code (Sect. 14.5), contains comprehensive information about all aspects of the structure and functioning of a given organism. The transit of genomic information (Sect. 9.6) and its subsequent differential expression (Sects. 10.4 and 14.6) ensure the main characteristics of life: reproduction, development, and survival.

14.1.2 Structural and Functional System However, just having information about the structure of proteins is not sufficient for development, survival, and reproduction. Further information is also needed on the regulation of gene expression in the right situation, at the right time, in the right place, and at different stages of development. In addition, the genome apparently contains information about the mechanisms of replication, compaction, and decompaction of DNA, the formation of chromosomes, the processes of synapsis, crossing over, etc. This kind of information can have a complex systemic or epigenetic nature. A genome also contains mobile elements, for example, transposons, i.e., regions of a DNA molecule that carry information about a protein involved in the rearrangement of this region, or episomes, i.e., foreign genetic sequences included in the host’s DNA and replicating along with it. There are also regulatory sites that bind signaling molecules, segments that enhance or weaken the action of genes, and a large number of elements of the genome with as yet unknown functions. This is complemented by a set of enzymes and various regulatory factors that serve the DNA (Table 14.1). Moreover, it should not be forgotten that all of this is arranged in an orderly manner in the highly organized colloidal matrix of the nucleus and cytoplasm. That is, the genome, as a structural and functional unit, comprises not only the information contained in its DNA molecules, but also the protein composition of chromatin, the features of its packing and spiralization, hundreds of enzymes and regulatory factors, and a highly organized medium (Sects. 2.6 and 3.2.1). Moreover, all the components of this system are in constant dynamics and controlled interaction. Hence, instead of the term “genome”, the term “genome system” should be used, as this more accurately reflects the essence of this highly organized structure. Thus, in our view, the genome is not only a collection of genetic material and genetic information about reproduction, construction, properties, processes, and functions of a living body, but also the most important structural and functional complex. It is a separate differentiated part of a cell, containing the corresponding complex of nucleic acids and proteins, organized into a single intricate structural and functional system. This system contains not only genetic material and information, but also material mechanisms and tools for its use. The genome is an integral entity capable of manipulating genetic information, reproducing, and building a phenome around itself.

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A phenome is also the structural and functional complex of a cell, consisting of the various elements of the cytoplasm and surface apparatus, which is a complex system constituting the phenotypic framework of a genome. This is the part of a cell that surrounds and integrates the genome into itself , forming a monolithic body. The content of the genome can be conditionally subdivided into two components that are different in purpose and function: (a) core material—genetic material represented by DNA, chromatin, and chromosomes; (b) auxiliary material—a set of proteins, enzymes, molecular complexes, and nuclear structures integrated into the organized colloid of the karyoplasm. Each cell of a multicellular creature contains one standard genome. Differential expression of the genome of an organism leads to the formation of tissues and organs, that is, it forms the shape and content of a complex living body. Consequently, a multicellular organism is a colony of differentiated genomes and their phenomes. In this way, genomes use their phenotypic framework to interact with other genomes and the environment. It is these ideas about genomes and phenomes that are implied in our book when we discuss the elusive nature of life. Let us exemplify with the structural and functional organization of the genome of a human individual. The human genome contains 3.2 × 109 nucleotide pairs, which is sufficient for encoding around a million genes. However, studies show that a human organism only contains approximately 25,000 structural genes. Furthermore, only a few percent of those are expressed in a sexually mature organism. Apparently, a significant part of the genomic information is used for the processes of embryonic development, differentiation, and growth, and is no longer expressed later. Another significant part of the “excess” DNA is contained in introns. And even more of the DNA is represented by numerous families of “meaningless” repetitive sequences. For example, repetitive sequences make up more than 50% of the genomic DNA in mammals, whereas protein-coding sequences cover only about 1%. Most likely, repetitive sequences possess as yet unknown functions. Genes involve many different peculiarities of organization. For example, some genes can be repeated many times, forming tandems (such as rRNA genes) and clusters (groups of different genes on a certain part of the chromosome, united by common functions). In particular, clusters of five different histones are repeated 10– 20 times. Certain genes of satellite DNA, for example, enhancers, usually have a regulatory or enhancing effect on structural genes. Over 95% of DNA is localized in the chromosomes of the nucleus, whereas the portion of mitochondrial DNA in the total DNA content of a cell is less than 5%. A small portion of genetic material consists of circular DNA molecules in the nucleus and cytoplasm. Human mitochondrial DNA (mtDNA) is referred to as the 25th human chromosome (22 autosomes + X + Y + mtDNA). Each cell contains hundreds of mitochondria. Mitochondrial DNA is replicated and transcribed semi-autonomously from the nuclear DNA.

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A human genome during metaphase is represented by a karyotype, which contains 46 chromosomes. Each chromosome is composed of one DNA molecule, containing a large number of genes peculiar to it. These genes are arranged in a linear order and each has its own location, its locus. Chromosomal DNA in the nucleus is subdivided into two groups depending on the nucleotide composition of the regions: (a) a group with unique sequences of nucleotide pairs that contain most of the genes and (b) a group with repeating “meaningless” sequences. Regions with repetitive sequences differ in the length of each repeat and the number of repeats. Repeats consisting of 2–8 base pairs are called microsatellites. Another group of repeats, called minisatellites, vary from 10 to 100,000 nucleotide pairs, sometimes even more. The sequences are distinguished as moderately repeated (up to 1000 repeats in one locus) and highly repeated (more than 1000 repeats). They can be localized at one locus or at many loci of the same or different chromosomes. One and the same sequence can be repeated in different locations an unequal number of times. Mini- and microsatellite tandem nucleotide repeats are scattered throughout the genome and represent a combination unique to each organism in terms of the number of repeats at different loci and the number of loci. Their presence characterizes the genetic polymorphism of each individual, which is used for medico-genetic and forensic purposes, as well as in the passports of animal breeds. However, what specific functions are performed by these parts of the genome has not yet been precisely determined. Variants of the polymorphism in the coding part of DNA are also found in the exon and intron sequences of the molecule. These changes can be qualitative if they are caused by substitution or loss of nucleotides, or quantitative if the number of nucleotide repeats varies at a certain locus. The main type of genetic polymorphism is single nucleotide polymorphism. These are variants of DNA sequences with a change in only one base pair. Differences in one pair of nucleotides can occur in any part of DNA: exons, introns, intergenic intervals, or repeats. They are caused by mutations. A total of 1.42 million such differences have been identified in humans. People of the same sex are 99.9% identical in their nucleotide sequences, and only 0.1% of differences cause phenotypic variations in individuals. The significance of single nucleotide polymorphism is well illustrated by the example of the human genetic disease called sickle cell anemia. Its cause is a change in only one nucleotide in a triplet, which results in the synthesis of a polypeptide with only one other amino acid. Yet, the consequences of this are catastrophic: the formation of hemoglobin with a disturbed spatial structure, a change in its affinity for oxygen, a change in the shape of erythrocytes, and much more, which leads to a serious pathology. The sizes of human genes and the numbers of exons and introns in them vary over a very wide range. Most of human DNA genes have sizes from 1000 to 50,000 base pairs and the number of introns in them can be from 2 to 50. Many genes and gene families play an important role in early embryogenesis. The genes of human embryonic development are homologous to those in other mammalian species. Most of these genes regulate the production of proteins called transcription factors. They control RNA transcription by activating or suppressing

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gene expression. Key transcription factors control many genes that coordinate embryological processes, such as body segmentation, embryonic induction, migration, cell differentiation, and so on. Some DNA regions are capable of movement within the genome. Such regions are called transposons or “jumping” genes. They can move within a chromosome or “jump” into others, and they can be inserted into the middle of a gene, disrupting its work, or join at the end of a gene, changing its regulation. Some of the transposons act as enhancers (amplifiers), silencers (attenuators), or terminators (switches) of transcription. As a result of such movements, new genes can be created, and sometimes new characteristics of the organism can arise. Furthermore, mobile cellular elements can escape the control of the cell in the form of plasmids or viruses and transfer genes or groups of genes from one cell to another, or from one species of living organisms to another. A significant part of the human genome (up to 8%) is represented by proviruses, which are nucleotide sequences that are descendants of viruses. They could have appeared as a result of infection (about 50 million years ago) in the germ cells of some primates, and been inherited since then. Most of these ancient genes are “silent”, but under certain influences on the genome, they can be activated, and this can disrupt the life of cells by analogy with mutations. The complete set of genes and genome segments in cells and organisms forms a vast interconnected network with many feedback loops and many interactions. Moreover, practically all genes can directly or indirectly regulate each other’s activities or function together. However, despite significant advances in the study of the genome, the principles of organization and functioning of this mysterious system are still far from being fully understood. Genomes contain a variety of enzymes that are tools for manipulating DNA molecules and the information they contain (Table 14.1). A genome also contains a large amount of different structural and functional proteins, such as histones, non-histone proteins, the DnaA protein that recognizes the oriC site and directs all other enzymes, SSB proteins that prevent DNA renaturation, transcription factors, etc. Thus, the genome is a separate constantly functioning complex system. The main components of the genome are nucleic acids and hundreds of special proteins and enzymes. Taken separately, neither enzyme proteins nor nucleic acids exhibit any vital properties. Only their symbiosis in a colloidal environment generates a structural and functional system with a fundamentally new quality. Due to its autonomy, integrity, complexity, and self-sufficiency, the ability to reproduce and build a new phenotypic environment around itself, the genome must undoubtedly be considered the basis of the existence of living bodies, as well as the means for their creation and control.

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Table 14.1 Essential enzymes of a genome and their functions Essential enzymes of replication and transcription

Manipulations with matter

Manipulations with information

Helicase

Breaks hydrogen bonds between DNA strands

Splits the information carrier into two parts

Topoisomerase

Topoisomerases I and II cut single-stranded and double-stranded DNA, respectively

Cuts the information carrier into fragments

DNA polymerase α

Initiates replication in a complex with primase

Initiates duplication of information

DNA polymerase β

Repairs damaged DNA

Recovers lost information

DNA polymerase δ

Synthesizes the leading DNA strand

Duplicates information

DNA polymerase ε

Synthesis of lagging DNA strand and Okazaki fragments

Duplicates information

Primase

Synthesizes small fragments of Duplicates fragments of RNA primers and brings them information to the site of synthesis

Ligase

Connects Okazaki fragments, Consolidates fragments of i.e., forms 3' -5' phosphodiester information bonds

Gyrase

Twists DNA strands into a spiral

Completes the duplication of information

Telomerase

Completes the telomeric regions of chromosomes

Recovers information lost during division processes

RNA polymerase I

Synthesizes ribosomal RNAs (18S and 28S rRNA) in the nucleoli

Transfers information from DNA to RNA

RNA polymerase II

Synthesizes mRNA and some sRNA

Transfers information from DNA to RNA

RNA polymerase III

Synthesizes tRNA, sRNA, 5S rRNA

Transfers information from DNA to RNA

14.2 Stem Molecules of Life It is clear that nucleic acids constitute the material and informational basis of life. Or rather, life is based on the unique properties of nucleic acids to possess and implement information within the composition of genomes. The main molecule of life, DNA, is the custodian and supplier of genetic information. Through the use of DNA, living organisms and cells are able to multiply, grow, differentiate, and function. By analogy with stem cells, DNA macromolecules can be called stem molecules, since they provide the origin for all the other trillions of organic molecules from which the body is built, and thanks to which it functions. DNA forms the basis for

14.2 Stem Molecules of Life

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(a)

(b)

Fig. 14.1 Nucleic acids are the stem molecules of life. a. DNA molecules have the unique ability to reproduce indefinitely. This provides a stem of replication or reproduction—the horizontal stem of the flow of matter and information. b. DNA molecules are the predecessors of RNA and proteins, through which they generate all the necessary molecules in cells. They thus form the stem of expression or formation of living bodies—the vertical stem of the flow of matter and information

two directions of realization of genetic information, or one might say, two stem flows of matter and information (Fig. 14.1). Vertical stem. The vertical flow of DNA information (Fig. 14.1b) ensures the formation and development of living bodies. Genetic information is recorded in DNA molecules. It is realized in the process of individual development through transcription and translation, when an ordered, highly organized structure of living bodies is built according to the “genetic blueprints”. All three main types of RNA mediate the extraction and use of this information, which is realized through protein synthesis. Proteins constitute cells, organs, and bodies of various living organisms, as well as providing many of their properties and functions. This stem realizes and simultaneously transfers genetic information from the past to the present: from the information contained in the mother’s DNA to its actual incarnations in living bodies. Horizontal stem. The horizontal flow of DNA information (Fig. 14.1a) ensures the reproduction of living bodies. Genetic information is duplicated by DNA replication during reproduction, and then transmitted to daughter organisms as a result of mitosis or meiosis. In this case, the genetic information becomes hereditary. This stem of information realization is directed from the present to the future: from maternal DNA to the daughter DNA of the next generation.

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These two streams of matter and genetic information are decisive for the existence of living bodies and the planetary system of life. That is, these stem nucleic acid molecules are the materia prima of the phenomenon of life, the material and informational basis of the unity of all living things.

14.3 Genetic Material All representatives of the living world have programs of reproduction and development recorded in the genetic material of their genome. Genetic material is a set of complex dynamic macromolecular structures based on nucleic acids containing genetic information. In eukaryotes, it is found mainly in the nuclei of cells (Fig. 2.4). Less than 5% of nucleic acids are localized in mitochondria and chloroplasts.

14.3.1 Chromatin Most of the cells (99%) in the multicellular organism of an animal are in an active functioning state at the G1 phase of interphase (see Sect. 9.4, Fig. 9.3). The genetic material of the genome during this period of the cell cycle is present in the form of an organized system of nuclear chromatin. Individual chromatin fibrils constitute a complex of DNA molecules and proteins in an approximately 1:1 ratio by weight. The number of chromatin filaments is the number in the diploid set of chromosomes. Each filament is attached to the proteins of the nuclear envelope by the centromere and at both ends. Most of the chromatin is composed of fibers of very small diameter, which can be visualized under an electron microscope. Although the DNA molecules are very long, they are packed by histone proteins into a much shorter supercoil (Fig. 14.2). Histone proteins form nucleosomes around which a specific segment of DNA wraps. DNA strands stretch from nucleosome to nucleosome. Intertwining in an orderly manner within the nucleus, they form a chromatin network. That is, at the G1 phase of interphase, the genetic material of the genome is represented by an organized chromatin network. Depending on the degree of condensation, chromatin is subdivided into heterochromatin and euchromatin. Heterochromatin is highly compacted and genetically inactive. Differentiated cells usually have up to 90% of their chromatin in this form. Euchromatin is despiralized and much less condensed. Under an electron microscope it is observed as the lesser stained regions of the nucleus (Fig. 3.2). Euchromatin is genetically active. These regions of chromatin provide the information for the active formation of RNA.

14.3 Genetic Material

355

Fig. 14.2 Levels of organization of genetic material during interphase (1–3) and mitosis (4–6). 1— DNA strand; 2—nucleofilament; 3—30-nm fibre; 4—chromonema; 5—chromatid (in cross-section); 6—chromosome, consisting of two spiralized chromatids. Explanations in the text

14.3.2 Chromosomes Approximately 1% of the cells of a multicellular mammalian organism are in the stage of division (Chap. 9). On average, the duration of mitosis is several tens of hours. In this period of the cell cycle, autonomous chromosomes are formed from diffuse chromatin. A metaphase chromosome is an X-shaped structure containing in each of the two chromatids one densely packed daughter strand of a DNA molecule with associated proteins. Chromosomes in this conventional form exist only during the metaphase of mitosis (see Sect. 9.4) and are clearly visible under a light microscope. If a single DNA molecule, for example, of a human, is purified from proteins and stretched out, it will have a length of about 1.5 m. And after DNA replication, the number of strands in the 46 chromosomes doubles again! How can 92 long entangled threads be strictly ordered and placed in chromosomes in such a way as to be invisible to the naked eye? This is done by implementing chromatin supercoiling mechanisms and very efficient packing into the dense tiny bodies of microscopic chromosomes (Fig. 14.2). The levels of organization of the genetic and hereditary material of a genome are presented in Fig. 14.2. A DNA strand is a double polymer helix with a diameter of 2.2–2.4 nm, consisting of thousands of nucleotides (Sect. 1.5). It contains genetic information and forms the basis of the genome. A nucleofilament consists of nucleosomes formed by packing together a portion of a DNA strand and histone proteins. Histones are a group of proteins that perform two main functions: they are involved in the packaging of DNA strands and in epigenetic regulation of the processes of transcription, replication, and repair. The nucleofilament is very long and thin, consists of thousands of nucleosomes and linker regions, and has a diameter of 10–11 nm.

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14 Materials, Devices, and Mechanisms of the Genome

A 30-nm fibre is formed by folding a nucleosome strand into a tight helix. This level of spiralization is provided by a special protein, which, by combining with linker DNA and two neighboring nucleosomes, brings them closer to each other. Genetic material exists predominantly in this form during the interphase. After DNA replication in the S phase and the end of the G2 phase, cells are prepared for division and the formation of chromosomes, as a convenient form for manipulating genetic material, dividing it and transferring it to the daughter cells. The genetic material is compacted as much as possible, passing through several more levels of organization. A chromonema (300-nm fibre) is a coiled thread resulting from the folding of a 30-nm fibre into loops. Non-histone proteins, involved in their formation, are capable of recognizing specific nucleotide sequences of linker DNA and connecting them to each other. One loop of chromonema accounts for about 60,000 base pairs. A chromatid (700-nm fibre) is a tightly packed fibre formed by compacting chromonemal loops around the protein rod. A metaphase chromosome is the highest level of chromatin spiralization, which occurs exclusively during the period of cell division at the metaphase stage. It represents two chromatids connected by a centromere. The thickness of the arms of metaphase chromosomes can reach 1500 nm or more, so they become clearly visible under a light microscope. At this stage of the cell cycle, genetic information becomes inactive, conserved in the body of the chromosomes for the time they are being manipulated during genome division. At this point, genetic material and genetic information become hereditary and move passively to the daughter cells in the bodies of the chromosomes. During metaphase, all chromosomes are composed of two chromatids, consisting of maximally coiled chromatin. Each chromatid is a single double-stranded supercoiled DNA molecule bound to histones. Two daughter DNA molecules, which are located in two chromatids, are held together in the centromere region by an unreplicated DNA segment. A primary constriction divides chromosomes into the p-short and q-long arms (Fig. 14.2). The primary constriction (centromere) is the least spiralized part of the chromosome. A centromere is a common, non-replicated part of DNA. It contains special proteins that form kinetochores, to which spindle fibers are attached to divide the genetic material. This promotes separation of the daughter chromatids during anaphase. The site of the primary constriction in each pair of chromosomes is individual and constant, which generally determines its shape. The ends of the chromosome arms are called telomeres. They contain thousands of repeating sequences (TTAGGG). These are genetically inactive, specialized areas that prevent chromosomes from joining each other or with the fragments. A chromosome deprived of telomeres turns out to be “sticky” and easily connects to the same regions of other chromosomes. Thus, telomeres preserve the chromosome as an autonomous unit and ensure its individuality. Some chromosomes have secondary constrictions that separate sections of chromosomes called satellites. These regions of chromosomes contain rRNA genes. Such

14.3 Genetic Material

357

Fig. 14.3 Human karyotype diagram or karyogram. The karyogram is represented by a haploid set of metaphase autosomes and X and Y sex chromosomes. All the doubled hereditary genetic material of the entire genome is neatly packed into 23 chromosomes. They provide the perfect way for the transit of genetic material and hereditary information into the new bodies of subsequent generations

chromosomes can approach each other in the nuclei and associate, which contributes to the formation of nucleoli. The size of the chromosomes varies depending on the species of the organism. At the metaphase stage, they are generally 0.5–33 μm long and 0.2–2 μm thick. The chromosomes of different pairs of the same cell differ in size. The length of the chromosomes depends on the molecular weight of the DNA and proteins, as well as on the degree of chromatin coiling. The shape of a chromosome is determined by the position of the centromere on the chromatid. On this basis, the following forms of chromosomes are distinguished (Fig. 14.3): • metacentric—the centromere is located in the center of the chromatids and the arms of the chromosome are equal in length; • submetacentric—the centromere is slightly shifted relative to the center of the chromatid, the shoulders being somewhat unequal in length and divided into long (q-arms) and short (p-arms); • acrocentric—the centromere is located very close to one of the ends of the chromatid, and the arms differ significantly in length, with the small arms often having satellites, i.e., areas separated by a secondary constriction; • telocentric—the centromere is located at the end of the chromosome and the p-arms are absent. Such different sizes and shapes of chromosomes are due to the unequal sizes and features of the nucleotide structure of the packed DNA and the peculiarities of its

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packing. Yet, in all cases, each metaphase chromosome contains two daughter DNA molecules, packed in chromatids and connected by a centromere. Thus, the genetic material of the genome is represented by a discrete set of chromosomes at the division stage. That is, in dividing cells, chromosomes are formed from the active chromatin of the genome, which is necessary for the following cytogenetic processes: (a) for the multifold compaction of genetic material (in this case, the genetic material is “conserved” and loses its ability to express); (b) for the formation of structures convenient for manipulation during division (metaphase chromosome, consisting of 2 chromatids, kinetochora, and microtubules); (c) for the even distribution of genetic material between the daughter cells in the form of separate chromatids; (d) for decompaction of hereditary material, the formation of active chromatin, and the beginning of a new life for the genome.

14.3.3 Karyotype The karyotype is the genetic ID of a genome. Chromosomes can be stained and examined in the laboratory during the metaphase of a cell cycle. During this period, they always have standard sizes and shapes. The set of all chromosomes of a given cell, described in the metaphase stage of mitosis, taking into account their number, shape, structural details visible under a light microscope, and gene and allelic composition, is called a karyotype (Fig. 14.3). An essential characteristic of the karyotype is the number of chromosomes. This is a species-specific indicator (Table 14.2) which is the same in all healthy individuals of a given species. However, the number of chromosomes in the karyotype of an individual does not depend on the level of organization of the species and does not indicate phylogenetic relationship, since the same number of chromosomes can occur in species that are very distant from each other. The main differences in karyotypes are that each species of organism has a specific set of chromosomes of a certain shape and size. And most importantly, the chromosomes of organisms of different species have their own unique set of DNA, genes, and gene systems which determine the development of individuals only of a particular species. Therefore, the karyotype can be considered as the ID of a certain biological species. Or rather, the ID of a species of a genome (Chap. 18). Usually, an even number of chromosomes is found in the somatic cells of animals and plants. This is due to the fact that individuals who are born as a result of the sexual process receive 50% of their chromosome set from each of the parents. In this case, each of the parents transmits to the daughter organism one chromosome of each type (i.e., one chromosome responsible for a certain complex of characteristics). As a result, the daughter organism receives a pair of chromosomes responsible for the same traits. Chromosomes that are the same in properties, but received from different parents, are said to be homologous; they contain the same genes, but these genes are sometimes in different allelic states.

14.3 Genetic Material Table 14.2 Number of chromosomes in various species of living organisms

359 Common name of species

Binomial nomenclature

Number of chromosomes

Brewer’s yeast

Saccharomyces cerevisiae

32

Common wheat

Triticum aestivum

42

Roman snail

Helix pomatia

24

Fruit fly

Drosophila melanogaster

8

European carp

Cyprinus carpio

104

Chicken

Gallus gallus domesticus

78

Common rat

Rattus norvegicus

42

Dog

Canis familiaris

78

Common dolphin

Delphinidae Delphis

44

Chimpanzee

Pan troglodytes

48

Human

Homo sapiens

46

Non-homologous chromosomes have characteristics that are completely different from each other. That is, each pair of homologous chromosomes of an individual’s karyotype differs from other pairs in size, shape, and genetic composition. For example, the first pair of human chromosomes (metacentric, the largest) is very different from the 22nd pair (acrocentric, the smallest, with a secondary constriction and a satellite). They contain different genes that determine the development of different traits. A chromosome set containing two chromosomes of each homologous pair is said to be diploid. This set is characteristic of higher multicellular organisms capable of sexual reproduction. However, even in these organisms, only somatic cells have such a set, i.e., cells not associated with reproduction. Germ cells (gametes) contain only one chromosome of each pair, i.e., the total number of chromosomes in their genome is half that in the genome of a somatic cell. Therefore, when two such gametes merge during the sexual process, a new diploid cell is formed. The chromosomal set of germ cells is said to be haploid. The karyotypes of various organisms are rather conservative. Despite the sexual process, mutations, and recombinations of genetic material, only the allelic composition of DNA changes somewhat in genomes, while the chromosomal and genic composition remains stable. Therefore, there are no fundamental changes in phenotypes and phenomes for many millions of generations, which supports the existence of various species of living organisms for millions of years. Only significant chromosomal and genomic mutations of the genome have a substantial effect on the phenotypic framework of their owners. For the most part, such mutations are unfavorable, and their carriers do not survive or reproduce.

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On the other hand, the genetic material is highly plastic, subject to various influences and regulations, and exhibits controlled genetic activity. In different cells of a given organism, different combinations of genes of the same genome are expressed, resulting in the synthesis of different proteins and their ratios. This provides morphological and functional differences in hundreds of different cells of multicellular organisms. Therefore, along with strict conservatism, genomes have the highest plasticity, which ensures variability, differential expression, and a variety of phenotypes. In addition, the genetic material of the genome is also highly dynamic and demonstrates reversible changes in structure, shape, and function during the cell cycle (see Figs. 14.2 and 9.4, and Table 9.1). Thus, despite the fact that the genetic material of a genome is discrete, it is represented by an integral sum of various DNA molecules and a large number of diverse proteins. At the main stage of the G1 phase of the cell cycle, genetic material functions in the form of chromatin, whereas during mitosis it is conserved in the form of chromosomes. The biological significance and essence of the dynamics of transformations of chromosomes is the reproduction and uniform distribution of hereditary genetic material and information in the emerging cells. Chromosomes are a convenient device for preserving and dividing the hereditary genetic material of genomes into two parts, and then transferring them to daughter organisms. This is a perfect mechanism for the transfer of duplicated genetic matter and information to subsequent generations of carriers, and it is the ideal way to reproduce genomes and their phenotypic framework.

14.4 Genes Genes are discrete elements of genetic material and genetic information of genomes. They are the basic units of individual development, heredity, and evolution. They directly or indirectly determine the development of all traits of an organism. The transfer of genes over a number of generations through the process of reproduction ensures the transfer of the traits of parents to their daughter organisms. By analogy with the information units of computer programs, they can be considered as genetic files (Sect. 13.6, Table 13.1). According to the modern biological concept, genes are stable segments of DNA that perform specific intragenomic functions. For example, they encode RNA, enhance or weaken the action of other genes, participate in the movement of nucleotide sequences, etc. Genes consist of various functional segments, for example, a promoter, operator, exons, introns, etc. Each gene occupies a certain place (locus) in a particular chromosome. Besides, different genes have a different qualitative and quantitative nucleotide composition. Genes can exist in the form of several alleles that determine the variants of traits. Before cell division, all genes are duplicated during DNA replication, and then passed on to the offspring.

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361

When transcribed, structural genes are recoded into specific regions of RNA. Most major types of RNA are involved in the synthesis of proteins that ensure the structure and metabolism of cells and determine the development of traits according to the scheme: gene → RNA → protein → trait. Monogenic traits are defined by one gene. For example, human hair color is determined by the presence and intensity of expression of a gene encoding a protein pigment—melanin. Polygenic traits are determined by the manifestation of the activity of several genes. In particular, the size and shape of the body of an animal depends on many genes. There are also no separate genes for such complex traits as intelligence, obesity, and aging. There are no separate genes that determine membership of a biological race, species, or population. The set of genes of a given organism is called its genotype. Its differential expression in the process of development leads to the formation of a phenotype—the set of traits and characteristics of the body. Information in genes is encoded by a specific sequence of nucleotide triplets—the genetic code. The smallest genes consist of several dozen triplets, for example, tRNA genes. The genes of the large macromolecules rRNA and mRNA include several hundred and even several thousand nucleotides. Intensive studies of the functioning of structural genes have made it possible to distinguish many categories of their primary polypeptide products: enzymes, modulators of protein functions, receptors, transcription factors, proteins of the intracellular matrix and cytoskeleton, extracellular matrix proteins, transmembrane carriers, protein channels, cellular signaling molecules, hormones, contractile proteins, immunoglobulins, and many others. The largest group belongs to enzyme coding genes, which make up to 30% of the total number of structural genes. Gene activity is manifested by the presence of proteins in the cell or in the traits of organisms. Structural genes, of which there are thousands of varieties, are not directly involved in the synthesis of proteins, but constitute the templates for the formation of mediators, i.e., various RNA molecules that are directly involved in synthesis. Genes carry information about the structure of certain polypeptides. mRNA is transcribed from these regions of DNA, further directing the synthesis of proteins. Among structural genes, there are regulatory genes whose products regulate the functioning of other genes. The rRNA-encoding genes (several varieties) contain information about the structure of ribosomal RNA and determine their synthesis. The tRNA-encoding genes (more than 30 varieties) direct the formation of transport RNAs. A specific structural gene typically encodes the synthesis of a single polypeptide. This defines monogenic traits. Some genes can mediate the synthesis of several polypeptides through alternative splicing. A cell, an organ, or an organism can have many complex traits (polygenic), resulting from the interaction of many genes. The action of the gene is strictly specific, since the gene can encode only one amino acid sequence and regulates the synthesis of one specific polypeptide (except the alternative splicing). Some genes have pleiotropic action, determining the development of several traits at once. The activity of a gene can be influenced by factors of both the external and the internal environments. Genes are capable of recombinations and mutations, which

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14 Materials, Devices, and Mechanisms of the Genome

provide variability. However, DNA molecules are capable of repair; therefore, not all gene damage leads to mutations. Furthermore, transgenesis processes enable genes to be transferred, incorporated, preserved, and expressed in “foreign” genomes via the processes of transgenesis (Fig. 14.7). There are genes that are constantly expressed, because the proteins they encode are essential for constant cellular activity. In this way, a range of “housekeeping” proteins is synthesized, including ribosomal proteins, glycolysis enzymes, ion carriers, etc. These are constitutive genes that do not require special regulation. Non-constitutive genes are usually inactive, and expressed only when the protein they encode is needed by the cell. Such genes are specifically regulated by a cell or an organism. It should be emphasized that a genome, while being discrete (consisting of separate genes), functions as a whole. Genetic programs are recorded and stored as various gene sets. The results of the expression of genomes in a variety of traits are not individual genes, but their systems, known as genetic networks (Sect. 14.9). Genetic information networks cannot function independently, but require a genomic “executive system” in the form of a variety of special tools: enzymes, histone and non-histone proteins, structural polypeptides and their complexes, etc. This system manipulates DNA molecules and carries out transformations of genetic material and information, which ultimately leads to transformation of a certain material space into living bodies in accordance with genetic programs. Thus, the phenomenon of genome discreteness, i.e., the existence of genes and their networks, is what determines the plasticity of this system and the possibility of controlled manipulation of genetic information in any direction, which in turn determines the key biological processes: reproduction, development, heredity, variability, and evolution.

14.5 Genetic Code The uniqueness of the structures and functions of millions of different cells of all kinds of living organism is primarily determined by the specificity of their set of proteins. Cells are able to synthesize individual sets of proteins, as well as specific proteins through the use of a certain part of the genetic information recorded in the DNA molecules of their genome. This information exists in the form of a linear ordered sequence of nucleotides in the strands of nucleic acids and is called the genetic code. DNA structural genes are discrete units of genetic information that encode specific RNA molecules using nucleotide triplets. In mRNA molecules, a sequence of three nitrogenous bases such as AUG encodes a specific amino acid, namely, methionine. Therefore, the genetic code of mRNA is a certain strict sequence of nucleotides that determines the order of amino acids in a protein molecule (Fig. 14.4). Genetic code is used for compact coding of information and has the following fundamental characteristics: (a) Triplets. Three adjacent nitrogenous bases, called a triplet or codon, encode one amino acid. The codons are arranged one after the other without interruption. This means that the position of each amino acid in the

14.5 Genetic Code 1st base

U UUC UUA

C

A

C Phe/F

A

UCU UCC

UCU Ser/S

G Tyr/Y

UCC

UGU UGC

Cys/C

U C

UCA

UCA

Stop

UGA

Stop

A

UUG →

UCG

UCG

Stop

UGG

Trp/W

G

CUU

CCU

CCU

CUC

CCC

CUA

CCA

CUG

CCG

CCG

AUU

ACU

ACU

AUC

Leu/L

Ile/I

AUA AUG →

G

3rd base

2nd base

UUU U

363

ACC ACA

Met/M

GCU

GUC

GCC

GUA GUG →

Thr/T

ACG

GUU Val/V

Pro/P

CCC CCA

ACC ACA ACG

Ala/A

GCU GCC

GCA

GCA

GCG

GCG

His/H

Gln/Q

Asn/N

Lys/K

Asp/D

Glu/E

CGU CGC CGA

U Arg/R

A

CGG AGU AGC AGA AGG

G Ser/S

GGA GGG

U C

Arg/R

A G

GGU GGC

C

U Gly/G

C A G

Fig. 14.4 Genetic code of mRNA. This molecular language has been used and is still being used to record all the information programs making up the diversity of life. And many more programs will be recorded in this language to gradually replace aging organisms that are becoming incompatible with the evolving reality

polypeptide chain depends on the position of the triplet in the nucleic acid. (b) Specificity. Each individual triplet encodes just one specific amino acid. (c) Nonoverlap. One nitrogenous base in a certain triplet is never part of another triplet. (d) Punctuation marks. The genetic code does not have “punctuation marks” between coding triplets in structural genes, but it has many different signal sequences between other functional regions of the nucleic acid. For example, three variants of mRNA triplets (UAA, UAG, and UGA) do not encode amino acids, but are used as full stops in the information reading process. (e) Versatility. Numerous studies have confirmed the universality of the genetic code. That is, in all living organisms from viruses to plants and mammals, the same triplet encodes the same amino acid. This is one of the most convincing proofs of the unity and common origin of living nature. (f) Redundancy. Four nitrogenous bases, viz., adenine (A), thymine (T or Y), guanine (G), and cytosine (C) in combinations of 3 can form 64 different codons in nucleic acid molecules. Since there are 64 possible codon variants, and only 20 amino acids are actually used, the same amino acids can be encoded by different triplets (synonymous codons). That is, different triplets can have the same coding meaning. This advantage

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ensures the stability of living organisms: many spontaneous violations of the genetic “text” with a high degree of probability will not affect its meaning and will not cause dramatic consequences. (g) Collinearity. The amino acid sequence in a protein corresponds to the sequence of triplets in its mature mRNA. (h) Unidirectionality. The process of reading the information of the genetic code from the chain of the nucleic acid molecule goes only in one direction, namely, from the 5’ end to the 3’ end. (i) Compactness. A colossal amount of information is recorded in the DNA macromolecule with the help of small nucleotide molecules; sufficient, for example, for the development of a huge multicellular organism. (j) Molecular-digital principle of information recording. The matrix of the recording is the nucleic acid molecule, and the role of digital signs, by analogy with a computer, is played by the molecules of the nitrogenous bases. Biological informatics is a four-symbol system (A, G, T (Y), C). Thus, the coding of genetic information occurs on the basis of the genetic code (triplet → amino acid), by regular alternation of nucleotides, in a similar way to mathematical coding by alternating the symbols 0 and 1 in computer technology (see Sect. 13.6). Decoding of information is the process of decrypting and translating information into an acceptable form. DNA information is not directly available for understanding and use by a cell or an organism. At the first stage of decoding, this information is transferred to RNA molecules during transcription. In this form, the information can already be partially used by the cell with the help of special tools called ribosomes. When a specific gene is transcribed, the information encoded from the template DNA strand is rewritten to the complementary RNA molecule, where uracil is used in the RNA molecules instead of thymine. When structural genes are transcribed, the DNA genetic code is translated into the mRNA genetic code (Fig. 14.5). For example, if the sequence AAGCTATGCCAAA is located in the template DNA strand, then the mRNA molecule gets UUCGAUACGGUUU, that is, the same amino acids are encoded on the mRNA molecule by complementary triplets. In addition, mRNA has a start codon AUG, from which protein synthesis begins, as well as stop codons, which stop the process of polypeptide synthesis. At the next stage, direct translation of the information from mRNA molecules takes place using ribosomes. Here the encrypted information is read and specific proteins are synthesized (Fig. 14.5). The linear information of the mRNA nucleotide sequence is now transformed into the linear amino acid sequence of the polypeptides (translated into another language, i.e., recoded). After that, the shapeless two-dimensional linear structure and information of polypeptide filaments is transformed into the three-dimensional spatial structure and information of proteins (Fig. 14.5). Based on this information, proteins acquire the ability to interact with many biological molecules and perform special functions. Complete decoding and implementation of the initial DNA information into the real structures and functions of proteins occurs at the stage of modification. The joint functioning of the whole bulk of proteins is a prerequisite for the existence of biological bodies (see Sect. 1.6). The discovery of the genetic code and the system for encoding and decoding genetic information is one of the greatest human discoveries, but it has not yet

14.5 Genetic Code

365

Fig. 14.5 Gene expression in a cell. Explanation in the text

been fully understood. In particular, structural genes only contain information about the primary structure of proteins and the molecular mediators of their synthesis, RNA molecules. But it remains completely unknown how the information about the functions of proteins is recorded; how the information about body shapes is recorded; where the information about how biomembranes should be assembled from specific lipids and proteins is recorded; where the information about the shapes and sizes of cells is recorded; why certain cells are combined into tissues and organs of a strictly defined shape and size; what information determines the location of an organ or part of the body; where the information about biochemical processes and metabolic pathways, functions is recorded, and much more. These questions indicate that there are still unknown principles of coding, storage, and implementation of biological information. The enormous significance of the genetic code also lies in the fact that a single nucleotide nature, a single system for recording and using genetic information unites the entire living world and allows any interactions (communication) even at the level of genes and genomes. The communication of living organisms at the level of genetic information is carried out through the mechanisms of gene transfer within a single genetic information system of life (see Sect. 14.8) due to the universality of the language of all cells and organisms. Thus, the genetic code is a universal language of life, with the help of which a colossal amount of biological information is recorded, stored, and reproduced in countless genomes, on the basis of which genomes and phenomes are reproduced many times, their organization and ordering are maintained, and their properties and functions are ensured. That is, on the basis of the universality of the genetic code, there is a unified information system of life—the genosphere, the product of which is the unified organismic system of life—the phenosphere (see Sect. 2.6).

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14.6 Expression The set of cytogenetic processes and mechanisms for implementing information, which enables a gene to manifest its potential in a specific phenotypic trait, is called gene expression. This process is closely related to the decoding and use of information. The term “expression” is also used in a narrower sense to denote the transformation of the properties of proteins into a specific trait. All gene expression processes are energy-intensive and are supported by dozens of different enzymes. A gene is usually inactive, but when a specific protein is needed, a specific gene is activated, which causes the production of that protein. Thus, cells have a mechanism to control the amount of any protein at a specific time. Protein synthesis is also regulated by factors of the internal and external environment. During gene expression, the genome and the cell act together. Gene expression consists of several complex processes and steps (Fig. 14.5): (a) rRNA, tRNA, and pro-mRNA are synthesized on the basis of DNA genes. The first stage of expression takes place in the nucleus and is called transcription. In the process of transcription, not only the coding part of the gene is involved, but also other regulatory and structural parts. (b) The large pro-mRNA molecule undergoes processing, i.e., removal of nonfunctional areas. As a result, its size is significantly reduced and a certain spatial structure is formed, yielding a mature mRNA. At the same time, the tRNA matures and ribosome subunits are formed and transported to the cytoplasm. (c) mRNA with the participation of tRNA selects the necessary amino acids from the cytosol, and these bind into a strictly defined polypeptide sequence on the ribosome. The process of reading information from mRNA is called translation. It takes place in the cytoplasm. (d) Synthesized linear polypeptides undergo enzymatic modification and turn into functional proteins. The modification leads to another natural phenomenon— the emergence of a complex spatial organization of protein molecules. This is the basis for the specific interaction of molecules, which is the basis for the phenomena of life. (e) A protein contributes to the morphological or functional trait of a cell or an organism. This process is called expression. Thus, the implementation of genetic information occurs on the basis of information-material multistage processes, where the products of the previous stage launch the next one. Peculiarities of expression in prokaryotes. For prokaryotic cells, the concept of an operon as a regulated unit of expression has been developed experimentally and theoretically. An operon is a sequence of special, functional DNA segments that encode and regulate the synthesis of a specific group of enzymes from one metabolic chain, for example, glycolysis. The operon consists of the following structural parts: a regulator gene that controls the formation of a regulator protein; a promoter, a piece of DNA to which RNA polymerase is attached to begin the transcription; an operator, a site of a promoter that binds a regulator protein; structural genes, sections

14.6 Expression

367

of DNA that encode mRNA for specific proteins; a termination site, a segment of DNA containing a signal to stop transcription. Regulator genes are essential elements of the operon. They determine the synthesis of regulatory proteins under the influence of cellular factors. By connecting to certain nucleotide sequences of the DNA operator, such proteins can facilitate or prevent the attachment of RNA polymerase to the promoter. If a regulator protein prevents the enzyme from attaching to a promoter, it is called a repressor. In this case, the regulator gene carries out the negative control of transcription. If a regulator protein facilitates the attachment of RNA polymerase to the promoter and the initiation of the transcription process, it is called an activator, and the regulator gene carries out positive control. Peculiarities of expression in eukaryotes. The fundamental principles and the sequence of events leading to expression and its regulation are the same in both prokaryotes and eukaryotes. However, eukaryotes, especially multicellular organisms, are more complex. Indeed, the expression of their genes is much more complex and differs significantly in the details. In particular, we note the following features of expression in eukaryotes, as compared to prokaryotes: 1.

2.

3.

4.

5.

The genome of eukaryotes is significantly more complex. For example, the human haploid genome has approximately 25,000 structural genes located in 24 (22 autosomes + X and Y) chromosomes, whereas prokaryotes have only one chromosome and several hundred genes. In eukaryotic cells, the nuclear envelope separates the processes of transcription and translation spatially: chromosomes are in the nucleus, and ribosomes are in the cytoplasm. Gene expression in eukaryotes involves more steps. Therefore, they have a number of regulatory mechanisms that are absent in prokaryotic cells, such as processing. The expression of eukaryotic genes is influenced by gene amplification. This is a multiple increase in the number of copies of the same genes in order to intensify the synthesis of molecules required at a certain point in time. For example, repetitive DNA sequences include hundreds of copies of the rRNA and tRNA genes. Structural genes of eukaryotes contain introns, which are long sequences of nitrogenous bases that do not encode amino acids. Between the introns are the exons, which are the sequences that contain the codes for amino acids. RNA transcribed from a gene contains both introns and exons. It is called pro-mRNA. Its intron regions are removed by nucleases, and the informationcarrying regions, i.e., the exons, are merged together. The set of events in which pro-mRNA is manipulated and converted into mRNA is called processing. The process of controlled excision of introns and merging of exons is called splicing. Various regions of a gene can be cut differently and merged in different tissues and cells, which enables the formation of several variants of mature RNA. This mechanism is called alternative splicing. It allows the formation of several alternative polypeptide chains from the same gene.

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Operon organization of the genetic material has not been established in eukaryotes. Genes encoding the enzymes of a particular metabolic chain can be located on different chromosomes. They do not usually have a common regulatory system in the form of a gene regulator, operator, and promoter. Therefore, mRNAs synthesized in the nuclei of eukaryotes are monocistronic. The regulation of gene activity in eukaryotes is more complicated, since several regulatory genes are involved in this process at the same time. That is, the regulation of eukaryotic transcription is combinative. For example, eukaryotes have a special region on the DNA molecule near the promoter with approximately 100 pairs of special nucleotides. This is a binding site for a special protein called transcription factor, which ensures the successful attachment of RNA polymerase II to the promoter. 7. The genetic regulatory network is the genetic system in an organism that ensures the formation of phenotypic traits. Genetic networks are a collection (system) of genes of a genome that control the appearance and manifestation of a particular property or trait of a living body (see Sect. 14.9). Usually, the genetic network that controls a specific trait of an organism includes from several tens to hundreds of genes. A certain regulator of the network of genes encoding, for example, the enzymes of a certain metabolic pathway, activates the transcription of the entire cassette of these genes at once. The regulation of genetic networks is carried out according to the feedback principle. Any organism has a huge variety of gene networks that control the molecular, biochemical, physiological, and morphological traits. Each gene network has genetic mechanisms that ensure its regulation, based on changes in the functions of certain groups of genes that are part of the gene networks. 8. Another feature of eukaryotic genomes is the presence of special “amplifying” DNA segments, called enhancers, and “inhibitory” segments, called suppressors. They can be located at a great distance from structural genes. In turn, the enhancer and suppressor are regulated by various regulatory substances. Some regulatory proteins coordinate the activity of numerous genes, that is, they have a pleiotropic effect. 9. The genome of multicellular eukaryotes is subject to regulatory influences from the endocrine system of the body. Many hormones act as transcription inducers. Primarily, this applies to steroid hormones, which reversibly bind to receptor proteins that transfer them to the nucleus. This complex binds to a specific chromatin region responsible for gene regulation. For example, the action of testosterone activates genes that determine the development of the body according to a male pattern. 10. Another feature of the regulation of the activity of eukaryotic genes is associated with the formation of a DNA–protein complex, called chromatin. In this form, genes in nucleosomes are incapable of transcription. Therefore, a prerequisite for transcription is partial decompaction of chromatin and weakening of bonds with histone proteins. However, the nucleosomal organization of chromatin still remains partially during transcription processes.

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11. Control of gene expression in eukaryotes is also carried out at the translation stage, for example, by influencing the translation initiation factor. Therefore, the presence of mRNA in the cytoplasm does not always lead to actual protein synthesis. 12. The genome of eukaryotes is redundant. For example, only up to 5% of the 25,000 structural genes function in a human adult. In addition, the genomes of eukaryotes contain sequences that are repeated dozens, hundreds, and even thousands of times. Repetitive sequences perform a variety of biological roles: regulation of DNA reproduction, participation in crossing over, delineation of the border between exons and introns, etc. Certain repeated sequences may exhibit variable localization. They are called transposons or mobile elements. 13. Regulation of expression can also be carried out at the stage of post-translational changes. For example, formation of the active form of the protein hormone insulin requires the cutting of two chains from the proinsulin molecule, which are then crosslinked differently by disulfide bonds. 14. The process of ontogenesis of multicellular organisms involves differential gene expression. That is, different genes function at different stages of embryonic and post-embryonic development, ensuring the gradual, precise, step-by-step development of an organism. This provides selective differentiation of the cells and parts of a developing organism. During the life and functioning of an organism, the corresponding gene expression maintains the integrity of the body at a given period of the life cycle. Special groups of genes are expressed in various differentiated tissues and cells, thereby supporting the individuality of these parts of the body. Thus, the life cycle of an organism is a cycle of sequential differential expression of genes in a rather flexible genome. 15. Multicellular organisms have a system of stem cells. Differential expression of their genomes ensures the differentiation of cells, the formation of tissues and organs, and their development and maintenance of integrity. Prior to gene expression, the genome of these cells determines a certain path of development, leading to its structural and functional differentiation. 16. Fulminant embryonic expression of a genome. Embryonic development occurs on the basis of the fulminant expression of a zygote’s genome. Since it is known that ontogeny recapitulates phylogeny, and the developing embryo goes through all stages of morphogenesis, it is obvious that all the information for this is present in the genome. The accumulation of information took place in the genomes of ancestors for billions of years, and expression during embryogenesis occurs in just a few days or weeks. This is indeed a fulminant explosive process of material transformation in space, compressing a period of several billion years into several dozen days. In this way, as in a kaleidoscope, instantly, one after another, changes occur in the various forms and states of the phenotypic framework of a genome. The processes involved in the expression of genes and genomes are the most important mechanisms for recreating and maintaining the phenomenon of life. This

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provides the basis for the reproduction of cells and organisms, as well as their development and versatile functioning. It is the central link in the life process, connecting genetic information and living bodies into a single endless chain.

14.7 Template Processes. Copying and Cloning The multiple automatic copying of macromolecules, ordered structures, organized systems, and processes is characteristic only of living bodies. Copying is the process of reproducing identical versions of an original. The essence of the cloning process is a basic process of copying, but repeated many times. Copying and cloning are based on template processes, when many identical products are formed on the basis of one template in the process of expression; for example, as a result of replication, transcription, or translation (Fig. 14.5). Cloning enables the rapid replication and distribution of standard units of the system. The principle of “copying one’s own kind” underlies the preservation in time and space of the main evolutionary achievements, as well as rapidly and accurately repeated reproduction of typical structures, systems, processes, and functions that are of decisive importance for life. The copying and cloning processes are inherent in different levels of organization. In particular, DNA molecules are copied in the processes of replication, RNA molecules are copied in the processes of transcription, polypeptides are copied in the processes of translation, proteins are copied in the processes of post-translational modification, etc. Molecular complexes are copied as well. For example, standard membrane systems, ribosomes, spindle apparatus, and so on, are assembled in cells from generation to generation. Typical chromosomes, centrioles, cytoskeletons, actomyosin complexes, etc., are formed. Organelles are also copied, since, during cell division, not only genetic material, but also a certain part of the ordered internal content, including organelles, highly organized cytosol, ribosomes, etc., gets into each of the daughter cells. Genomes are copied during mitosis or meiosis (Chap. 9). The zygotic genome is maternal for all cells of a multicellular organism. Cells are copied in the process of division. Due to the differential expression of a standard genome, clones of cells of various structures and functions are produced in multicellular organisms. Their complexes form different organs and tissues. Cellular processes and mechanisms are copied and replicated by copying structures and systems. For example, after cell division, we observe completely ordered compartments. They already contain all the necessary enzymes and other conditions for the flow of strictly defined biochemical processes. One of the most important aspects of continuous reproduction is the copying of information. This occurs on the basis of the major cytogenetic processes of replication, transcription, and translation. As a result, organisms are copied. Most of the copying and cloning processes in biological systems are templatebased. Basic parent structures serve as templates for the formation of thousands of

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identical elements. This enables very rapid synthesis and replication of hundreds and thousands of required molecules. Copying and production of proteins is the main mechanism for the implementation of genetic programs in specific bodies and processes. The production process goes to the desired level of cell saturation with this or that protein. Template processes make it possible to extract genetic information with amazing accuracy, very quickly, and very economically, enabling the realization of many copies of the molecules necessary for cells and organisms. Importantly, copying and cloning of information occurs simultaneously with the copying of structures and processes. Furthermore, this information is both genetic, in the form of nucleic acids, and phenotypic, in the form of structures and processes. Thus, descendant living bodies, carrying the same potential as their ancestors, arise by copying and cloning genotypic and phenotypic information. The increase in entropy and resulting variability are spontaneous and inevitable. In order to be stable and not disappear, living organisms must constantly struggle with an increase in entropy, and this is possible only for a certain period time. Therefore, for a reliable long-term existence, it is necessary from time to time to reproduce exact copies of oneself . Copying and cloning is the basis for preserving and spreading the organization of matter and information inherent only in living bodies. And the genome, which pursues its own selfish goals, is a direct participant and manager of all these events.

14.8 Functional Systems of Genes It has now been established that the units of genome expression in various traits are not individual genes, but their systems—genetic networks. This can be exemplified by a system of genes encoding enzymes of a particular metabolic pathway. In this case, the key regulator of this system immediately activates the transcription of an extensive cassette of these genes, which completely provide all biochemical reactions with enzymes and regulators. As a rule, the gene network that controls a certain trait of an organism can include from several tens to hundreds of genes. A huge number of such genetic systems can function in a genome. Consider, for example, a gene network that mediates differentiation and maturation of erythrocytes, which is triggered by erythropoietin. By binding to the erythroblast cell receptor, it activates the protein kinase signaling pathway into the cell nucleus. As a result, transcription factors move into the nucleus, activating the transcription of a number of genes, including the gene encoding the GATA-1 factor. This is key in the erythropoiesis network. Its binding sites are found in the regulatory regions of all the relevant genes, including the promoter of the GATA-1 gene itself. This ensures the activation of GATA-1 gene transcription by a positive feedback mechanism after it is triggered by a primary stimulus. The promoter of the gene encoding the erythropoietin receptor also contains a binding site for the GATA-1 factor, which activates its transcription. As a central regulator of the gene network,

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GATA-1 ensures the simultaneous activation of a large group of genes required for erythrocyte differentiation and maturation. This case demonstrates the significant role of positive feedbacks, which ensure the effective guidance of the controlled parameter in the desired direction. They play a key role in gene networks for cell growth and differentiation, organ morphogenesis, and growth and development of organisms, in which the system is continuously in a state of development. The genome of any organism has an immense variety of gene networks and systems that control molecular, biochemical, physiological, and morphological traits. Each gene network has genetic mechanisms that ensure its regulation, based on a change in the functions of certain groups of constituent genes. In eukaryotes, the regulatory regions of genetic networks of DNA are huge; they can be an order of magnitude larger than the size of the coding parts of structural genes. These areas can contain dozens of regulatory elements. For example, the regulatory region of the rat tyrosine aminotransferase gene contains 40 regulatory units—binding sites for various transcription factors. The length of this region is approximately 10,000 nucleotide pairs, which is 10 times the size of the coding part of the gene. Thus, the genomes of eukaryotes have tremendous opportunities for regulation. The same gene in a multicellular organism can function in different gene systems of different cells, tissues, and organs. Depending on the conditions, in response to various influences of the external or internal environment, a very specific set of regulatory transcription factors is formed in the nucleus of a particular cell. By binding to special sites within the regulatory region of a gene, they provide specific expression of this gene in the general cytogenetic response system. As a rule, the gene networks of a genome are organized in such a way that each of them has one central regulator, viz., a transcription factor that simultaneously activates a large group (network) of genes. Systemic activation of large groups of genes is of great functional importance, because they encode a similarly large group of proteins that must be present in the cell simultaneously and in stoichiometric amounts in order to perform certain molecular genetic or metabolic processes. For example, during erythrocyte differentiation, the GATA-1 factor activates the system of genes encoding all enzymes that provide heme synthesis, as well as alpha and beta subunits, that is, the entire set of molecular components necessary for the formation of hemoglobin molecules. If a mutation occurs in the region of the central regulator, this leads to a simultaneous change in the work of the entire complex of controlled genes, and as a consequence, a change in the set of determined phenotypic traits. It is these mutations that have great evolutionary potential. Most likely, they were the basis for the emergence of new morphological and physiological systems. There are also so-called gene integrator networks. These gene networks play an important role in the integration and coordination of the function of local gene networks responsible for the performance of certain target functions. Such networks, through the reception system, receive an external activating stimulus, transform it into various specific forms, and distribute signals through their outputs connected with other gene networks, ensuring their activation. In turn, each of these gene networks

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transmits the received signals to other associated gene networks. That is, gene integrator networks are the key elements of the genome that ensure the distribution of stimulus over the entire organism. Any genetic network includes an executing component that ensures the implementation of the basic process, and a regulatory component that provides tuning of the ongoing processes to the required level of intensity, depending on the internal state of the organism and the parameters of the external environment. Consider, for example, the tricarboxylic acid cycle. The executive component includes the provision of 139 separate metabolic reactions. However, the regulatory component provides a much larger number of regulatory processes, in fact, 1882 of them. That is, one metabolic process accounts for an average of thirteen regulatory processes. This means that the complexity of the regulatory component of genetic networks is an order of magnitude higher than the executive one. Having formed billions of years ago, the executive components of genetic systems of basic metabolic processes are fundamentally similar in representatives of various global taxa, from archaeobacteria to eubacteria and eukaryotes. However, the regulatory components of the processes of basic metabolism differ significantly even between closer taxonomic levels. This means that during the 3 billion years of evolution of life on Earth, the targets of evolutionary transformation were primarily the regulatory systems of organisms. In turn, this may indicate that the evolutionary process is not spontaneous, but may be caused by directed modifications of the regulatory components of the genome. Regarding the executive component in metabolic systems, it has remained practically unchanged during the long period of evolution. In particular, the number of genes in most of the known eu- and archeobacteria is approximately the same, i.e., 2500–4500 genes (2.2–4.6 million base pairs). Apparently, this is the minimum required to ensure survival and reproduction. This number of genes is approximately the same in the simplest eukaryotic organisms. For example, in unicellular yeast, the genome involve 12 million base pairs, which corresponds to about 6–7 thousand genes, which is close to the value for bacterial cells. Thus, in the simplest eukaryotic organisms, despite the presence of a nucleus, diploidy, a complex system of biomembranes, cytoskeleton, etc., there was no quantitative or qualitative increase in the complexity of the genome, as compared to prokaryotes, judging by the number of genes. Most likely, significant phenotypic differences were due to mutations precisely at the level of the regulatory component of genomes. That is, it can be assumed that no fundamental changes occur in the genes of the executive system; it is only those of the various regulatory genetic networks of the global genome that vary to regulate the expression of different traits of the global phenome, necessary at a certain time and under certain conditions. This hypothesis explains very well the phenomenon of drastic and simultaneous “evolutionary leaps”. A qualitative leap in the complexity of the organization of molecular genetic systems (assessed by the number of genes) occurred with the emergence of multicellular organisms. This was associated with the appearance of new genetic networks and the components used to regulate them.

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For example, one of the simplest multicellular organisms, containing about 1000 cells, the nematode worm Caenorhabditis elegans, already has about 19 thousand structural genes, which in order of magnitude is quite close to the number of genes in humans with 25 thousand genes. Drosophila has about 12 thousand genes and angiosperms have 15–25 thousand genes. Likewise in fish, amphibians, reptiles, and mammals, there is one order of magnitude in the number of genes in the genomes. However, the phenotypic characteristics of the listed organisms differ significantly. This indicates that in multicellular organisms there is no direct relationship between the number of genes and the phenotypic complexity of the organism. Such colossal differences are most likely associated with the variability of the regulatory systems and genetic networks of the genomes of the various organisms. Genetic functional systems are highly dynamic. That is, some genes can function as part of different genetic networks, as exemplified by genes for various transport and ribosomal RNAs. Depending on the regulatory signals, various groups of genes can be involved in the systems. Thus, far more traits can be expressed than would be suggested by the number of genes available. That is, both the quantity and quality of traits are determined, apparently, not only and not so much by individual genes as by their various combinations and unions in genetic networks. If we proceed from the fact that there are about 25 thousand structural genes in the human genome, then their possible combinations in genetic networks is virtually unlimited. This in turn provides for a virtually unlimited variability of macro- and micro-traits and their combinations in Homo sapiens. The remarks above also imply that there are no specific genes for complex traits. For example, there are no genes such as a gene for aging, a gene for intelligence or talent, a gene for obesity, a gene for a specific function, property, or ability. There are also no specific genes that determine an individuum’s membership of a certain species—no human gene, no chimpanzee gene, no cat or mouse gene. All these complex sets of traits are determined by functional gene systems that are specific in each case—genetic networks that include tens, hundreds, and thousands of genes. Some traits are the same for different species and even types and kingdoms of living organisms. For example, the process of glycolysis is typical for almost all living organisms. This suggests that the same genetic networks can function in diverse, very different organisms, despite their having completely different genomes. Furthermore, the variety of species of living organisms is determined not only and not so much by the qualitative and quantitative composition of genes, but by various options for combining them into functional systems. The global genome is one, and many living bodies are just variants of the expression of its systems, just as one kind of genome is expressed in different ways in the diverse cells of a multicellular organism. The process of ontogenesis in a mammalian organism, based on the constant differentiation of a genome (Sect. 10.4) and switching of genetic networks, initially involves the formation of cells of the blastula, gastrula, ectoderm, mesoderm, and endoderm from a zygote, followed by the formation of hundreds of varieties of cells, then tissues and organs. An amazing diversity of cells emerges, including neurons, hepatocytes, fibroblasts, leukocytes, adipocytes, myocytes, and many others. At the same time, not only the phenotype of the cells, but also the structural and functional

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organization of the genome itself change greatly. This can be judged by the modifications of the nuclei of differentiated cells, which is clearly visible even under a light microscope (Fig. 10.2). Changes occur in the shape and size of the nucleus, the ratio of eu- and heterochromatin, the size and localization of nucleolar zones, etc. This indicates extremely complex molecular-genetic rearrangements of a genome in the process of ontogenesis. That is, the differentiation of cells, and also the maintenance of a differentiated state, are associated with the specific selective expression of genetic networks of a differently differentiated genome in different parts of the body. Hence, genes do not function alone, but are expressed as whole groups, united by the genome into functional systems. The aggregate of the genomes of individuals of the same species can also be considered as a specific genetic network system (Sect. 2.6). Moreover, this network is an integral part of the overall genetic network, namely, the global genome system. In turn, based on the expression of the global genome, the system of the global phenome is formed and maintained, and this includes the entire set of individuals and their genetic networks.

14.9 Directed Genome Rearrangements The synthetic theory of evolution views the genome as a passive structure that encodes and transmits randomly occurring DNA mutations and recombinations. It believes that only natural and artificial selection play an active role, selecting and fixing useful genome modifications into adequate adaptive traits. That is, the genome can react to the information it receives from the external environment, but only following the conditions created by artificial or natural selection. According to the theory, it cannot condition the directed creation of such adaptive programs by itself. However, in recent years, it has become increasingly obvious that the genome is, above all, a self-regulating and self-organizing system. This information-genetic system includes not only material for the development and evolution of living nature, but also the molecular mechanisms of its own directed modification to create new genetic programs, active participation in the process of its own evolution, and the evolution of its derived phenotypes. A view has recently emerged that the most successful genome is the one which, if necessary, is able to significantly and quickly change in a certain direction. That is, the genome contains mechanisms that generate and regulate coordinated DNA rearrangements. It is likely that these molecular mechanisms are triggered by a cell (phenotypic framework of the genome) that has direct contact with the external environment. The mechanisms of an adequate response of the genome to environmental factors could arise in the same way as any other function, and then evolve together with its carrier. Eventually, such a function becomes characteristic also of the genomes of multicellular organisms. This is consistent with our concept of the primacy of the genome, which builds a phenotypic framework around itself in the

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form of a cell or a specific body, mediating interactions with the external environment (Fig. 2.4). It has been noticed that the activation of genome rearrangements is often observed at the very moment when the organism needs it. This means, first of all, the presence of cellular mechanisms for transmitting information from the external environment to the genome and the presence of the molecular mechanisms for an adequate response. Metamorphosis processes (Chap. 17) are good examples of purposeful self-reprogramming and modification of genetic networks. The executive mechanisms that could participate in targeted genome rearrangements are, for example, mobile genetic elements. It is known that transposons play a significant role in natural genetic engineering. They are considered as intragenomic molecular systems that induce DNA rearrangements which underlie a variety of genotypic and phenotypic changes. The sizes of transposons range from several hundred to several thousand base pairs. In a chromosome, they can be present in several copies. From time to time, transposons can be activated by their own enzyme and transferred to some other DNA region within the same genome. This process is called transposition. The reaction is catalyzed by enzymes called transposases. Mobile genetic elements combine the ability to move, capture, and transfer adjacent nucleotide sequences, create retrocopies of transcribed sequences, and ectopically recombine homologous sequences. These traveling DNA regions are involved in the creation of new regulatory elements within their own genome. Furthermore, the study of genome rearrangements shows not only that the very moment of activation of the mechanisms of variability is not random, but also that the spatial distribution of changes is also far from random. Although it is still not clear what triggers transpositions. In recent years, a new branch of genetics and molecular biology called genomics, which studies the molecular organization and mechanisms of functioning of genomes, has been developing very intensively. Comparative genomics is expected to clarify our understanding of the forces and patterns that underlie the formation and development of genomes. The existence of “cold” and “hot” regions of genome variability, specialized “fragile” DNA regions, evolutionary breaks and rearrangements of chromosomes, mechanisms of the emergence and spread of segmental duplications, uneven genomic variability in different species—all these things will significantly add to our ideas about the evolution of the genome postulated by the synthetic theory of evolution. Deciphering the primary sequences of the genomes of various organisms and making comparative studies of them will provide a huge amount of material, and its analysis may well reveal the mechanisms of directed evolution of the genome which probably determine its relatively rapid rearrangements. In addition to programmed genome rearrangements, there are apparently also intracellular molecular systems that determine the locus-specificity of the appearance of mutations in DNA. There is probably a piece of molecular apparatus for attracting activated protein complexes to certain loci and at a certain time. This means that there is a special piece of cellular molecular apparatus that connects the information of the external environment directly with the genome. This mediator

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determines both the temporal and spatial coordinates of the functioning of the mechanisms that purposefully reconstruct the genome. Clearly, both the functioning and the rearrangements of the genome are determined not only by the elements of nucleic acids, but also by dozens of different proteins and their complexes. That is, the role of the protein component of the system of genome functioning and rearrangements is no less important than its nucleic component. Several mechanisms can be distinguished that control both programmed and nonprogrammed rearrangements of the genome. These are, for example, DNA elements for specific binding of regulatory proteins, complementary interactions between RNA and DNA, as well as epigenetic modifications of histones (e.g., structural changes) and DNA (e.g., methylation). In addition, mechanisms regulating DNA metabolism, in particular, enzymatic molecular complexes carrying out replication, transcription, repair, DNA modifications, condensation and decondensation of chromatin, and a number of others, can also participate in the processes of genome rearrangement. These mechanisms were discovered during the study of genomic variability in tumor cells, transposition bursts, spontaneous mutagenesis of yeast, etc. Thus, it is likely that a variety of stress conditions favor the switching of mechanisms of regulation of DNA metabolism to work on directed rearrangement and reconstruction of the genome. There is also a type of epigenetic inheritance that is not associated with the genetic code of DNA. This is exemplified by a modification of histones or a change in the conformation of nucleic acids. They can slowly accumulate, consolidate, and strengthen as a result of inheritance. After that, such modifications at some point, under the influence of internal or external factors, activate the mechanisms of variability and can play an essential role in the directed reconstruction of the genome, creating regions of genomic lability and conditions for rearrangements of the genetic material. Phenomenon of parthenogenesis is an excellent confirmation of the primacy of the genome and its ability to directed self-organization and implementation. Complete natural parthenogenesis is quite common in many invertebrates. It is also characteristic of a number of vertebrates: some species of fish, amphibians, and reptiles. This phenomenon may indicate an autonomous motivation of the genome for reproduction and survival. Even with the availability of an individual of the opposite sex, the haploid genome of an egg can independently decide to reproduce without the mandatory fertilization. Consequently, the genome is a dynamic and rather plastic system, which constantly undergoes modifications. Importantly, many changes occur in a directional and natural way, and not as a result of blind chance. Clearly, for a cell that has a unique molecular instrument for using and rearranging the genome, it makes sense to use it exactly at the moment when rearrangements are necessary for survival and evolution. From this point of view, mobile genetic elements (including viruses) are not parasitic DNA, but tools of natural genetic engineering. Numerous enzymes of mobile genetic elements, such as integrases, reverse transcriptases, endonucleases, transponases, etc., can modify the genome by means of insertions, duplications, inversions, and transductions. Thus, mobile

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Fig. 14.6 Induced programmed rearrangements of a genome and its phenotypic framework. By creating special conditions “in vitro”, it is possible to change the expression of a genome in a directed manner and transform differentiated cells into induced pluripotent stem cells. Such cells have a virtually unlimited proliferative potential and the ability to differentiate into any cell type. Reprogramming of the genome is accompanied by significant rearrangements of the genetic material. Moreover, the genome differentiates first, and only then does the differentiation of its phenotypic framework take place. The plasticity of the genome, which changes its framework depending on the experimenter’s commands, is amazing

genetic elements reconstruct the genome, contributing to the emergence of targeted mutations through recombination. Mobile elements of the genome may be inactive for a number of generations. However, genomic stress caused by external impacts, or arising, for example, due to recombination errors, immediately, or after several generations, induces transpositional changes in the genome, phenotypically directed against the harmful factors. Genomes of differentiated cells are capable of reprogramming, changing the quality of expression and converting cells first into stem cells and then into other differentiated cells (Fig. 14.6). Therefore, modern studies indicate that, along with the classical concepts of the mechanisms and active forces of evolution, it is extremely important to consider the possibility of purposeful modifications of the genome. The processes of both adaptation and evolution are not random, but rather purposeful. Obviously, the genome turns out to be not only a structure that encodes and transmits randomly occurring mutations for active selection, but also a self-organizing and self-regulating system. It contains both information for development and evolution, as well as molecular and cellular mechanisms for its own directed modification and changes in its phenome. The master genome paves the way for its existence under various environmental conditions, using its phenotypic framework as a means for interacting with the world.

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14.10 Transgenesis Within biological species, genes are transferred “vertically”, from parent to offspring during reproduction, or from DNA to RNA during transcription, as detailed in Chap. 9 and Sect. 14.2. The transfer and insertion of genes of one biological species into different parts of the genome of other species is carried out by “horizontal” gene transfer. This phenomenon has virtually no limitations, since the genomes of absolutely all organisms have the same nucleoprotein nature and the unified genetic code. Genetic engineers, using special methods for manipulating molecules, have convincingly demonstrated the possibility of horizontal transfer of foreign or modified genes in the laboratory, calling this process transgenesis. We use the term transgenesis in a broader sense, thereby denoting the entire set of all types of relocations of all kinds of genes within the global genome of the planetary system of life (Fig. 14.7). Transgenesis occurs all the time in nature. Transformation, transduction, and conjugation are the most ancient mechanisms of transgenesis and information transfer in prokaryotes. A simple example of transgenesis is the infection of an organism with a virus. This process can be considered as genetic aggression of viruses against the cells of a particular organism. Viral nucleic acids penetrate into cells, where, using special enzymes and host processes, they integrate into foreign host DNA and produce numerous bodies of their own kind. The transgenic region can be expressed simultaneously with the genes of the host cell, which ensures the multiplication of viruses, or it can exist for a very long time in a latent form as a provirus. Another example of natural transgenesis is the ability of the soil bacterium Agrobacterium tumefaciens to induce tumors in plants, which is associated with the transfer of the T-plasmid into the genome of plant cells. This is nothing more

Fig. 14.7 Certain possible pathways of transgenesis. Any directions of both vertical and horizontal transfer of genes and genetic information are possible in the single information space of the global genome

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than the transfer of genes between representatives of different kingdoms of living organisms. Scientific publications report the possibility of transferring genetic material between the cells of individual mammalian organisms, which is confirmed by the expression of marker genes in recipient cells. The ability of DNA segments to penetrate even through the barriers of the digestive tract is evidenced by scientific work on the detection of marker regions of nucleic acids of genetically modified food in the tissues of the studied animals. Over the past few decades, scientists have learned to artificially create conditions for the transfer of genes from one organism to another. For this purpose, a set of genetic engineering methods has been developed. They include the synthesis of certain genes, cutting of specific genes from DNA, identification of genes, production of plasmids (vectors), insertion of genes into plasmids, transfer of genes into a foreign genome, etc. Methods of genetic engineering can already enable genetic therapy of some hereditary human diseases, molecular diagnostics of diseases, and the production of transgenic organisms. Transgenic organisms are creatures that contain foreign genes in their genomes, intentionally inserted by a human using the methods of molecular biology. At present, many such organisms have been created. In particular, transgenic mice, rams, fish, monkeys, and other organisms already exist. They contain foreign genes in their genomes, determining the presence of new traits. Transgenesis appears to have been common in primordial life forms billions of years ago. This was as powerful a factor in evolution as mutation, as it led to the enlargement and diversity of genomes, which in its turn led to the emergence of new phenomes. Natural selection fixed the best adapted organisms, which gradually led to the emergence of new biological species. The transfer of genetic information still plays an important role in the evolution of prokaryotes, which have special mechanisms for this: transformation, transduction, conjugation, transfer of plasmids, etc. Viruses and mobile genetic elements carry out transgenomic transfer of genes within the single system of the global genome of the unified planetary system of life. Apparently, at a certain stage of evolution, cells began to “produce” viruses and other derivatives of their genomes. Plasmids, viroids, viruses, and then episomes, ISelements, and transposons became a means of exchanging genetic information within the planetary system of life. Based on a single polynucleotide nature, these mobile genetic elements began to participate in the processes of variation and evolution. That is, viruses and their analogues were formed as a global molecular mechanism for the transfer and exchange of genetic information between the genomes of various cells (viruses, viroids, phages, plasmids), as well as within individual genomes (transposons, IS-elements). They combined the processes of horizontal (from one species of genome to another, from one species of organism to another) and vertical (replication, transcription, translation, expression) transfer of genetic information into a single bioinformation circulation network within the common genome of life. It can be assumed that mobile genetic elements constitute the mechanism connecting all discrete genomes on Earth into a single information field, i.e., into a single global genome or genosphere (Fig. 14.7). Then any mutations and recombinations of the

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genome of any organism become the property of the entire system and can manifest themselves in numerous unpredictable phenotypic forms. Furthermore, any gene or segment of a nucleic acid can be transferred to any part (in any species of genome) of a single information field. Thus, all living matter is united by the streams of bioinformation circulating within the planetary system of life (see Sect. 8.4.7). The presence of a single information space and the global interconnection of all carriers of information determines the integral perception of any genetic fluctuations caused by the transmission of mobile genetic elements to any part of a single network of life and their manifestation in all kinds of inconceivable forms. Such fluctuations of genetic information may be among the most important mechanisms of evolution. That is, the evolution of living bodies, which is manifested by qualitative and quantitative changes in the composition of the global phenome, is a secondary phenomenon. Whereas the primary processes of evolution, causing changes in the system of phenomes, are molecular processes of genome modification caused by mutations, recombinations, hybridization, and also transgenesis. Horizontal (from the genome of one biological species to another) and vertical (within one species of genome) gene exchange support the genetic integration of all species of living organisms into a single system. Due to billions of years of horizontal gene transfer, prokaryotes have virtually no “pure species”. In eukaryotic organisms, as a result of isolation and different mechanisms of adaptation and survival, genetically and phenotypically separate groups of organisms began to appear, comprising relatively endogamous classes and species. However, despite the phenotypic differences, the entire prokaryotic and eukaryotic biomass of the Earth is nothing more than a single living organism, which is a derivative of its single complex global genome. Moreover, the species of genomes and species of phenomes are interconnected into a single system not only through the circulation of genetic information, but also through the interdependent genetically determined behavior of living bodies. Thus, genes can be transferred, incorporated, exist, and be expressed in “foreign” genomes. This is enabled by the common physical and informational nature of genes and genomes. Transgenesis is a grand, life-defining phenomenon! It demonstrates the enormous potential of the phenomenon of life for very fast (on the time scale of the Universe) and very significant modifications of taxa. The transfer of genes between genomes in a single information space of living bodies, along with DNA mutations and recombinations, could be the main reason for revolutionary leaps in the development of living nature.

14.11 Summary The genome is not only a collection of genetic information of nucleic acids, but also an essential structural and functional complex. This is a distinct part of the cell containing a complex of nucleic acids, various proteins, and structures, organized into a single system. This complex system contains genetic material and information, but also tools and mechanisms for their implementation. The genome is the dominant

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part of the diverse phenomenon of life. Its power and authority extend to individual cells, individual organisms, biological species, and the planetary system of life as a whole. DNA is a stem molecule and has the unique ability to reproduce itself indefinitely. On this basis, the stem of replication or reproduction is formed. They are also the predecessors of RNA and proteins, whereby they determine the appearance of all other necessary molecules in cells. They form the stem for the expression or the formation of living bodies. The phenomenon of genes determines the most important processes of fixation and operating with genetic information, which determines the key biological processes of reproduction, development, heredity, variation, and evolution. Genes do not usually function alone, but are expressed in whole groups, united into functional systems (networks). Such a network, which controls a certain trait of an organism, contains from several tens to hundreds of genes, and a great variety of such genetic systems is at work in every genome. Having a single physical and informational nature, genes can be transferred, incorporated, exist, and be expressed in “foreign” genomes. Genes realize their information in the form of a trait through expression—a sequence of complex molecular genetic processes—an intricate system for extracting and using information. Copying and replication of nucleic acids and proteins are the main mechanisms for the implementation of genetic programs into specific bodies and processes. This is the basis for preserving and spreading the principles of organization of living matter and biological information, which are characteristic of living bodies. Information on all possible manifestations of life is stored and used in the form of a universal genetic code. It is a universal language of life, with which a colossal amount of biological information is recorded, stored, and reproduced in countless genomes, on the basis of which living bodies are repeatedly reproduced, their organization and orderliness is maintained, and their properties and functions are ensured. That is, built upon genetic material, information, and code, there is a unified information system (the genosphere) comprising the totality of all living bodies on Earth (the phenosphere). Recording, storage, and expression of information can be carried out using the code, and all living beings can engage in molecular genetic communication with each other through horizontal and vertical gene transfer. Molecular elements and systems of the genome are capable of self-directed modification in response to changing environmental factors, generating useful traits for adapting their phenotypic framework to actual conditions. The genome is a structure that encodes and transmits randomly occurring mutations for active selection, but it is also a self-organizing and self-regulating system.

Part IX

The Dual Nature of the Phenomenon of Life

Chapter 15

Living Bodies and the Planetary System

15.1 The Duality of Life Life is represented by individual living bodies (cells and multicellular organisms), which are the possessors of individual life, as well as by the planetary system, consisting of trillions of representatives of different biological species. Together they constitute the global phenomenon of life (Fig. 2.6). That is, life has a dual nature: on the one hand, there are the individual living bodies, and on the other hand, there is the planetary system comprising all these living bodies. The characteristics and properties of these two components of the phenomenon of life differ in many respects (Chap. 2, Table 2.1). Life as a phenomenon appeared on Earth in the form of a stable system of prokaryotes (see Chap. 8). Separate living bodies of protobionts could have arisen earlier, but this did not become a global phenomenon of life until they began to systematically multiply, interact, and form a stable vast system with properties of self-renewal, adaptation, and evolution. The evolution of the phenomenon of life took place at the level of the system of genomes of living bodies, which was directed by the individual interactions of their phenomes with the environment (see Chap. 8). Discreteness, orderliness, organization, and unity are characteristic of both living bodies and the planetary system of life (Table 2.1). However, the basis of living bodies is a cell, and the planetary system of life consists of the entire mass of unicellular and multicellular organisms. Living bodies are closed and have boundaries, and they also have a complete form and content. In contrast, the planetary system of life is an endless mobile network that envelops the whole surface of the planet and is in a continuous process of evolution. The ability to reproduce is peculiar only to living bodies. However, this ability does not serve them, but rather the planetary system (see Chap. 9). Living bodies constantly age, disintegrate, and perish (see Chap. 11), but their descendants arise anew, constantly supporting the system of life through reproduction. Living bodies die, species of genomes die, but the planetary system and the phenomenon of life itself do not die. The death and reproduction of individuals serves the evolution and © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_15

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permanence of the phenomenon through the continuous renewal of the elements of the planetary system of life. Not a single immortal organism is known, whereas the planetary system of life has existed continuously since its inception billions of years ago. Thus, the phenomenon of life has a dual nature, combining the properties of living bodies with a short individual life and the properties of a permanent planetary system of life. Let us briefly note a number of important characteristics of these two different biological systems that make up the phenomenon as a whole.

15.2 The Nature of Living Bodies Organisms possess an individual life (see Chaps. 3–5), which is necessarily associated with a certain material body: at least, with a body of DNA or RNA; as an optimum, with a cell body; and as a maximum, with a multicellular body containing from hundreds to billions of cells. Vital properties are not possessed by individual molecules of DNA, RNA, or proteins, but only by their complex highly organized system—the cell. The part of a cell that contains a certain set of nucleic acids and proteins combined into the single structural and functional system of the nucleus or nucleoid comprises the genome. This system contains genetic material, genetic information, and mechanisms and tools for its use. The genome is an integral entity capable of manipulating substances, genetic information, differentiation, reproduction, and the construction of a phenome (phenotypic framework) around itself. The cellular phenome is a highly organized colloidal matrix comprising the cytoplasm enclosed in a membrane envelope. This is the part of a cell that surrounds and incorporates the genome within itself, forming an integral living body. Separately, they do not possess all the properties of living bodies, but united into a single system, they acquire a new quality—life. The genome is the core part of such a biosystem, since it controls the work of the entire living body, as an integral unit of life. Such a monolithic system provides and controls precise, directed flows of substances, energy, and information through special molecular channels, and controls their interaction. The life of a body is a process that takes place in time, associated with the transformation of substances and energy, based on genetic information and biochemical mechanisms (see Chap. 7). The main elements of information and the means of controlling matter are genes and their systems. The main molecular genetic mechanisms of life are replication, transcription, and translation. The emergence of these complex template mechanisms is even more mysterious than the appearance of the nucleic acids themselves. Biosystem control is based on differential gene expression and the synthesis of special proteins. Implementing the information of genetic systems via the template processes, genomes create a habitat around themselves, thereby ensuring their stable surroundings, interaction with the external environment, and continuity.

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Living organisms are cognitive systems (see Chap. 13). They are built, live, and survive on the basis of their ability to generate, perceive, analyze, and use information. The main informational advantage of living bodies is the presence of a biothesaurus— a system for recognizing and using semantic information. Living bodies are highly dynamic internally. Their existence is based on a complex network of controlled, interconnected transformations of substances, energy, and information. The life of bodies is necessarily associated with the regulated mechanisms of molecular interactions. First of all, these are the mechanisms of enzymatic catalysis (see Chap. 7) of strictly defined chemical reactions under the control of genetic programs. Enzymes enable reactions that are highly improbable at moderate biological temperatures (see Sect. 1.8). They significantly increase the rate of unlikely processes, and indeed thermodynamically unfavorable processes, which are nevertheless necessary for the cell. Reactions are directed strictly along the necessary metabolic pathways, which automatically cuts off billions of unnecessary processes. Bodies, mechanisms, processes, and functions are products of the deterministic self-organization of matter into biological systems under the control of genetic information and information from the surrounding world (see Chap. 5). As a result, ordered biosystems are formed, existing on the basis of the principle of stable disequilibrium, supporting themselves and constantly working against the increase in entropy. The state of life is a special emergent state of a specially organized biological system. Living bodies have a discrete multilevel organization. The high level of orderliness of the internal contents is what underpins the vital properties and activity of organisms. The creation and maintenance of orderliness in living bodies, the implementation of all the relevant processes, and the use of information are accompanied by the mandatory consumption, transformation, and targeted use of energy. The thermodynamic basis for the existence of living bodies is the potential for thermal motion of molecules (see Chap. 7). On the one hand, molecular motions lead to the destruction of the ordered state (increase in entropy) and the creation of structural instability. On the other hand, they determine all the various interactions, processes, and mechanisms for maintaining life. This contradictory inner duality, synchronous destruction and restoration, is one of the basic properties of living bodies. Such a disequilibrium is a condition and a driving force for the flow of continuous controlled processes in living systems, directed against destruction and towards the performance of useful work. The internal contents of cells are so discrete and dynamic that they can be considered, not so much as bodies, but rather as continuous processes. Constantly occurring biochemical, biophysical, and physiological vector processes directed against internal and external forces of dissipation constitute the basis of the “vital force”. They temporarily compensate and balance the disturbing forces of nature, thereby ensuring survival, but also perform useful work, determine functions, and ensure the recreation of living bodies. Only constant opposition from cells to the steady growth of entropy can sustain life. Life originated, developed, and exists only in the presence of a liquid aqueous medium, which is an internal “ether” that integrates everything in living bodies (see Chap. 8). Any organism living today is derived from organisms that lived before it. Or

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rather, every living genome of any organism is a derivative of the genomes that lived before it. Each is a link in an endless chain of evolution, stretching through billions of years to the present moment. This chain is rapidly continuing its development, towards a hard to imagine and unpredictable future. Living bodies are capable of variability, adaptation and survival, but only exist for a genetically limited time (see Chap. 11). Death is an inevitable event for all organisms, without exception. The existence of any living body lasts only an instant compared to the billions of years of the immortal phenomenon of life on Earth. Death is a genetically determined, hereditary phenomenon in the life of every organism, and it is an inevitable natural event after a certain period of time. Death is tragic for living bodies, but does not matter for their genomes, and it has a positive impact on the populations and species that make up the planetary system of life. The lifespan of species of genomes is virtually unlimited in comparison with their individual components. As a result of replication and division, their new representatives continue to live in other bodies without any significant changes. Individual living bodies are just temporary phenotypic shells that the genome uses once for its immortal purposes. Organisms exist only as an integral part of the Earth’s ecosystems. Living bodies are semi-autonomous open self-repairing systems interacting with the external environment through the selective consumption of substances, energy, and information. Based on the genetic programs of their genome, they assimilate the necessary substances and energy, renew their molecular composition, and emit heat and chaos, which enables them to maintain orderliness and autonomy for a relatively long time. The life of organisms proceeds along two dimensions (see Chap. 17). There is a continuous genotypic life, hidden from our eyes—a set of processes of existence and functioning of all elements of the genome and the realization of its information potential during the continuous change of generations; and there is a visible intermittent phenotypic life, which is a manifestation of the genome in the form of living bodies. The “discontinuous continuity” of genomes and “continuous discontinuity” of phenomes are based on the cycles of copying of nucleic acids, proteins, and intracellular ordering in the processes of reproduction and development. The increase in entropy and based on it variability are spontaneous and inevitable. In order to be stable and not disappear, living organisms and their genomes need to constantly struggle against entropy, and this is possible only for a certain time. Therefore, for the reliable and long-term existence of the planetary system of life, it is necessary to systematically reproduce copies of themselves. The continuity of the existence of biological species is ensured by reproduction (see Chap. 9) and recycling of their permanent genomes via the constant exchange of living bodies and the change of generations. The process of reproduction ensures the transmission of genomes. Cells carry out transcellular transfer of genomes, and multicellular organisms carry out transorganismic transfer of genomes, guaranteeing the permanence of the phenomenon of life. Genomes have conservative variability, which, on the one hand, supports the long-term existence of an unchanged species, and on the other hand, through reproduction and generational change, ensures the processes of their adaptation, development, and evolution.

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From the point of view of a bystander, life is an intermittent process of the existence of living bodies, the task of which is their own survival and reproduction. However, in essence, organisms are only carriers of the permanent genome, just ensuring its survival and reproduction. It is only for this purpose that living bodies have a significant armoury for survival and reproduction, which we perceive as properties of living beings. Each time the carrier of life is recreated anew using the genome, which, practically unchanged, travels unremittingly from one body to another. Individual bodies manifest themselves as just one of the stages of infinitely repeating cycles of transformation and development of discrete genomes. Based on the primacy of genomes in relation to their bodies, we can say that our planet is inhabited by diverse species of genomes that build bodies around themselves; bodies which are adequate to various habitats (see Chap. 2). Or, one might say, bodies which are adapted to extract matter and energy from various sources on Earth. Living bodies have a set of properties that distinguish them from the inanimate. It is impossible to name any one property that determines the living. It is the complex of properties that determines a qualitatively new state of matter. Based on this complex, living bodies have a variety of functions and means that contribute to their survival. Hence, a permanent genome in a temporary phenotypic framework is the basis and reason for the existence of living bodies as autonomous carriers of individual life. The purpose of these individual lives is the reproduction of their own kind, but not of themselves, whereas the purpose of the reproduction of genomes is the reproduction of themselves as near to exactly as possible through exploitation of the living bodies in which they live. Then, the purpose of the reproduction of individuals is to maintain the qualitative and quantitative composition of their species of genome. Consequently, the purpose of the existence of an aggregate of living bodies is constant mass reproduction of genomes to ensure the existence of the planetary system of life. That is, living bodies are not the ultimate goal of life, but only a means of reproduction of immortal genomes.

15.3 The Nature of the Planetary System and the Phenomenon of Life Life is an integral phenomenon, although it is represented by an infinite number of discrete units of living bodies that possess individual life and constitute the planetary system of life. The phenomenon of life is a complex emergent property of biological systems that is not characteristic of any of their constituent parts, but appears only when all these parts come together. It is obvious that the program and means of structuring the surrounding material space into various forms of living organisms are the systems of genes of DNA molecules. Countless different DNA molecules contain lots of “actual” (known to be capable of expression) and a truly huge amount of “potential” (as yet poorly

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understood functionality, but with the potential for realization) genetic information. Functioning individually or in various combinations in different genomes, they specifically structure the surrounding material space, creating specific phenotypes in the form of individual representatives of millions of species of living organisms with their own individual lives. They are interconnected and function inseparably, forming the vital informational and material field, linking all the living into the planetary system of life. This indicates the integrity of the planetary system of life as a planetary phenomenon, despite its duality and discrete forms of manifestation. Thus, the essence of life is the process of continuous existence in the development of very stable dynamic complexes of various genomes. They contain specific programs for the controlled ordering of the surrounding material space and create certain manifestations of their existence in the form of specific living bodies. Consequently, the phenomenon of life is a permanent process supporting the existence of an evolving system of genomes in various manifestations of their phenotypic (bodily) frameworks. The strategic goal of such an organization of the planetary system of life is the correspondence between the genome system and the diverse environment of the Earth through a system of qualitatively different phenomena. Life is a process. It is like a perpetual motion machine of the second kind—a kind of process which, once set in motion, continuously turns almost all the energy extracted from the Earth’s environment into work. This machine has been operating for several billion years, not only without losing its internal energy, but even increasing it. Furthermore, it will continue to work indefinitely as long as geophysical conditions for the existence of living bodies remain on Earth. Living bodies are the building blocks of this stable thermodynamic system of life. They are a direct tool for extracting and transforming matter and energy. Basically, living bodies organize and direct the chaotic thermal motion of matter as a temporal support for themselves and an eternal support for the system of life. The concept of processualism of life emphasizes the essence and logic of the phenomenon itself, its continuous dynamism, and the significance of some of its manifestations. It reveals the meaning of successive changes in the states and stages of development of living bodies and the planetary system of life. It also contributes to our understanding and perception of the phenomenon of evolution as a process of continuous development. It becomes obvious that the present geophysical and biological period in the history of life is only a snapshot of the ongoing process of joint development of the Earth and its biological envelope. Consequently, the planetary system of life is constantly evolving, that is, it is constantly in the process of prolonged, progressive, interrelated changes in genomes and living bodies in accordance with certain laws of internal development and under the influence of the forces of the external environment. The principle of processualism and continuity of the development of life results in gradual improvement and adaptation of the resulting generations of organisms, which ensures the homeostasis of genomes for millions of years under almost any conditions suitable for the existence of proteins. From this point of view, evolution is a global property of the system of genomes, which is directed and realized through the individual interactions of their phenomes with the environment.

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Understanding the naturalness of the process of evolution as a general property of Nature helps us to become aware of the inevitability and expediency of the death of individual conservative living bodies, through the need to modify their genomes and build a phenotypic framework that is newly adapted to "feed" on the planet (see Chaps. 11 and 12). Comprehension of the duality of individual life (genome + phenome) gives an understanding of the illusion of death, which only leads to the expiry of the phenome, whereas the immortal genome just moves on into a new body. Comprehension of the duality of the phenomenon of life (living bodies + planetary system of life) helps us to understand the true meaning and significance of the ability of living bodies to reproduce, which serves not the individual, but only the system. The unified planetary system of life is a network that covers the surface of the planet. The phenomenon of life appeared as a system of genomes in discrete forms of phenotypic framework, capable of death and rebirth (see Chap. 8). They formed a stable system (a kind of an organism) with fundamentally new properties. First of all, the ability to extract matter and energy from the planet for their own existence. Thus, life became permanent from the moment of the emergence of a highly organized stable system of reproducing living bodies, constantly “gnawing” at the planet. It becomes clear why the phenomenon is also firmly attached to the planet Earth. Individual life is always tightly connected with a specific body. The permanence and evolution of the phenomenon of life are based on the principle of consistent obligatory replacement of the elements that compose the planetary system of life. That is, living bodies must certainly perish and give up their place to the subsequent, improved generations. Cyclic reproduction of genomes and their continuation in offspring is a prerequisite for the endless process of the phenomenon of life. Reproduction is an important property of living bodies (see Chap. 9), the result of which does not belong to them, but to the planetary system of life. The eternity of this system is determined exactly by the exchange of living bodies— inevitable death and continuous reproduction of the elements of the system (see Sect. 9.7). Reproduction of organisms provides the basis for the processes of their adaptation, variability, heredity, and evolution. This is the foundation of the global evolution of the planetary system of life. That is, the mechanism of reproduction enables the phenomenon of life to overcome its gradual structural and organizational degradation. At the same time, organisms do not reproduce themselves exactly, but generate organisms similar to themselves. No living thing is able to reproduce itself anew or become immortal. Nature ruthlessly destroys the carriers of life, but gives them enough time to ensure reproduction and transfer of their genomes to subsequent generations. In turn, this enables the long existence of biological taxa. The goal of reproduction and evolution is not the survival of organisms and species, but the survival of genomes and the biological information they contain. Mortal living bodies are only a means of maintaining the continuous process of life on Earth. They are intermediate products of the process of global exchange of matter and information within the planetary system of life. The limit of existence is characteristic for all organisms, but not for the phenomenon of life. For a species of a genome, the lifespan of a carrier does not

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matter. Science does not know a single immortal body, but the unified system of life has existed continuously for billions of years. The ability to survive and the phenomena of aging and death are inherent features of living bodies, but not of the phenomenon of life. Organisms inevitably perish, but each time arise anew, whereas the planetary system of life arose many hundreds of millions of years ago, does not age, does not die, and does not arise anew, but is engaged in a process of constant development. The death of individuals serves the immortality of the phenomenon, since it is one of the conditions for the continuous renewal and evolution of the elements of the planetary system of life. For billions of years, the essence of life has not changed. It is only the phenotypic frameworks that change, as in a kaleidoscope. Living bodies and the planetary system of life evolve progressively, but they will inevitably perish. However, this will not happen any time soon, but only when conditions are reached on Earth that are incompatible with the existence of aqueous solutions of nucleic acids and proteins. This may happen in about 5 billion years due to the transformation of the Sun into a red giant and its absorption of the Earth. Consequently, the process of the development of life on Earth is somewhere midway along its path, and is only a tiny element in the Great Process of Movement.

Chapter 16

Matter and Information

It is obvious that living bodies are made of substances. But this is only one aspect of their existence. It has now been established that information plays an equally important role in their lives. The variety of substances that make up organisms are well known (see Chap. 1). These are proteins, nucleic acids, water, carbohydrates, fats, and many other constituents. They are concentrated in the microvolume of cells in an orderly way and interact in an organized manner under the control of genetic information (see Chaps. 13 and 14). As a result of the informational organization of matter into the ordered structures of cells and organisms, the flows of substances and energy are directed strictly along certain paths, maintaining individual life at a controlled rate. DNA in the genome is a perceptible material structure, which records an enormous mass of impalpable information. That is, DNA is also of a dual nature. It is both the material and the informational essence of life. Living bodies are dissipative structures that spontaneously disintegrate under the action of work and thermal motion. This stream of thermal destruction has potential, non-directional energy. Spontaneous destruction and directed restoration are another duality in the driving force of life (see Sect. 7.4). Bioinformation plays a role in directing chaotic flows of matter and energy into self-organizing systems. Regulation of the rates and direction of these flows is carried out using special tools organized by the genome, including proteins and enzymes, as well as structures, mechanisms, methods, and algorithms for their interaction with other molecules. The initial, or initiating, information about the proteome is contained in the DNA of the genomes. The implementation of this information in the process of transcription gives the impetus for the multiplication of information, and indeed a cascade of distribution of that information. A new type of information carrier appears in the form of RNAs, carrying new potential and new informational content. This in turn causes a new round of multiplication, transformation, and dissemination of information in the process of expression. This leads to the emergence of the next carrier of information, namely, structural and functional proteins, which have colossal potential and physicochemical bases for using this information for the manifestation of traits © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_16

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and the appearance of structural (phenotypic) information in the form of organized organic molecules, enzymes, cytosol, and organelles. Hence, at the protein level, genetic information is transformed into phenotypic information. Here, an element of genetic information, a gene, turns into an element of phenotypic information, viz., a protein. This is a new level of information potential in biosystems, bringing into being many variants of intracellular structures and an infinite variety of cells and multicellular organisms. The double nucleic acid–protein essence of life is yet another duality. Life is an endless series of transformations of two classes of chemical compounds—proteins and DNA and their accompanying information (see Sect. 13.7). Thus, besides the great importance of genetic information, which is realized in living bodies through a multistage expression process, the accompanying phenotypic information, associated with the gradual appearance of new structures, is also extremely significant. Transformations of information also accompany a variety of biophysical and biochemical transformations of substances. For example, during the biochemical reactions of protein synthesis in cells, it is not only the material transformations of DNA → RNA → protein that occur, but the information recorded in genes is also modified, transferred to another carrier, and then used to form polypeptides. Genetic information is also of great strategic importance for the planetary system of life (see Chaps. 13 and 14). It gives rise to individual lives that make up a giant material biological system—the phenosphere. The collection of information from discrete genomes of all living bodies on Earth forms a single bioinformation space— the genosphere. A constant circulation of genetic information is maintained within the genosphere. This circulation necessarily goes through individual organisms and their genomes, which are tools for working with matter, energy, and information. Information also circulates within the global genome at the level of replication, transcription, transgenesis, hybridization, and recombination. And within the global phenome, material flows are represented by an intermittent continuity of diverse individual living bodies, which are the phenotypic manifestations of the information contained in the genomes. In this case, the genome controls these processes by creating certain structures and synthesizing specific enzymes that distinguish and direct flows. Therefore, information determines life and controls it through the direction of the flows of matter and energy through functional systems, as well as through the control of the rates of these flows and the limits of their distribution. As a result, a specifically organized materialization of space and the manifestation of information in the form of certain living bodies is realized as the phenomenon of life. Thus, life is a special form of coexistence of matter and information. The immortality of the phenomenon of life lies in its dual nature. Despite the fact that the material component of living bodies wears out and perishes, the non-material substrate of life in the form of genetic information is not subject to aging and death. Information, together with the genome, travels from one body to another, causing the reconstruction and continuity of life.

Chapter 17

Genomes and Their Bodies

17.1 The Cell is for the Genome In connection with the exceptional importance of the genome as presented in this book, the cell may be looked upon from a different perspective, not from the point of view of its primacy for life and its existence in itself (the cell is the basis of life), but regarding it as “serving” the center of control and reproduction of life, the genome itself (the genome is the basis of life). Certainly, the cell is a monolithic structure in which all structures and processes are interconnected, and it is impossible to draw a clear line between genome and phenome. But there are a number of facts that still speak for the primacy of the genome in relation to this framework: • There are no fully-fledged cells without a genome. Modified variants of cells without a genome, for example, erythrocytes or platelets, are just derivatives which immediately lose the ability to self-repair and multiply. However, the genome itself can exist for a long time almost autonomously, retaining the potential for reproduction, for example, in the form of spores, viruses, plasmids, and vibrios, without having a fully-fledged cellular setting. • During mitosis or meiosis, cells lose their typical organization and function completely: organelles are reduced, the nucleus disappears, and the mixoplasma, chromosomes, and division apparatus form (see Chap. 9). They structurally and functionally fill the entire inner space of a dividing cell. That is, the modified genome completely “occupies” and uses the entire volume of the former cell for its own purposes. The cell actually ceases to exist, even before the division, and its internal space is completely subordinate to the interests of the genome. • When somatic nuclei are cloned and transplanted into a denucleated egg with subsequent fertilization, an organism develops on the basis of the genetic information of the somatic nucleus and sperm. The information of the denuclearized egg remains practically unmanifested. • One and the same genome can be the source of dozens of different cells, tissues, and organs in multicellular organisms. A single species of genome can form © Springer Nature Switzerland AG 2023 G. Zhegunov and D. Pogozhykh, Life. Death. Immortality., The Frontiers Collection, https://doi.org/10.1007/978-3-031-27552-4_17

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several different living bodies, living in different environments, with different body parts, organs, functions, and metabolism, as happens, for example, in many metamorphosing insects (Fig. 11.2). That is, it is the genome that is the source of its diverse phenotypic frameworks in the form of different cells, different organelles, different types of cytoplasm, and different organisms. During reproduction, it is the “conserved” genome, in the form of a haploid set of chromosomes and several DNA-dependent enzymes, that is passed on to subsequent generations. The development of a new cell, or a new organism, begins with the formation of a fully-fledged diploid genome and its differential expression. “Embryogenesis recapitulates phylogeny.” This law indicates that a single zygote genome is the source of thousands of different cells, tissues, organs, organisms, functions, and types of metabolism that existed in thousands of different dissimilar ancestors millions of years ago and have survived to this day. Damage to the phenome is not inherited, but the slightest transformation of the genome or its mutations is manifested by significant phenotypic modifications of the offspring. Genomes exist at the cytogenetic level, using cellular mechanisms for their own reproduction and distribution. They live in the cells of different living organisms and travel easily from one cell to another or from one organism to another, and can even exist for a long time outside organisms without any manifestation (gametes, spores, seeds, etc.). So which is more important: the genome or the phenome? To answer this, we will try to answer the question: what is the main period of existence of living bodies in the cycles of individual development. For example, in the May beetle, which is more important: the egg, the larval stage, which lasts up to 5 years, or the adult stage, which lasts 1 month (Fig. 11.2)? Or in the liver fluke, which has 5 stages of development in the form of different living bodies (Fig. 18.1). Which is the main stage? Slime molds can live in the form of a multinucleated plasmodium, or they can live in the form of numerous unicellular creatures. Which is the main stage? It seems impossible to answer. Nevertheless, all of the above cases are reduced to a common denominator if the genome is recognized as an integral part, and indeed the main part, of all the listed stages and states. That is, all the listed bodies are just a shell behind which the genome is currently hiding. In all cases, the genome is the main character, determining all the possible types of its phenotypic framework. The genome of the species never disappears, despite the death of cells and living bodies. In the processes of the cell cycle or ontogenesis of individuals, it can change ploidy, disintegrate into separate chromosomes, divide, move to new habitats, and unwind into the chromatin network and start all over again in its new “cell”.

This list of facts indicate the leading role of the genome in its interdependent existence with the cell and the organism. After all, it is the genome, through the differential expression of information, that carries out reproduction and development, and controls almost all cellular processes. And the cell acts as an autonomous

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specialized microspace, as a living barrier and an executive system of the genome that controls life.

17.2 Dual Unity of Genome and Phenome Living organisms are fundamentally different from inanimate objects, machines, and complex constructions in that they have not only a set of special structures and functions (phenomes), but also programs for the manufacture of their own kind (genomes). Moreover, these programs can repeatedly duplicate during DNA replication cycles and get transmitted from generation to generation during reproduction, then become realized in corresponding phenomes through molecular mechanisms. Inanimate objects, one might say, also have a kind of “phenome”, namely, the set of features that characterize their shape, structure, size, etc. But they do not have anything similar to a “genome”, as internal programs of reproduction, development, functioning, and maintenance of integrity. Only the most complex programmed robots created by man, computers and their systems, contain a material part and a software part, similar to the phenome and genome. However, such machines still do not contain programs for self-recovery, reproduction, and development, and so are not capable of self-reproduction, maintenance of integrity, and evolution. All representatives of the living world have such programs recorded in the genetic material of their genomes (Chap. 14). The genome is a collection of specialized genetic information and tools for its use (see Chap. 13). The genomes of representatives of different species contain a different qualitative and quantitative composition of genes. A range of structural proteins and enzymes, as well as the highly organized environment of their localization, are important attributes of the genome. The presence of a genome is the ultimate necessary condition for self-renewal and reproduction of representatives of all kingdoms of organisms, from viruses to mammals. That is, the genome is a coded program and a mechanism for its transmission, necessary for the reproduction and development of new individuals, as well as for maintaining their structure and functioning (in other words, for the formation and maintenance of a certain phenome around itself). The phenome is the totality of all properties and characteristics of cells or an individual. This includes size, shape, presence of limbs, features of metabolism and functions, features of behavior, and much more. The phenome of any organism is primarily built on the basis of proteins, which are in turn encoded in the genome. That is, the basis of the phenome is proteins, and the basis of the genome is nucleic acids. The close connection between them goes through the molecular mechanisms of implementation of genetic information and its transformation into traits. These are mechanisms such as replication, transcription, translation, expression, and a number of others. Thus, a living organism is not only a genome and a phenome, but also a set of molecular and cellular processes and the mechanisms that connect them. Genomes and phenomes are interconnected by the processes of functioning, reproduction, and development. In each cycle of reproduction of living bodies, the genome

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implements information in the phenome, which provides the conditions for their coexistence. This in turn creates conditions for the subsequent stage in which the genome is reproduced. In this connection, the primacy of the genome in relation to the phenomenon is obvious. The phenome serves as a phenotypic framework, a phenotypic envelope or habitat which the genome uses once for its own selfish purposes. Living bodies do not need additional information from the environment to be themselves. As Fritjof Capra and Pier Luigi Luisi noted, “…all information needed for a fly to be a fly is contained inside the fly,” which also reflects our idea of the unity of the genome and the phenome in an integral living body. The reproduction cycles of the genome and phenome are repeated many times, which has ensured their interconnected and interdependent existence for millennia. Moreover, a phenome cannot be reproduced without a genome, and vice versa. This demonstrates the basic dualistic informational-material principle of organization of living bodies. That is, any organism contains both a genetic program and its product in the form of itself .

17.3 Species of Genomes Representatives of some biological species can exist in the form of completely different bodies during their life cycle. This phenomenon is known as polymorphism. Here, the individual forms of “phenotypic framework” of the same genome can have different sizes, shapes, functions, and internal content based on its differential expression. They contain various differentiated cells, tissues, and organs. They can live in different environments. This means that one and the same genome can exist in the form of completely different bodies! It turns out that a certain living body is a specific manifestation of the phenotypic framework of the genome at a certain stage of development. Consequently, we can talk about the possibility of the existence of representatives of this species of genome in the form of different bodies, each with its own individual life. For example, the genomes of some parasitic flatworms manifest very bizarre forms of existence. In particular, the life cycle of the liver fluke Fasciola hepatica is associated with the existence of several completely different living bodies (Fig. 17.1), inhabiting completely different environments: (1) A sexually mature form, as a flatworm that lives in the liver of cattle and small ruminants. (2) As an egg, in a waterbody. (3) As a larva, Miracidium, that lives independently in a waterbody. It actively penetrates into the body of an intermediate host, a small pond snail. (4) Miracidium lives in the body of the pond snail, where over time it transforms into the next intermediate stage, a sporocyst. (5) A new larval generation of living bodies, redia, develops parthenogenetically from germ cells in the sporocyst. (6) Another generation of larval bodies, cercariae, is formed from redia. They exit the mollusk and actively move in the water. (7) Cercariae attach to the stems of plants around the waterbody, become covered with a shell and form adolescaria. (8) Swallowed by animals together with

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Fig. 17.1 Derivative living bodies of the species of genome of Fasciola hepatica. Variants of differential expression and phenotypic products of one species of genome. If you scoop up water from a pond, it may contain organisms that can be mistaken for different biological species of animals. However, they are all variants of the phenotypic framework of a single species of genome. Explanations in the text

grass, they get into the animals’ blood circulation and enter the liver, where they develop into a sexually mature form of Fasciola hepatica, called marita. Astoundingly, all these diverse bodies, each with its own individual life, are the derivatives of one and the same genome! A genome that seeks to adapt, survive, and multiply, and for this purpose, creates such bizarre bodies, which, apart from DNA, have nothing in common. This leads to the conclusion that one and the same genome can be the source of several completely different phenomes. Obviously, very different information can be extracted from the same complex of DNA molecules of a single genome to generate a diversity of living bodies. Such plasticity of the genome is also characteristic of many other creatures, such as insects that develop through metamorphosis. It turns out that the same biological species of organisms can exist in the form of different bodies! That is, in this case, a particular living body is a specific manifestation of the phenotypic framework of a specially differentiated genome at a given stage of its (genome’s) life cycle. Therefore, it is not entirely correct to speak about the existence of a given biological species of organism. It is better to talk about the existence of a given species of genome, which can exist in different forms of phenotypic framework. For example, the species of genome of Fasciola hepatica, as described above, can exist as: eggs, miracidia, sporocysts, redia, cercariae, adolescaria, and marita (Fig. 17.1). Clearly, from the standpoint of biological systematics, it would be more correct to speak, not of the existence of the biological species of Fasciola hepatica, but rather of the existence of a species of genome of Fasciola hepatica. This point of view assumes that various organisms can have different cells, tissues, and bodies, live in different environments, have different metabolisms and functions, and yet at the same time be derivatives of one and the same genome. Moreover, all these forms of bodies are

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absolutely functionally equivalent for a particular species of genome, since in any case, they serve its adaptation to a specific habitat. The above example of Fasciola hepatica concerned hermaphrodite organisms, but polyphenotypic genomes are also characteristic of dioecious organisms. For example, the adults of the May beetle Melolontha melolontha exist as males and females. But their species of genome can exist in the form of an egg, a larva, a pupa, and adult imago organisms of both sexes (Fig. 11.2). Similar considerations apply to individual unicellular organisms with complex developmental cycles. For example, the life cycle of the species of genome of malaria Plasmodium vivax takes place in the bodies of two different hosts—a mosquito and a human, where the protozoa have completely different phenomes, live in different tissues, and reproduce in different ways. In the life cycle of the malarial plasmodium, a person is an intermediate host (tissue schizogony, erythrocytic schizogony, the beginning of gametogony), and the malaria mosquito is the final host (completion of gametogony, fertilization, and sporogony). That is, the species of the Plasmodium vivax genome can exist in a variety of guises. The phenomenon of polymorphism, which is the formation of different cells and living bodies on the basis of one and the same genome, can be called genome polyphenotypicity. This is due to the ability of the genome to be differently determined, differentiated, reprogrammed, and expressed, depending on the stage of development and environmental conditions. Moreover, this does not depend on the karyotype, gene, or allelic composition of a genome, as they remain unchanged in all cases. Fundamentally, the genomes of all sexually reproducing organisms are polyphenotypic, since at a certain stage of development they can be in the bodies of haploid male and female gametes (spermatozoa or eggs), which have different phenotypic frameworks. In addition, dioecious representatives of such species are divided into males and females, which have phenotypic differences. This is defined as sexual dimorphism. Males and females can be very different in size, color, features of functions and anatomical structure, the presence of special organs, body parts, etc. Therefore, they can sometimes be mistaken for individuals of different biological species. For example, the male blanket octopus (Tremoctopus violaceus) is one hundred times smaller than the female and has no webbing between the tentacles. It can easily be perceived as an organism of a different biological species in comparison to the female. However, they are both derived from the same species of genome. Can the intermediate bodies of development of one genome transform into an independent biological species, that is, an independent species of genome capable of evolution? Yes. For example, the larvae of ascidians brought about the emergence of chordates. Moreover, this was a leap in the evolution of the planetary system of life. This example indicates yet another possible evolutionary mechanism for the phenomenon of life. We are accustomed to living in the world of men and women; we consider the differences between them to be natural to the point that we no longer really “notice” them. Still, there are significant phenotypic differences between tough males and beautiful females (Fig. 17.2). But they possess the same species of genome, that of Homo sapiens.

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Fig. 17.2 Different phenotypic manifestations of the species of genome of Homo sapiens in the form of two mature organisms of the opposite sex. Albrecht Dürer’s Adam and Eve, 1504

We are quite confident when we talk about the existence and evolution, for example, of some biological species of insects on Earth over hundreds of millions of years, which has been proven by paleontology, although it would be more correct to say that a specific species of genome has existed during this period, gradually evolving and changing its phenotypic framework. Its carriers are constantly changing, but the genome remains fundamentally the same. This also justifies the more equitable reference to the genome of a certain biological species of organisms as a species of genome. A biological species, as a taxon, is the basic structural unit of the planetary system of life. The structure of the entire taxonomic hierarchy of life depends on this unit. However, in modern science there is still no unified understanding of the essence of a biological species. Therefore, based on our considerations, the taxonomy of

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living bodies on Earth should additionally take into account the noted property of polyphenotypicity of a species of genome. Thus, our planet is inhabited by a great diversity of the species of genome that build around themselves bodies adequate to all kinds of habitats.

17.4 Global Phenome and Global Genome All Living bodies on Earth form an aggregate, which we define as the global phenome (see Sect. 2.6). This is a gigantic open system, consisting of countless individuals, representatives of the species of all kingdoms of living beings living on Earth. This system can be called the phenosphere. It is unified by its protein basis of structure and functioning. The global phenome continuously consumes matter and energy from the environment in order to maintain its organization. This discrete system is constantly being destroyed, since each individual representative has a limited lifespan. However, the global phenome retains its structure and even develops, due to the fact that individuals leave offspring. Reproduction, along with the subsequent exchange of living bodies and the change of generations, continuously work against the increase in entropy in the global phenome system (see Chap. 9). The global phenome is a product of the expression of the global genome. In other words, this is the genosphere, which is represented by the entire set of countless genomes of individuals of all species living on our planet. This is also a kind of system; an open system, interacting with the environment through its own phenotypic patterns that we have not yet fully understood. This discrete system is unified by the universality of the nucleic acid structure, as well as by the principles of recording, storing, and realizing genetic information. It is combined into a single whole on the basis of constant, vertical and horizontal circulation of genetic information (see Sect. 14.10). Material carriers of information throughout the whole global genome system are special carriers of individual genomes in the processes of reproduction, together with various mobile genetic elements. That is, the essence of the existence of the global genome system is continuous molecular information processes, continuous transfer of genetic information within and between discrete genomes (information circulation), and continuous transfer of discrete genomes from one body to another. The global genome and global phenome are fundamentally different systems, but both systems of life are nevertheless inseparable from each other and form an integral phenomenon, which is the basis of the unified planetary system of life. Countless phenotypic representatives and various species of living organisms have existed over the billions of years of development of nature. Moreover, there were long periods when the global phenome almost completely disappeared off the face of the Earth, e.g., after collisions with large astronomical objects. Only prokaryotes and small eukaryotes remained in the depths of the ocean and the Earth. However, the basic essence of life remained practically unchanged. All the same molecules of nucleic acids and proteins remained, as did the same principle of recording and

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realizing information, and the same molecular mechanisms of replication and transcription. Then, over millions of years of evolution, the extensive network of the global phenome was restored, gradually filling various biotopes. But this restoration has been accomplished with completely different species of organisms, since evolution chooses different paths according to the circumstances. That is, for generations, the essential features of the global genome systems have gone on practically unchanged, while the global phenome system has experienced constant and substantial fluctuations. Probably, the phenomenon of life first appeared as a phenomenon of genotypic life (see Sect. 17.5), without a pronounced phenotypic manifestation, in the form of replicating nucleic acids in some amorphous colloids. Further, under certain conditions, various combinations of functioning nucleic acids and proteins began to purposefully improve their environment for adaptation and survival with a “phenotypic framework” that was varied depending on living conditions, methods of nutrition, metabolism, movement, etc. This is how phenotypic life gradually appeared, first as a system of various prokaryotes, then unicellular eukaryotes, and then multicellular organisms. All of them possess autonomous bodies that mediate between the genome and the external environment. In this way life assumed the form usual to our perception. We perceive only an obvious change in the representatives of phenotypic life, intermediaries between the global genome and the changing external world. And we do not perceive genotypic life, since it exists in the processes of replication, transcription, translation, and many other molecular mechanisms hidden from our eyes, which determine the existence of the living bodies we see. Hence, the planetary system of life consists of interconnected, interdependent, and interpenetrating systems of the global phenome (the phenosphere) and the global genome (the genosphere), which contain flourishing genotypic and phenotypic life.

17.5 Phenotypic and Genotypic Life The life of organisms is a discrete, intermittent process. One set of individuals is inevitably replaced by others. Generations are continuously replaced by the next. The change of generations and the carriers of genomes themselves are dramatic events in the process of the existence of living organisms. However, during their temporary existence, in the process of reproduction, individuals pass on the genetic program for the development of their own kind to the next generation. Those in turn grow and mature based on the DNA programs, then multiply again, beginning a new round of life. And so continuously, as long as there are conditions for the survival and reproduction of organisms. Such a successful continuity of the existence of consecutive generations of living bodies is ensured by the presence of their genomes, the genetic programs and mechanisms of reproduction, development, and survival. The continuity of genetic material and information over time, despite the change of generations, is one of the main characteristics of living things (see Chap. 18). This is ensured by the permanence of the existence of numerous genomes, despite

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the mortality of their carriers. Living bodies have time to either multiply, or create a transitory form of life in the form of gametes, spores, cysts, or other very stable formations containing the conserved genome. That is, the appearance of an organism is, one might say, an act of manifestation of the creative informational potential of the genome. Figuratively speaking, by analogy with mushrooms, one can imagine individual organisms as “fruiting bodies” appearing for a while on the body of the permanent “mycelium” of a similar branched network of the global genome (Fig. 17.3). Organisms exist only for a limited time and will inevitably die, while the network or system of genomes on our planet is virtually immortal. The task of short-lived fruiting bodies/individuals is to massive produce and distribute genomes, while maintaining the homeostasis of the global genome and enriching it with new qualities. Thus, the course of the process of life in the planetary system goes on in two dimensions. One is the continuous genotypic life hidden from our eyes, as the set of processes and functioning of all genomes and the realization of their informational potential. And the other is the visible intermittent phenotypic life, as the set of processes of existence and functioning of living bodies. One can regard any separate living organism, for example—a mouse, from this point of view. It possesses a set of well-manifested phenotypic characteristics of phenotypic life. These are, for example, the size and shape of its body, its weight, the presence of four limbs, and so on. The actual existence and functioning of the living body of a mouse, with all its traits and characteristics, constitutes the essence of its phenotypic life. In addition, it is obvious that a mouse also has genotypic characteristics. In particular, there is the presence of a species-specific karyotype, certain nucleic acids, genes, and proteins, and also the principles of organization laid down by a specific genome. There are also the enzymatic processes of replication, transcription, translation, and

Fig. 17.3 Organization of a mycelium and its derivative fruiting bodies as a model for the genomic network on our planet. A—A mycelium that forms a network of filamentous hyphae (as an analogy for genotypic life), which forms the fruiting bodies (as an analogy for phenotypic life). B—By analogy with a mycelium, one can imagine the presence of a permanent branched multicomponent network of species of genomes on Earth (the global genome with its genotypic life), showing its potential to form different “fruiting bodies”, or individuums (which determine the phenotypic life)

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many other molecular processes for manipulating with information. The actual existence and functioning of all parts and elements of the mouse genome, as well as the realization of its creative informational potential, is the essence of its genotypic life. For a better understanding of the dual nature of life, one can also draw an analogy between a living body and a personal computer. A computer has a complex system for manipulating information (processor, memory, programs, files, etc.) and a system for visualizing information in the form of perceived images on the monitor. We do not see the complex inner workings of a computer system, but we perceive its consequences in a “materialized” form on the monitor. A living body also has a system of genomes that imperceptibly operate on information, and its material embodiment is presented in the form of the various visible characteristics of an integral living body. Proteins link and unite both levels of life: genome → proteins → phenome. Genomes and proteins (with all molecular mechanisms) belong to genotypic life, and living bodies built using proteins belong to phenotypic life. The unifying molecular mechanisms are replication, transcription, and translation. They start the chain of enzymatic, metabolic, and physiological processes, providing all the properties and potencies of living bodies. Thus, the proteome has an undeniable central role, as a link between the genome and the phenome in living bodies. It is proteins that constitute the common component of the two levels of life. On the one hand, proteins provide the molecular genetic mechanisms and processes of the genome; on the other hand, proteins are the key constituent parts of organelles, cells, and organisms, providing for all their properties and functions. Genetics is a complex science that studies genotypic life. It brings together a group of disciplines such as general genetics, cytogenetics, molecular biology, bioinformatics, and others related to the comprehensive study of the genome. One might therefore say that phenotypic life is studied by the complex science of phenetics. This unites a group of disciplines such as anatomy, physiology, cytology, histology, and others related to the complex study of the phenotype of living bodies. Hence, the life of bodies has two interconnected components: phenotypic life, which is the set of structures and processes making up the vital activity of organisms, and also genotypic life, the set of processes involved in the functioning of genomes and genetic information.

17.6 Summary The duality of the phenomenon of life is obvious, since on the one hand there are actual living bodies, and on the other, there is a planetary system, which has another set of properties. All genomes of the planetary system are unified by the common nature of nucleic acids into the single system of the global genome, and all organisms are unified by the singular nature of proteins into the system of global phenome.

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The planetary system of life consists of the interconnected, interdependent, and interpenetrating systems of the genosphere and the phenosphere, within which flourishes genotypic and phenotypic life. The cell serves the genome, not the other way round. The cell acts as an autonomous microspace, a living barrier, and an executive system for the genome that controls life. One and the same species of organisms, one and the same genome, can exist in the guise of different living bodies. Life is a special form of coexistence of matter and information, and living bodies are products of the “materialization” of genetic information. At the protein level, genetic information is transformed into phenotypic information, where a unit of genetic information—a gene—turns into a unit of phenotypic information—a protein. Living bodies are not an end, but only a means; they are not a cause of life, but only its effect. The duality of life is part of the paradigm of duality we find inherent everywhere in our world. Other examples are matter and consciousness, matter and field, kinetic and potential energy, particle and wave, dynamic and static forces, inertial and gravitational mass, etc. In a deeper sense, duality means ambiguity. That is, if we find several levels of duality, then this also implies several levels of ambiguity in life. Despite the conventionality of our concept, from the standpoint of the duality of the phenomenon of life, we can look much more broadly at many fundamental properties of living nature. For example, it explains why individuums passionately engage in an activity that is not necessary for them to live, namely, reproduction (see Chap. 9). It becomes clear that this process is simply the maintenance of the permanent planetary system of life, in which individuums are an exclusively consumable material. This also explains the main paradox: “all organisms die, but life goes on.”

Part X

Immortality

Chapter 18

Information Constancy

18.1 Time, Space, and Life Time is one of the basic characteristics of the material world, which determines the dynamism, direction, and interconnection of processes in space. This is a form of being of matter, which characterizes the duration of existence, and the sequence and direction of changes in the states of developing material systems. This is the vector of motion of matter, the duration of motion of matter, and a measure of changes in the motion of matter. In fact, it is not even a physical, but rather a philosophical category, introduced by humans for the convenience of orientating ourselves in space. It is a measure of changes, directed exclusively from the past into the future. Space is one of the basic characteristics of the material world, which determines the length, structure, coexistence, and interaction of elements in material systems. This is also rather a philosophical category, invented by humans for the convenience of orientating ourselves relative to the localization, direction, and limits of motion of matter. Time and space are inseparable from matter, and hence from each other. In particular, in physics the spatio-temporal characteristics of material bodies and systems have four dimensions: three spatial and one temporal. Therefore, any material body exists in a specific space and time for a specific period. This property is inherent in all living bodies. The specificity of autonomous biological space and time should be noted. Biological space is the inner content of living bodies separated from the outer space by a selectively permeable dense shell. For a cell, this shell is a membrane, whereas for multicellular bodies it can be skin, wool, feathers, chitinous exoskeleton, bark, etc. The internal content of this space is absolutely astonishing compared to any place in the external environment. The totality of the internal spaces of all cells and living organisms forms a common biospace. It is estimated that the biomass of the Earth is 2420 billion tons. This means that the biospace occupies approximately 2420 billion cubic meters. On the one hand, this indicates the significance of this special space,

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but on the other hand, this volume comprises only a very small fraction of the atmospheric and terrestrial space of our planet. Figuratively speaking, it is a tiny island in the ocean. This specific biospace separated from the external environment on Earth many billions of years ago, first as an autonomous space of protobionts (see Chap. 8). With the emergence of the planetary system of life, it turned into an extensive spatial biosystem. Once it had emerged, the biospace never disappeared. It is transmitted during reproduction from one cell to another, from one organism to another. That is, the reproduction process takes place only within the context of this specific biospace. There is no emergence of new living bodies outside the biospace; the formation of a new biospace from the space of the environment never occurs. The mother cell shares with daughter cells not only the genome, but also its special habitat. The processes of variation, heredity, and evolution also take place only within this planetary biospace. That is, the phenomenon of life exists only within the context of this special biological space, which has a special content and properties (see Chap. 1). Within these boundaries, processes are carried out according to general physicochemical laws, but it may be that as yet unidentified processes are carried out according to their own peculiar laws, inherent only to the biological microcosm. Apparently, the flow of biological time also has its own specificity in the biospace of living bodies, given their complexity of structure, the tremendous rates of biochemical and biophysical processes, and the microscopic distances in cells (see Chap. 7). This specificity of bio-time has yet to be understood. Currently, based on available concepts of time, we can only note that the duration of the individual life of a living body is determined genetically and varies greatly in different biological species: from a few minutes in unicellular organisms to thousands of years in certain higher plants (see Chaps. 3–5 and 11). Each organism exists in the process for a strictly established period: it appears at a certain time, develops for a certain time, multiplies for a certain period of time, gradually grows old, lives for a strictly defined time, and then dies. All living bodies appear only once and live only one lifetime—ontogenesis. Its duration is not of fundamental importance, since it always contains birth, development, production of gametes containing an immortal genome, and transmission of the genome to future generations (see Chaps. 9–12). The duration of many metabolic and physiological processes in organisms (respiration, heartbeat, reproduction, synthetic and energy cycles in cells, etc.) is due to interactions between certain macromolecules, the presence of which is determined by genetic programs. That is, the duration and direction of metabolic processes and functions, and hence the specific lifespans of different cells and individuals of different species, is determined and regulated by the characteristics of the information of a particular genome. Thus, living bodies have, so to speak, an internal “molecular-genetic clock” of life. Obviously, the duration of existence of any living body is only an instant compared to the billions of years of existence of the phenomenon of life on Earth. For living beings, time is a vector quantity directed from the past through the present to the future.

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The vectorial nature of time is also characteristic of the planetary system of life (Fig. 18.3), which is in a mode of constant evolution. The time frame for the existence of this evolving dynamic system is determined by cosmic processes. Now, the existence of this phenomenon is due to the specific physicochemical conditions on Earth, which are associated with its special position in the Solar System. Given the finiteness of the existence of such systems, we can conclude that the time allotted to the planetary system of life and the phenomenon of life itself will also be finite. But this time frame is already determined, not by biological, but by astronomical time on a cosmic scale of billions of years. Since the Sun is gradually “cooling”, conditions similar to those on Earth could have existed several billion years ago on planets more distant from the Sun. Therefore, it is quite probable that the phenomenon of aqueous/nucleic acid/protein life in the form of a system of living bodies was already present at a certain time on other space carriers during the development of the Solar System. The changing physicochemical conditions on these carriers over hundreds of millions of years would have led to the disappearance of the manifestations of life, but the substances of life (nucleic acids, proteins, and water) may have remained to this day under the extremely cold conditions that would have prevailed. From the very moment of its inception, the unified planetary system of life has been in the process of irreversible development in astronomical time and space, in its “stream of evolution”, together with inanimate nature. This process continues every minute and second, and will continue as long as the Solar System itself exists, for approximately another 5 billion years. We are somewhere midway along the road. We are part of the global phenomenon of the planetary system of life (the aggregate system of all living beings), which is characteristic only for this moment of the endless process of the Earth’s development. It is difficult even to imagine what we will be like in a few million years. Being inside this process, being only an insignificant element within the chain of evolutionary transformations, it is very difficult for a human to understand its essence, or to determine the direction and purpose of this movement.

18.2 The Emergence and Death of Organisms Chapter 11 describes in detail the phenomenon of different lifespans of living bodies, and the causes and mechanisms of their aging and death. It is noted that the lifespans of different organisms can range from minutes to thousands of years. However, not a single organism is known to live forever. All organisms, despite their level of development, age and eventually die from external and internal causes. Prematurely, they can die from disasters, trauma, predation, hunger, and other external factors. The gradual wear of living bodies occurs naturally under the influence of constant internal thermal movement and the constant work of molecular systems, cells, and organs. For a while, organisms struggle against the increase in entropy by self-repairing at the expense of matter and energy from the external environment. Nevertheless, old organisms lose their resistance to extreme factors and can easily die due to minor

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disturbances in their homeostasis. In addition, it is absolutely certain (see Sect. 11.3) that there are genetically determined causes of aging and death characteristic of individuals of each biological species of an organism, and there are also special genetic death programs. That is, despite the inevitability of natural death, nature also forcibly genetically limits the duration of the life of each individual. Moreover, life has no means or methods to struggle against this death sentence. The immortal genome leaves no chance for any of its phenotypic frameworks to exist longer than it wants. For the death of the dwelling, the body, does not mean the death of the master, which will have migrated to another body. The life of a mammal, as the autonomous existence of a separate organism, begins (emerges) from the moment of fertilization—the fusion of parental haploid genomes. A diploid zygote is formed. This is the unicellular stage of a future complex organism. Then, the organism goes through numerous stages of development in the process of ontogenesis (see Chap. 9). The birth process is important, but only secondary, after the phenomenon of emergence of a new organism. In addition to their birthday, people should celebrate a much more significant date—the date of their emergence, nine months earlier. The essence of the above processes is the reproduction of a specific genome, and its distribution and ordered packing in a certain volume, which has the shape of a living body. Then other genetic programs are switched on (see Chaps. 11 and 12): first of all, for the maintenance of the integrity of the organism (colonies of identical genomes) and the production of gametes (the transitory form of existence of a genome). Further, the organism reproduces its own kind, grows old, and after a certain period of time, dies. The life of an individual organism ends, but the existence of its genome does not cease, if its carrier has produced offspring. That is, only the body dies, and the genome itself, the main object of life, continues to exist in subsequent generations of living bodies. In this way, the process can be repeated an infinite number of times, ensuring the longevity of the species of genomes and the immortality of the phenomenon of life. It should be emphasized that, at the moment of fertilization, life does not appear anew as a phenomenon! There is only a transfer of life by genomes from one individual to another. As a result, new living bodies appear, as fresh carriers of genomes. Then, through repeated cloning of the genome and the ordering of the phenotypic framework via differentiation, a new, complex multicellular organism appears, carrying its genome as a “baton of life”, ready to pass it on to the next generation. Consequently, individual organisms are only links in the endless chain of life of a genome. This means that it is the genome that is the main player of life, which links millions of generations of individuals into an endless chain. It should also be noted that an equally important process during reproduction is the continuous transmission of the orderliness of the cytoplasm of the dividing cell and its constituent parts to the subsequent generations. In this way, information about the organization and principles of functioning of the molecular systems of the cell is transmitted from generation to generation in a non-genetic way. With sexual reproduction, the basic organization and orderliness of the phenotypic framework of a genome does not arise anew either. They were already present in the ovum and then

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remain in the zygote. That is, in the process of continuous change of living bodies, not only the genome is copied, but so also is its habitat, in the form of the highly organized colloidal matrix of the cytoplasm. Here is another fine example of the stupendous role of the genome in the processes of emergence, life, death, and rebirth (Fig. 18.1). We have no doubt that insect larvae are living bodies, i.e., individual organisms. Yet, after pupation and metamorphosis, they disappear. Where are the dead bodies? Where do they go? Where does the life of their body go? Does their genome die during metamorphosis? Indeed, in the place of the larva, there appears a pupa, which is a completely different living body, and then there appears a butterfly, another completely different body, another organism, with completely different phenotypic traits. The fact is that the larva’s body is programmed to die during metamorphosis, disintegrating into its primary organic molecules (see Chap. 11), but the life of the genome (or, one might say, life within the genome) does not stop; it is stored in stem cells, which are then determined for the development of the pupa, and then the imago. That is, the insect genome, first at the stage of the mature larva, then at the stage of the pupa, is reprogrammed several times, disintegrating old bodies into their constituent molecules, and then using these same molecules to construct new bodies that correspond to the habitat of the next stage, without the use of matter or energy from the external environment. This example clearly illustrates the directed self-differentiation of the genome, and its primacy in relation to the bodies in which it can reside. This means that it is in the immortal genomes that the secret of life is hidden. Thus, the life of an individual organism, its entire ontogeny, is one of the stages of the process of cyclic development and a specific phenotypic manifestation of the potential of a particular genome inherent in a given biological species of organisms. The beginning of an individual’s life is associated with the beginning of the functioning (realization of potencies) of a particular genome, and the termination of life is associated with the termination of this process in a given body. Therefore, the life of an individual is a natural stage in the life cycle of a certain genome, the process of realizing its informational potential, surrounding itself with a phenotype and supporting it for its own reproduction and distribution. In turn, this genome and

Fig. 18.1 Phenotypic framework of one genome in the course of its life cycle. Zygote, caterpillar, pupa, and butterfly. The bodies of caterpillars, pupae, and butterflies die during ontogenesis, but the life of the genome is not interrupted. At each stage, the genome reprograms itself, modifies its genetic networks and controls the formation of phenomes corresponding to the future environment

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its habitat are a discrete part of the immortal planetary system of life. That is, one might say that the phenomenon of life is not due to the existence of living bodies that have genomes, but rather to the existence of genomes with a bodily framework. As noted in Sect. 11.7, the life of an individual organism is not of particular value for stable biological populations and species. Death is a genetically determined, hereditary phenomenon in the life of every organism, and is a natural, inevitable event after a certain period of time. Death is catastrophic for an individual, indifferent to its genome, but has a positive significance for species, populations, and the planetary system of life. It is the coexistence and interaction of the phenomena of emergence and death that determine the global process of exchange of living bodies and their generations, which is a necessary condition for the evolution and maintenance of the immortal planetary phenomenon of life. Paradoxically, the death of individuals is among the most important conditions for the existence of the phenomenon of life since without death there is no place for the new in the evolving planetary system. The lifespan and inevitable death of individuals is due to and unequivocally limited by genetic, thermodynamic, and stochastic causes (see Chap. 11). Individual organisms can fight them, but they absolutely cannot win (see Chap. 12). Yet, the genomes of living bodies easily get around this problem. As a result of replication and division, they continue to live without any significant changes in other, renewed bodies.

18.3 Genomic Cycles During fertilization, gametes carry hereditary information from parents to the next generation of individuals (Fig. 18.2). The genomes of heterosexual organisms merge during fertilization and form a zygote, whose genotype is a new system of interacting genes, the basis for the development of a new individual. The central role of genomes and their genetic mechanisms in the processes of reproduction and development is obvious. Even during vegetative propagation, for example, when a plant propagates by cuttings, a mass of cells containing the genome is separated off, together with part of the body. It is the reprogramming and differential expression of this separated genome that ensures the development of a new organism. And with artificial cloning, a foreign nucleus is transplanted into a denucleated egg, which serves as the receptacle for another genome. It is on the basis of the information in this foreign genome that the new organism inherent in it develops. Thus, it is obvious that, in the process of reproduction of any living body, a transorganismic transfer of genomes and genetic information is carried out, which serves as the basis for the eternity of the planetary system of life. Individual cells are a tool for transferring genomes to daughter cells. They carry out transcellular transfer of genomes, ensuring the survival and permanence of life of their species of genome. It follows from this that the main function of living organisms is production, maintenance of structural and functional integrity, and transfer of genomes to future generations (Fig. 18.2). The phenomenon of transcellular or transorganismic transfer

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Fig. 18.2 Genomic cycles or repetitive transmission of genomes through space and time by means of living bodies. 1. Replication and repetitive multiple transcellular transfer of genomes in prokaryotes by binary fission. 2. Thousand-fold transorganismic transfer of genomes in multicellular eukaryotes, which includes the processes of replication, gametogenesis, and fertilization. A—maternal organism, B—daughter organism. The period of life of a genome in a body of habitation, from inception to the next moment of reproduction, is a certain stage that can be repeated over and over again, representing a cycle where the genome is transmitted into a new phenotypic capsule

of genomes can be considered as a transition, since the genome never remains in a living body forever, but only makes a temporary stay until the next. In the nature of various living organisms, there are many diverse processes and mechanisms of reproduction, whereas the main “actor” in all this enormous variety is always the genome and the mechanism of its replication. Furthermore, the phenomenon of reproduction does not serve the reproducing individuals themselves, but only the phenomenon of life, thus ensuring its genomic immortality (see Chap. 9).

18.4 Info-Genetic Continuity Usually, when defining life, its properties, characteristics, and manifestations (nutrition, movement, reproduction, etc.) are described on the basis of observations of individual mortal representatives of the various species. In this case, life is perceived as the intermittent existence of individual bodies. However, it is obvious that the phenomenon of life is a continuous process, despite the mortality of its carriers. Thus, since genomes are the main organizing components of cells and organisms, the phenomenon of life can be considered as the process of the continuous existence of their diverse aggregate. After all, it is the genomes that travel practically unchanged through space and time for millions of years, using bodies of various shapes and sizes (various cells, organisms, gametes), which they also create. From this point of view, the various living bodies are only a habitat and a means of transit through which genomes are directed into the future (see Sect. 9.6). Cells and multicellular organisms are, so to speak, secondary, temporarily existing formations, whose main task is to create the conditions for reproduction, existence, and survival of the primary substrate of life—DNA, which constitutes the main part

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of the genome (see Chap. 17). That is, a living body is used just once by the genome for its own purposes. After a certain period, that body wears out, ages, and dies. But the “true life” in the form of the sequences of genomes continues to exist in subsequent generations of organisms through reproduction. The phenomena of latent life and anabiosis (Sect. 1.15) show that genomes can even exist under conditions unfavorable for their usual phenotypic framework. They can continue to exist without a bodily framework, but their reproduction would be impossible, for example, in ice or in an anhydrous environment. Therefore, to create conditions for their own reproduction, genomes build various bodies around themselves (or find such bodies), able to provide standard conditions for the molecular processes needed to reproduce and survive even under adverse conditions. Thus, the phenomenon of life on Earth can be imagined figuratively as a flow of different systems of genomes through different species of organisms, whose phenomes correspond to various habitats. Cell proteins are “robots” that fulfill all the “desires” of their genomic DNA. They take care of its packaging, maintain its structure, and provide for the necessary functions and the connection with the external environment. Most importantly, they provide it with a stable ecological space in the form of the contents of the nucleus and cells. This space is composed only of those molecules and their complexes required for the survival and reproduction of the genome and genetic information. In particular, the chromatin network, as well as maintaining enzymes and structures, is concentrated in a compact and highly organized manner in the nucleus. The intranuclear space of the DNA of different cells of a given organism is differentiated in diverse ways, depending on the path of development of the cell as determined by the genome. The cell cytoplasm is also a place where a number of processes that are important for the genetic apparatus occur. In particular, there is the synthesis of chromatin proteins, as well as various enzymes for transcription, replication, and repair. There is also the synthesis of purine and pyrimidine bases, formation of ATP in mitochondria, etc. Many other very different biochemical processes of anabolism and catabolism take place, whose main purpose is, in the end, to maintain order around the untouchable structure of the genome. Indirectly, through the regulation of protein synthesis, all this controls the genome itself and thus allows it to control its own environment and homeostasis. A multicellular organism is a cellular clone, since it contains hundreds and thousands of identical, but variously differentiated, sets of genomes that exist under standard stable conditions as the internal contents of a certain living body. The number of genomes corresponds to the number of nuclei of a given organism. It can reach trillions of copies, and does not always correspond to the number of cells. As already noted, a genome is first and foremost the entire set of sequences and DNA segments of the karyotype inherent in a certain species. This highly organized system includes a variety of chromosomes, chromatin proteins, a variety of enzymes, fibrils, and the ordered colloidal matrix of the karyoplasm (Chaps. 13 and 14). All these elements of the genome are combined into a single system.

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The genomes of different species of complex organism were formed during the long course of evolution as a result of transgenesis, symbiogenesis, the combination of multiple DNAs of various unicellular organisms, and the DNA of various primitive multicellular organisms, along with gene, chromosomal, and genomic mutations. Crossing, hybridization, recombination, and subsequent natural selection determined the choice and consolidation of the forms of cells and organisms. These different ways of “framing” the genomes meet several requirements: (a) they create and maintain ideal conditions for the internal environment of the genome; (b) they maximally adapt each individual’s metabolism, functions, and homeostasis to the prevailing conditions in the external space; c) they ensure suitable interaction and metabolism in the context provided by the external environment. Thus, different living bodies are above all mediators for the interaction of genomes with very diverse environmental conditions. DNA molecules in the genomic system are unique, as only these molecules can reproduce by replication (Fig. 13.1). This ensures continuous cycles of selfreproduction of DNA molecules and their ubiquitous distribution. The mechanisms of multiplication of these macromolecules also create the necessary conditions for constant self-control and self-repair, since in the course of its life DNA gets worn out due to constant operation during thousands of acts of transcription. Reproduction of DNA is also the basis for the construction of multicellular bodies and their (and hence its own) distribution. Mammalian organisms are made of trillions of cells. Since the zygote is the starting point for the appearance of all cells in an adult organism, its nucleus is the source of the formation of trillions of nuclei, each of which contains the same genome as the fertilized egg. There is a complex mechanism of mitosis, when genetic material first doubles and then is distributed to daughter cells (Chap. 9). As a result of such cloning, the nuclei of all cells in the body contain an identical genome. At the same time, over many millennia and billions of generations, there has been an amazing accuracy in the distribution of genetic material and information, with complete preservation of the structure and individuality of each chromosome in the tremendously complex cell cycle, as well as in all subsequent processes. Another mechanism of transformation and distribution of genomes is meiosis (see Sect. 9.4). This is a special type of division of genetic material of gametocytes in sexually reproducing living beings. Here, gametes form in which the chromosome set contains precisely half of the number of chromosomes of the initial cells. The genetic material in the gametes is combined in the process of fertilization, forming a diploid zygote, which contains a qualitatively new genome. Only after that is this genome rapidly cloned, building its phenotypic framing in the form of a living body. At this point, the information of the genome is maximally realized, and the genome itself is represented in trillions of copies in a multicellular body. The main task of this construction is the further production and distribution of genetic information through gametes. Reproduction of unicellular bodies is sufficient for reproduction of DNA molecules, since, after division of the mother cell, they immediately end up in different organisms. But complex multicellular organisms cannot simply divide. To

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prevent their genome from disappearing along with the old organisms, it was necessary to return to a single-celled form of existence. For this, nature created an ingenious mechanism for the reproduction of multicellular bodies through unicellular haploid gametes, a transitory form of existence of genomes (see Sect. 9.2.3). In the end, a worn-out organism is completely destroyed, broken down into separate inorganic molecules, but its genome can be preserved, and through fertilization and development, restored again to yield a new phenome of the same species of organisms. That is, the complex path of reproduction and development of multicellular organisms is a forced process that is necessary for the genome to reconstruct another “disposable body”. Hence, gametes are a forced short-term form of existence of the substrate of life, as well as a means for its survival and distribution. To illustrate the essence and mechanism of the continuous existence and spread of life, one can resort to the term reincarnation. This term is used in Eastern philosophy. It denotes the phenomenon of “transmigration of souls.” We know that the continuity of the phenomenon of life is maintained by reproduction. The cytological essence of reproduction of multicellular creatures is the formation of germ cells and their subsequent union into a zygote, and hence a new organism. Thus, during fertilization, the parental genomes “migrate” from one body to another, interacting and building the next carrier on this basis. If instead of the scientific term “genome”, we use the philosophical term “soul”, then it turns out that during the act of reproduction and subsequent fertilization, this is nothing less than the process of reincarnation, that is, the transmigration of immortal souls. Following the analogy, it can be argued that, in each of us, in each of our cells, half of our mother’s soul and half of our father’s soul continue to live. The various forms of the “phenotypic framework” of even the same genome can take on a different appearance and internal content (polymorphism) based on its differential expression. During their life cycle, such organisms can have several fundamentally different bodies with completely different phenotypes (see Chap. 18). These bodies differ significantly in size, anatomical structure, functions, habitat, reproduction, etc. This means that the same species of organism can exist in the form of different bodies! It turns out that a living body is a specific manifestation of the phenotypic framework of the genome in a certain environment and at a certain stage of development (see Sect. 17.3). This plasticity of the genome is based on its property of containing “redundant” information, as well as its ability to differentiate (see Chap. 10) and undergo selective expression (Chap. 14). Differential expression is primarily achieved through the deterministic functioning of certain genetic systems of the whole genome. This in turn is due to the special regulation of these genetic networks (Sect. 14.8). For example, mammalian genomes are quite large, but differ between each other only in 1–5% of their nucleotide sequences. However, despite the fact that the quantitative differences in the genetic material are not very significant, the phenotypes of, for instance, mice, elephants, and humans differ enormously. Dramatic differences in phenotypes can most likely be explained by the presence of different genetic programs and the formation of different genetic networks, that is, by the informational plasticity of genomes, and not by those few percent differences in their nucleotide sequences.

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It can be assumed that, on the basis of information “redundancy” and plasticity, numerous phenotypically different bodies can be reproduced from any genome. Human genetic material very likely contains potential information about the phenotypes of primates, predators, rodents, and many other evolutionarily antecedent animals. This is indicated by the biogenetic law: ontogeny recapitulates phylogeny. If, in the process of development of a human individual, all stages of the development of the animal world are repeated, from unicellular to chordates, and then to mammals, then this information must exist in some form in that individual’s genome. And this information is gradually, peculiarly applied in the process of differential expression. This is also the evidence of the info-genetic continuity of the phenomenon of life, along with the constant reincarnation of genomes. It should be noted that in the continuous dynamics of life in its various forms of manifestation, and in particular the extreme variability of the phenotypic expression of a genome, there are islands of rigorous stability in the form of practically unchanged DNA molecules and their genomic aggregates. The information that is read out, extracted from them countless times, does not change their molecular and atomic organization, although it radically changes their surroundings. This is especially evident in the development of a multicellular organism, where a highly complex ordered system is formed extremely quickly from the chaos of the surrounding space. The impetus for development is fertilization, which leads to the switching-on of specific genetic programs in the egg. After that, the material chaos of the space surrounding the genome is structured, in an intense cascade-like process, and after a certain period, part of the space is transformed into a highly organized living body, each cell of which contains a stable control system in the form of unchanging sets of DNA (see Figs. 13.2 and 14.1). Thus, the phenomenon of life is a process of continuous existence of a huge number of diverse populations of specifically organized genomes capable of using proteins to structure the surrounding material space in a directed manner. It is these immortal systems of genomes that have traveled, still travel, and will continue to travel without significant changes through space and time for billions of years, using bodies of various shapes and sizes (various cells, organisms, gametes), which they themselves create around themselves. Proceeding from the fact that the DNA of genomes are primarily the custodians and carriers of genetic information, all of the above can be extrapolated to its transformation. Then it turns out that it is information that circulates in space and time, exploiting various cells and bodies which are created on the basis of its own instructions (see Chaps. 13 and 14). The role of bioinformation is related to the direction of the flows of matter and energy into self-organizing systems with the ability to reproduce (Chap. 16). Regulation of the rates and directions of flows is carried out using special tools, viz., proteins and enzymes, as well as mechanisms, viz., methods and algorithms for their interaction with other molecules. The initial, or initiating, information is contained in the DNA of specific genomes. The realization of this information in the process of transcription is the impetus for the multiplication and cascade-like distribution of information. The next type of information carrier appears in the form of RNA,

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which has a new potential and a new information content. This in turn leads to the next round of multiplication, transformation, and dissemination of information. Here, the other carriers of information appear in the form of structural and functional proteins and enzymes, which have colossal informational potential and contain the physicochemical bases for its use in the phenotypic manifestation of traits and the appearance of structural and functional phenotypic information (Chap. 17). That is, at the protein level, the linear genetic information of nucleic acids is transformed into spatial phenotypic information. A unit of genetic information—a gene—turns into a unit of phenotypic information—a protein. This is another level of the informational potential of biosystems, causing the appearance of many variants of intracellular structures, and an infinite variety of cells and multicellular organisms. Thus, both genetic and phenotypic information is of strategic importance in realizing living bodies through multi-stage processes of expression, synthesis, and organization. The aggregate of information from discrete genomes of all living bodies forms the unified information space of the phenomenon of life (the genosphere) (Chap. 17). Within this space, a constant circulation of biological information is maintained. This circulation inevitably goes through specific organisms (the phenosphere) and their genomes, which are the instruments for operating with matter, energy, and information. Within the genosphere, information circulates at the level of replication, transcription, transgenesis, hybridization, and recombination, whereas, within the phenosphere, material and information flows are represented by a continuous discontinuity of diverse cells and living bodies, the phenotypic manifestations of information in genomes. The phenomenon of life has been continuous for several billion years. Its infiniteness lies in its dual nature. Despite the fact that the material component of living bodies wears out and dies, the non-material substrate of life in the form of information is not subject to aging and death. During reproduction, information is recreated anew by replication and, together with the genome, passes from one body to another, causing the revival and continuity of life. Mortal living bodies are only a means of maintaining the continuous process of life on Earth. Individuals serve only as a means of survival and reproduction for genomes, and the purpose of reproduction and evolution is not the survival of organisms, but the survival of genomes and the biological information they carry. Cyclic reproduction of genomes and their continuation in the offspring is a prerequisite for the endless process of the phenomenon of life. This is an important property of living bodies, although it does not serve those bodies, but rather the planetary system of life. The eternal existence of the planetary system of life is due precisely to the exchange of living bodies in the form of inevitable death and continuous reproduction of the elements of the system. It is the genome, through the differential expression of genetic information, that carries out reproduction, development, and nearly all biological processes. The processes of variation, heredity and evolution of the planetary system of life take place on the basis of the reproduction of organisms and natural selection. Consequently, the integral vector of life consists of an infinite set of life cycles of reproduction of the entire set of genomes (Fig. 18.3). Given what has been said and the fact that information is continuously transmitted with the

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Fig. 18.3 Integral vector of the life process. 1- The vector representing the phenomenon of life is linear and infinite under the present conditions. It is not known where it began and where it is headed. 2—The vector representing the lives of living bodies is cyclic, short, and finite. It starts from one maternal organism and is directed to another maternal organism through the reproduction of genomes. 3—The integral vector of the planetary system of life consists of an infinite set of life cycles of living bodies. This is an integral phenomenon determined by the existence of an enormous number of different living bodies that reproduce a myriad of genomes

genetic material, we can talk about the info-genetic continuity and “immortality” of the phenomenon of life. Thus, the information-genetic continuity of life on Earth manifests itself in the form of a continuous process of existence of a global system of constantly reproducing and evolving genomes in various forms of their bodily framework.

Chapter 19

Conclusion: Dictatorship of the Genome

Based on the facts stated in the book, we can reasonably conclude that living bodies are the habitat of genomes, where they are localized and reproduce. Through the bodies they inhabit, genomes are in contact with the external environment, receiving matter, energy, and information. This ensures their homeostasis and replication. That is, living bodies are not the main objects of life, but only its temporary holders and carriers. They are not the content, but only a form; not the cause, but only an effect. Thus, taking into account the data presented in the previous chapters, the following generalizations can be made about the determining role of the genome in all aspects of the activity of living systems: 1.

2.

3.

4.

All biological species of the planetary system of life consist of individuals with a limited lifespan. However, the continuity of the existence of life is determined by the ability of the genomes of individuals to reproduce, which ensures the long existence (millions of years) of a given species of living organism, or rather, a given species of genome. The genome is not only a collection of genetic information, but also the key macrocomponent of the cell that contains a corresponding set of nucleic acids and proteins, united into a single complex structural and functional system. This system contains a full range of special information, but also a special structural organization, along with the tools and mechanisms for its implementation and use. Multicellular organisms can have different cells, tissues, and bodies, inhabit all kinds of environments, have different metabolism and functions, but at the same time be derivatives of the same genome. Moreover, all forms of bodies are absolutely functionally equivalent for a particular species of genome, since in any case they serve only for its adaptation to a certain habitat. Therefore, it is not entirely correct to speak about the existence of a given biological species of organism, but it is better to assert the existence of a given species of genome, which can exist in different forms of phenotypic framework. Any multicellular organism consists of a large number of cells that differ in structure and function. The lifespan of almost all cells is shorter than the lifespan

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7.

8.

9.

10. 11.

12.

13.

14.

15.

19 Conclusion: Dictatorship of the Genome

of the whole organism. Only the constant renewal of cells, supported by the expression and reproduction of genomes, can ensure the long-term existence of multicellular individuals. The life of an individual organism is one stage in the process of cyclical development and a specific phenotypic manifestation of the potential of a particular genome inherent in a given species. The beginning of an individual’s life is associated with the beginning of the realization of the potentials of a particular genome, and the termination of life with the termination of this process in a given body. The processes of reproduction of genomes determine and support the phenomenon of the exchange of living bodies and the change of generations in the populations and species of the planetary system of life. The reproduction and replication of genomes are the basis of genetic variation and adaptation of taxa. This property of genomes is also the basis of evolution and the cause of the immense diversity of living organisms. Natural selection conditions the fixation of species of genomes and phenomes that survive and adapt well to their habitat. Living bodies are mortal, and it is only their genomes that actually multiply and travel through time and space, ensuring the immortality of the phenomenon of life. The genome is not subject to death. Millions of genomes travel over tens of millions of years from one mortal body to another, ensuring the constancy and gradual evolution of their species, and the permanence of the planetary system of life. Genomes are the element of life that constantly survives in the struggle against inevitable entropy. Periodic rewriting and editing of genetic information during each cycle of reproduction creates conditions for strict control of the integrity of the genome. Within the vast diversity of different living organisms, there are many mechanisms of reproduction. However, the main “actor” in all the myriad variants is always the genome. There is experimental evidence indicating the possibility of autonomous, purposeful self-modifications of genomes. That is, the genome is an active self-regulating and self-organizing system that has the ability to purposefully create new genotypes and phenotypes to actively participate in the process of its own evolution and survival. Parthenogenesis indicates the ability of the genome to autonomously motivate reproduction and survival. Even if an individual of the opposite sex is available, the haploid genome of an egg can independently decide on its own reproduction. The genome has the unique ability to manipulate information by manipulating molecules, and by manipulating information to manipulate substances, energy, and living bodies. In other words, the genome, by operating with matter, operates with information, and by operating with information, operates with matter. The ability of the genomes of living bodies to independently generate and use information (bioinfogenesis and infobiogenesis) is the basis on which the planetary system of life exists and evolves.

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16. The genome of eukaryotes is a dynamic self-regulating structure that can exist in different forms of ploidy. Within the life cycles of mortal organisms, it is the genome that has a permanent cyclic transformation. It periodically switches from a haploid form of existence to a diploid one, differentiates, and, building another habitat around itself, the body, ensures its own immortality. 17. For multicellular organisms, both monoecy (hermaphroditism) and dioecy (the presence of female and male organisms) are characteristic. That is, the genome can equally well be located in one body and produce two types of gametes, or be located in two, each of which produces one type of gamete. It can also be accommodated in more types of body, as in the case of bees, where there is a queen, drones, and workers. Obviously, the division of individuals by sex or social purpose is not decisive in the existence and reproduction of the genome; it is merely a consequence of its ability to adapt through a variety of phenotypic frameworks. 18. The phenomenon of polymorphism, which is the formation of different cells and living bodies from one genome, can be referred to as the property of polyphenotypic genomes. This is due to the genome’s ability to be differently determined, differentiated, reprogrammed, and expressed, depending on the stage of development and intended environmental conditions. Moreover, this does not depend on the karyotype, i.e., on the genic and allelic composition of the genome, as they remain unchanged in all cases. 19. The dominant role of the genome, which can do whatever it wants with its phenomes, is also evidenced by the amazing phenomenon of sex change in some organisms during the life of an individual (for example, in some fish). At the same time, the genome, without changing, but only switching the genetic program, continues to pursue its main goal—to survive and reproduce. 20. The totality of information in the genomes of all living bodies constitutes the genosphere, which is the basis for the permanent existence of the phenosphere. Being interdependent and conditioning each other, the totality of genomes and phenomes forms a single planetary system of life. The strategic goal of such an organization is the complementarity of the genome system with respect to a diverse material environment through a system of qualitatively different phenotypes. 21. The genome is primary. Cells are the first derivatives of the genome. Multicellular bodies are the second derivatives of the genome. The planetary system of life is the third derivative of genomes. The phenomenon of life is the fourth derivative of genomes. All in all, the life of an individual is a natural stage in the life cycle of a certain genome, the process of realization of its informational potential by surrounding the itself with a phenotype and ensuring its own reproduction and distribution. In turn, this genome and its body are a discrete part of the immortal planetary system of life. That is, the phenomenon of life is not due to the existence of living bodies that contain genomes, but rather to the existence of genomes with bodily frameworks.

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Thus, our planet is inhabited by diverse species of genomes that build bodies around themselves, which correspond to all kinds of habitats, and use those bodies for their own purposes. It is obvious that the genome is the dominant part of the discrete and widely diverse phenomenon of life. Its power and authority extend to individual cells, and to individual organisms, and to biological species, and to the planetary system as a whole. ∗ ∗ ∗ Once again, we note that our book is not a strictly scientific work, although it is based on scientific concepts and the laws of Nature. Rather, it is a scientificphilosophical work, containing reflections “on the nature of things.” Philosophy is the key to understanding and generalizing seemingly incompatible things and concepts; it is an unconventional view of obvious notions, and it is the basis for the emergence of fundamentally new hypotheses and ideas. We live in a world of conventions and illusions that we have built. Only a philosophical approach to understanding the reality we perceive can temporarily satisfy our desire to explain and connect everything into a single picture of the world and make up for our powerlessness to realize the essence of the endless movement of an unattainable entity.

Glossary

For a better understanding and perception of the ideas presented here, several key concepts used in the book should be introduced. 1.

2.

3.

4.

5.

Life or the Phenomenon of Life. Life as a global phenomenon of nature consists of two complementary components. On the one hand, life is connected with the process of existence of autonomous living bodies with individual life. On the other hand, life exists in the form of a planetary system of life, consisting of an infinite number of such bodies. That is, the phenomenon of the planetary system of life differs from the phenomenon of the existence of autonomous living bodies, despite the inextricable link between them. We perceive the monolithic interdependent coexistence of the living bodies and the planetary system of life as a global phenomenon of life. Planetary System of Life. This is the complex of all living bodies on Earth. It is the integral whole of the lives of interdependent and interacting organisms. It is the sum of all mutually integrated functioning genomes that form the genosphere, including the phenomes, that form the phenosphere. Phenosphere or Global Phenome System. This is the material component of the planetary system of life. It is the totality of all functioning and interacting living bodies. Within this nominal system, discrete organisms are unified by their common proteinic nature. Genosphere or Global Genome System. This is the informational component of the planetary system of life. It is the totality of all functioning and interacting genomes of all living bodies on the planet. Within this system, discrete genomes are unified by the singular nature of nucleic acids and the encoding of genetic information, forming an integral informational field of life. The expression of information from individual discrete genomes produces specific manifestations in the form of living bodies, which in turn constitute the phenosphere. Living Bodies. Physical objects that have biological properties and characteristics. They are autonomous discrete units of the phenomenon of life. Living bodies are temporary dissipative self-recovering systems capable of reproduction. Living bodies are possessors and carriers of individual life.

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6.

Glossary

Life of a Body or Individual Life. A dynamic process of the limited existence of individual units of life from the moment of appearance to death. Individual life is based on the course of a combination of physicochemical and biological processes aimed at maintaining its own vital activity. It is passed from ancestors to descendants from generation to generation through the reproduction of their immortal genome. 7. Death of a Body or Individual Death. The moment of irreversible cessation of the main processes and functions that support the life of a body. Death is a hereditary phenomenon in the life of every organism and is a natural, inevitable event after a certain period of time. Death is tragic for an individual, indifferent to its genome, but has a positive meaning for species, populations, and the planetary system of life. Birth and death determine the global process of exchange of living bodies, which is a necessary condition for maintaining the immortal planetary phenomenon of life. 8. Immortality. The hypothetical possibility of the endless existence of a living system. 9. Genes. Units of genetic information that control the occurrence of all traits. They are DNA regions that perform specific functions: encode RNA and proteins, upregulate or downregulate the action of other genes, participate in the relocation of nucleotide sequences, and so on. Genes are the main informational and functional units of the genome. 10. Genome. A structural complex of a cell, which contains a specialized set of nucleic acids and proteins that are organized as a unified structural and functional system. This system contains the genetic material and information necessary for the generation, functioning, and reproduction of a given type of cell or organism, but also includes physical mechanisms and instruments for the implementation of this information. It includes a set of special structures and dozens of enzymes, as well as regulatory and structural proteins. The genome is an integral entity capable of manipulating matter and information, reproducing, and building a phenotypic framework around itself. Genomes use their phenotypic framework to interact with other genomes and with the environment. The genome of a biological species is the standard genome belonging to each organism of a given species as an individual genome. It contains a specific set of genes and algorithms for their expression, leading to the formation of a particular phenome. 11. Phenome. The structural complex of a cell, composed of various elements of the cytoplasm and the surface apparatus. It is a sophisticated system of the phenotypic framework of the genome. This is the part of a cell that surrounds the genome and integrates it into itself, forming a monolithic body with it. The phenome of a multicellular organism is composed of an organized mass of differentiated cells and intercellular substance, along with a set of metabolic and physiological processes of the organism which oppose environmental factors, sustaining homeostasis in the body and maintaining the aggregate genome. The phenome of a biological species is a standard set of morphological, physiological, biochemical, and ecological characteristics inherent in that species.

Glossary

429

12. Proteome. The complex of all proteins in a living body. It is also a material and informational link between the genome and the phenome, which, by means of protein interactions, form an integral living body: genome → proteome → phenome. 13. Cell. The unit of structure and function of the whole multitude of living organisms. It is the primordial element of individual life. This is a pattern of organization of living organisms, a microscopic living body, consisting of two integrated interlocking systems: the genome—the administrative system of life, and the phenome—the executive system of life.

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