In Search of Cell History: The Evolution of Life's Building Blocks

By Franklin M. Harold

This comprehensive history of cell evolution “deftly discusses the definition of life” as well as cellular organization, classification and more (San Francisco Book Review).
 
The origin of cells remains one of the most fundamental mysteries in biology, one that has spawned a large body of research and debate over the past two decades. With In Search of Cell History, Franklin M. Harold offers a comprehensive, impartial take on that research and the controversies that keep the field in turmoil.

Written in accessible language and complemented by a glossary for easy reference, this book examines the relationship between cells and genes; the central role of bioenergetics in the origin of life; the status of the universal tree of life with its three stems and viral outliers; and the controversies surrounding the last universal common ancestor. Harold also discusses the evolution of cellular organization, the origin of complex cells, and the incorporation of symbiotic organelles. In Search of Cell History shows us just how far we have come in understanding cell evolution—and the evolution of life in general—and how far we still have to go.
 
“Wonderful…A loving distillation of connections within the incredible diversity of life in the biosphere, framing one of biology’s most important remaining questions: how did life begin?”—Nature

• Language: English
• Publisher: Open Road Integrated Media
• Release date: Oct 29, 2014
• ISBN: 9780226174310

Book preview

Franklin M. Harold is professor emeritus of biochemistry at Colorado State University and affiliate professor of microbiology at the University of Washington.

The University of Chicago Press, Chicago 60637

The University of Chicago Press, Ltd., London

© 2014 by The University of Chicago

All rights reserved. Published 2014.

Printed in the United States of America

23 22 21 20 19 18 17 16 15 14      1 2 3 4 5

ISBN-13: 978-0-226-17414-3 (cloth)

ISBN-13: 978-0-226-17428-0 (paper)

ISBN-13: 978-0-226-17431-0 (e-book)

DOI: 10.7208/chicago/9780226174310.001.0001

Library of Congress Cataloging-in-Publication Data

Harold, Franklin M., author.

In search of cell history : the evolution of life’s building blocks / Franklin M. Harold

pages cm

Includes bibliographical references and index.

ISBN 978-0-226-17414-3 (cloth : alkaline paper)—ISBN 978-0-226-17428-0 (paperback : alkaline paper)—ISBN 978-0-226-17431-0 (e-book)

1. Cells—Evolution—Popular works.   2. Cytology—Popular works.   3. Life (Biology)—Popular works   I. Title.

QH582.4.H37 2014

571.6—dc23

2014006515

This paper meets the requirements of ANSI/NISO Z39.48–1992 (Permanence of Paper).

In Search of Cell History

The Evolution of Life’s Building Blocks

FRANKLIN M. HAROLD

THE UNIVERSITY OF CHICAGO PRESS

CHICAGO AND LONDON

TO ALL SCIENTISTS WHO WALK IN THE PATH DARWIN FIRST BLAZED, SEEKING A RATIONAL ACCOUNT OF THE NATURE AND ORIGIN OF LIVING ORGANISMS, AND TO THOSE WHO WILL COME AFTER US

Contents

Preface

Acknowledgments

CHAPTER 1. Cells, Genes, and Evolution: On the Nature and Workings of Life

CHAPTER 2. The Tree of Life: Universal Phylogeny and Its Discontents

CHAPTER 3. A World Mostly Made Up of Microbes: Bacteria, Archaea, and Eukarya

CHAPTER 4. The Deep Roots of Cellular Life: The Common Ancestry of Living Things

CHAPTER 5. The Perplexing Chronicles of Bioenergetics: Making a Living, Now and in the Past

CHAPTER 6. Life’s Devices: On the Evolution of Prokaryotic Cells and Their Parts

CHAPTER 7. Emergence of the Eukaryotes: The Second Mystery in Cell Evolution

CHAPTER 8. Symbionts into Organelles: Mitochondria, Plastids, and Their Kin

CHAPTER 9. Reading the Rocks: What We Can Infer from Geology

CHAPTER 10. Ultimate Riddle: Origin of Cellular Life

CHAPTER 11. The Crooked Paths of Cell Evolution: Cell Evolution Is Special

CHAPTER 12. Summing Up: Journey without Maps

Notes

Glossary

References

Index

Preface

Biology presents us with innumerable puzzles and also a handful of mysteries, questions that point beyond the conceptual framework of our own day. None is more fraught than the genesis of life, that unique state of matter in which the dust of the universe attains complexity, autonomy, purpose, and the capacity to reflect on its own nature. How living things came to be is arguably the most momentous issue in biology today; the object of this book is to consider how far we have come in the quest for rational understanding of our deepest roots.

Life is so familiar and ubiquitous that it is easy to forget how astonishing it is, and how sharply living things differ from those that are not alive. Living things draw matter and energy to themselves, maintain their identity, reproduce their own kind and evolve over time. Nothing else in the known universe has this capacity. Living things are made up of lifeless chemicals; their composition, and everything they do, is consistent with the laws of physics and chemistry. And yet there is nothing in those laws that would lead one to expect a universe that harbors life. At the heart of the mystery lurk cells, the elementary units of life and the smallest entities that display all its characteristics. Every living thing is made up of cells, either one cell or many, and every cell is itself a highly integrated ensemble of millions of molecules structured in space. Truly, the cell is the microcosm of life, and in its origin, nature and continuity resides the entire problem of biology.¹ When we inquire into the genesis of life, the primary objective must be to understand the origin of cells and of cellular organization.

The history of life unfolds over a time span so vast it boggles the imagination. I, for one, can draw no meaning from a million years, let alone a billion, and prefer a geographical metric. Let 1 millimeter, the thickness of a dime, stand for 1 year. Then 1 meter makes a millennium, 1 kilometer 1 million years, and the age of the earth (about 4.5 billion years) spans 4,500 kilometers, a little more than the distance between Miami and Seattle. As you fly northwest across the United States, armed with the latest in spyware, you may spot the first signs of life over Tennessee. Unmistakable bacterial cells appear over Kansas, eukaryotic ones over Nebraska. Western Montana features the Cambrian explosion, mammals make their debut near Spokane; and the plane is preparing to land before the first hominids rise up on 2 feet, just 4 or 5 kilometers short of SeaTac Airport. That huge span of time between Memphis and Missoula, 3,400 to 600 million years ago, is the era of cell evolution; and it remains today as thinly charted as the West was when Lewis and Clark set out on their Voyage of Discovery.

The evolution of life as displayed in museums of natural history turns on forms and functions whose scale matches our own: skulls, wings and fins, leaf imprints, ammonites and the puzzling creatures of the Burgess Shale. But all these are latecomers. For more than three-quarters of life’s history, all the life that lived consisted of single-celled microorganisms invisible to the naked eye. By the time multicellular organisms appear in the geological record some six hundred million years ago, the evolution of cells themselves had largely run its course. To be sure, cell evolution continues even today, with the proliferation and diversification of bacteria and protists and the elaboration of the specialized cells of animals and plants. But the core of the subject is the genesis of the basic cell types, and their spatial and functional organization. Everything we know suggests that between Memphis and Missoula, cells arose from the primordial slime; acquired the familiar complement of parts and functions including ribosomes, cell walls, flagella, protein synthesis, and photosynthesis; and generated the molecules that make up those structures and underpin their operations. Cell evolution is, first and foremost, about how cells came to be; and as we pursue this inquiry, we are bound to achieve better insight into the nature of life itself.

The genesis of cell organization is a historical subject, for which the sources of information are quite limited. In principle, the most direct is the testimony of the rocks. Fossils have been invaluable in tracing the evolution of animals and plants, but are much less enlightening about unicellular microbes. Even so, geology supplies a chronological framework, a window onto the environments in which life first took hold, and an invaluable corrective to exuberant speculation. Synthetic biology, the ongoing effort to construct living cells in the laboratory, may in the future offer useful insights but has thus far generated more heat and smoke than light. The most productive mine of information by far has been the biology of living organisms, genomics in particular. In the 1960s it was first realized that the sequences of proteins and nucleic acids hold a record of the evolution of those molecules, and by implication of the organisms that house them. Forty years on, we are well lost in that Library of Babel: We have now come to rely on gene phylogenies to recreate evolution’s pattern, and to see genomes as surrogates for organisms, as well as chroniclers of the process of evolution: we have reduced evolution to (phylo)genetics and genomics.² Anyone who reflects on evolution must draw heavily on genomic data, and so will I. But the interpretation of the genomic record is anything but straightforward, and very few inferences enjoy general assent. Besides, it turned out that the history of cells is not identical with the history of their genes, and there is reason to believe that not all the information that specifies cellular architecture is carried in the genome. In the end there is no safety in sequences, or anywhere else.

Cell evolution is a quirky subject, out on the margins of serious science. The traces of events that occurred in the remote past are commonly faint and ambiguous. Interpretations rely heavily on extrapolation and conjecture; opinions are passionately held, but rest as much on conviction and rhetoric as on objective facts. The standard method of science, the formulation and testing of falsifiable hypotheses, can seldom be applied. But those who love science for its big questions and windy spaces find the lure of cell evolution irresistible: here, more than anywhere else, we touch the outermost limits of what we know, perhaps the limits of what we can know.

This book is a sequel to my previous one, The Way of the Cell,³ which sought an answer to the question most famously posed by the physicist Erwin Schrödinger, What is Life? That book touched on many evolutionary matters, but it was not until I began to compose its successor that I realized just how explosively the literature has grown over the past decade. I have tried to ground the present volume squarely in the current literature; my object is not to promote my own interpretations (which continue to evolve) but to render a fair and comprehensible account of the ideas and controversies that keep the field in turmoil. This has entailed many personal choices among competing claims, which explains the frequent appearance of the first-person singular in these pages. To hold the length within reason, it was necessary to assume that the reader has a basic knowledge of cellular and molecular biology, but I have made every effort to keep the text accessible and technicalities to a minimum. Readers who wish to delve deeper will find numerous portals among the references, largely selected from publications over the past decade; responses to the literature extend through 2012.

I came to cell evolution through the back door by way of a long engagement with the spatial organization of biochemical processes, first in bacterial energy transduction and later in cellular morphogenesis. For that reason I look on cell evolution from the perspective of a physiologist, as the progressive emergence of spatially ordered systems of molecules that possess the extraordinary capacity to make themselves. This book was written in the belief that one can learn something about biological organization from the history of cells, and come to better understand cell history by examining it through the prism of organization. Inevitably, many matters discussed in this book fall outside the range of my professional expertise. This is a familiar predicament that confronts anyone who would write of science for a wider audience; and so I take comfort from the apologia of Thomas Sprat, who set out to write a history of the Royal Society of London three hundred years ago.

Perhaps this task which I have propos’d to my self will incur the censure of many judicious men, who may think it an over-hasty and presumptuous attempt . . . Although I come to the performance of this work with much less Deliberation and Ability than the Weightiness of it requires; yet, I trust, that the Greatness of the Design itself, on which I am to speak . . . will serve to make something for my Excuse.⁴

Acknowledgments

The object of science is to make sense of the world, but our immediate product is commonly information, reams and reams of it, far more than any one person can assimilate. So I am indebted first and foremost to the scholars of science, those who set in order the raw output of research in the form of reviews and commentaries. This book could never have been written without them. Many such contributions are cited in the text, but formal acknowledgment fails to do justice to mentors, colleagues, and friends, past and present, who sharpened my understanding of evolution through their writings or by instruction, correspondence, and conversation. Ford Doolittle, Stephen Jay Gould, Arthur Koch, Nick Lane, Lynn Margulis, William Martin, Daniel McShea, Peter Mitchell, Harold Morowitz, Norman Pace, Moselio Schaechter and Roger Stanier, thank you all. The alphabet dictates that Carl Woese come last on this list, but in my debt he ranks first, for it is his vision of cell evolution that set the course for this journey. Special thanks are also due to Loren Eiseley—naturalist, philosopher, and poet—who taught me at a critical juncture that the true use of science is to make the world intelligible and renewed my commitment to my profession.

Colleagues and friends in Seattle and elsewhere reviewed portions of this book during its gestation. John Leigh and Moselio Schaechter commented on individual chapters; Eric Fourmentin, Ruth Harold, Nick Lane, Daniel McShea, Diana Sheiness, and James Staley loyally stayed the entire course. They, as well as two anonymous reviewers, spotted more ambiguities, misstatements, omissions, and outright errors than I care to admit; and I have corrected those as best I could. In the end, the opinions and attitudes expressed here are my own and no one else should be held responsible.

I write by hand, and so I am much indebted to Jennifer Chubb for turning stacks of scribbled yellow paper into neat typescript. Thanks are due also to colleagues who allowed me to adapt diagrams from their work or supplied original photomicrographs, and to the journals in which those contributions were first published. Kate Sweeney, medical and scientific illustrator at the University of Washington, and artists at Visual Health Solutions in Fort Collins, Colorado, drew the illustrations. I am doubly grateful to Jennifer Chubb, Diana Sheiness, and to my ever-helpful editor Christopher Chung for keeping this project on track when I was sidelined by illness while preparing the manuscript for publication.

Finally my thoughts turn to my wife Ruth, who aided and abetted this project from the beginning and cheerfully put up with an oft-distracted husband. In the lab, wandering the globe, and throughout life’s journey, I could not have wished for better company.

CHAPTER ONE

Cells, Genes, and Evolution

On the Nature and Workings of Life

Men talk much of matter and energy, of the struggle for existence that molds the shape of life. These things exist, it is true; but more delicate, elusive, quicker than the fins in water, is that mysterious principle known as organization, which leaves all other mysteries concerned with life stale and insignificant by comparison. For that without organization life does not persist is obvious. Yet this organization itself is not strictly the product of life, nor of selection.—Loren Eiseley, The Immense Journey

The Doctrine of the Cell

Microbes Come on Stage

Prokaryotes and Eukaryotes

Molecular Systems of Daunting Complexity

Genes Rule

Cell Heredity

Cell Evolution: What Nobody Is Sure About

Unlike most husbands, I quite enjoy doing the dishes; it seems to satisfy a need to impose order on my corner of the world, at least for a little while. I begin with the sink piled helter-skelter with soiled plates, cups, and cutlery; twenty minutes later all are clean and neatly ranged in the rack, the large ones in the rear and the small ones in front. I look upon my work and see that it is good, and I have no doubt that the same need to find order in the universe motivates much of science.

Biologists encounter the tension between order and randomness every day, for living things differ from nonliving ones most strikingly in their degree of order. When used in its technical sense, the term order refers to regularity, predictability, and conformance to law. Wallpaper is ordered, repeating a particular pattern over and again. The deep blue bird that occasionally visits my garden is called a Steller’s jay. It furnishes a spectacular example of order, for that label immediately implies a host of regular and predictable features: forms and colors, a set of anatomical and biochemical characteristics, even a pattern of behavior. Regularity and predictability are also found in the nonliving world (the solar system comes to mind), but not to the same degree. Besides, the order that living things display is of a special kind, commonly termed organization: that jay’s patterns of order have purpose or function. This feature is seen only in living things and their artifacts, such as airplanes, spider webs, or the shells constructed by testate amoebas. Nevertheless, their intricate organization notwithstanding, living things are creatures of contingency. They are not manifestations of physical laws as the solar system is, nor were they designed for a purpose like the airplane, but rather they evolved by the interplay of random variation and natural selection. Living things conform to the laws of physics and chemistry but are not fully explained by those laws; and their existence could not be deduced from physics and chemistry. Despite their familiarity and ubiquity, living things are truly strange objects.

The Doctrine of the Cell

One of the earliest and most profound statements about biological organization is the cell theory, rightly acclaimed in every textbook as a cornerstone of biological science. The theory asserts that all the infinite diversity of living things is constructed on a single architectural plan: every organism is made up of cells, consisting either of a single cell or of a society of many cells. Cells are the atoms of life, and life is what cells do.

The idea of the cell emerged gradually over a period of two centuries.¹ Robert Hooke coined the term in 1665, when he examined thin slices of cork through a microscope and saw a pattern of rectangular boxes that reminded him of monks’ cells (we now know that he was not looking at cells in the modern sense, but at their empty rigid walls). As microscopes grew sharper and more powerful others reported similar patterns, and the suspicion grew that cells might be a general feature of living things. It fell to a pair of German scientists, the botanist Matthias Schleiden and the physiologist Theodor Schwann, to articulate the consensus that was waiting to be born (1838 and 1839). Their cell doctrine stated that the tissues of plants and animals were not homogenous wholes, but rather composed of innumerable tiny individual cells. Each cell consists of a droplet of jelly, later called protoplasm, enclosing a dense central kernel, or nucleus. And they explicitly recognized that each cell is itself a complex and organized structure and the seat of the organism’s vital activities.

Two decades later the prominent pathologist and physician Rudolf Virchow took the next step. Schleiden held the position that cells formed by aggregation of protoplasm around the nucleus. Virchow knew better: in his textbook of pathology, published in 1858, he insisted that every cell originates by division from a pre-existing cell. His famous aphorism, Omnis cellula e cellula (every cell from a previous cell) remains another landmark of biological science. Cellular organization has passed continuously from the dawn of life to the present day. Organization is sometimes transmitted by division, sometimes by the fusion of gametes, but it never arises de novo. With the rise of molecular science, Virchow’s law has been marginalized, but it continues to hold and is central to the present book.

Microbes Come on Stage

The pioneers of the cell doctrine thought entirely in terms of higher organisms, the multicellular animals and plants; of the microbial world the early nineteenth century knew very little. Microscopic organisms had been seen and described by Anton van Leeuwenhoek (1632—1723), merchant and civic official of Delft in Holland and a lens grinder of extraordinary skill. With the aid of what was, in effect, a powerful magnifying glass, Leeuwenhoek observed spermatozoa and red blood cells, capillary vessels, all the major kinds of algae, protozoa, and yeast, and even some bacteria. He reported his discoveries in a stream of letters (in Dutch) addressed to England’s Royal Society, which duly translated and published them. But the pace of discovery slackened after Leeuwenhoek’s death, largely for technical reasons, and quickened only with the advent of more advanced microscopes.

The novel and sometimes peculiar creatures thus revealed posed problems for biologists, whose interests centered on taxonomy. Scientific tradition reaching clear back to Aristotle recognized two kingdoms of living organisms, animals and plants. Some of the microorganisms could be shoe-horned into one or the other kingdom, but that procedure grew increasingly unsatisfactory as microscopists discovered tiny organisms that were neither plants nor animals yet had qualities of both; the alga Euglena, for example, which is both green and motile. There was much argument over whether such organisms should be considered unicellular or noncellular, but the instruments that revealed the internal structure of protozoa and algae also documented their essential affinity with the cells of higher organisms. In 1866, Ernst Haeckel, Darwin’s champion in Germany and one of the most prominent scientists of his day, published a universal classification with three, rather than two, major categories: animals, plants and protists. His kingdom Protista included a grab bag of lower creatures: the protozoa, unicellular green algae, fungi, diatoms, and much else besides, including the bacteria. The latter were set apart in a subgroup of their own, the Monera. Among the protists, Haeckel was convinced, would be found not only the ancestors of plants and animals, but also descendants of the primordial organisms with which life began.

The bacteria never nested comfortably among the other protists. The cells of protozoa, algae, and also fungi were organized along the same lines as those of plants and animals, with a nucleus that divides by mitosis, a bounding membrane and various internal organelles and inclusions. Bacterial cells were much smaller and lacked a nucleus, they did not divide by mitosis, and even seemed to do without heredity. As early as 1938, a formal proposal was made to remove bacteria from the protistan realm and assign them a kingdom of their own. Bacteria were clearly fundamentally unlike other cells, but the nature of the difference remained undefined for another quarter of a century.

Prokaryotes and Eukaryotes

By the middle of the twentieth century, microbiology was becoming a hotbed of intense research. Bacteria had been well recognized as a large and diverse group of organisms, the agents of human diseases and industrial processes as well as the grand nutrient cycles, and probably the oldest forms of life. Moreover, thanks to their small size and relatively simple organization, bacteria had become the beacon that would illuminate all of cell physiology, biochemistry and genetics. Escherichia coli reigned as everyone’s favorite model organism. Yet those microbiologists whose interests ran toward natural history often felt frustrated by their inability to achieve an objective classification of the bacteria, or even to define the relationship of bacteria to the rest of the living world.

The question of the essential nature of bacteria was tackled by two of the most respected microbiologists of the time, Roger Stanier (1916–1982) and C. B. van Niel (1897–1985), in a magisterial paper entitled The Concept of a Bacterium (1962)² By then, thanks chiefly to the perfection of the electron microscope, enough had been learned about the ultrastructure of bacteria to differentiate them unambiguously from other kinds of cells. Stanier himself was especially influenced by his mounting interest in the cyanobacteria, photosynthetic organisms familiar to everyone as the green scum that forms on the surface of stagnant ponds. The blue-green algae were traditionally considered to be simple plants and studied by botanists; yet their fine structure clearly ranked them with the bacteria and demanded that they be reclassified. To give substance to the concept of bacteria as a separate, kingdom-level class of organisms, Stanier and Van Niel adopted and promoted terminology that had been mooted by the French protozoologist Édouard Chatton thirty years before: eukaryotes and prokaryotes, cells endowed with a true nucleus and cells without.

The tale of how this fundamental distinction came to be naturalized in biology is curious, and illuminates how science actually works. Several generations of students have been taught to credit Chatton with its discovery. But when the historian Jan Sapp reexamined the matter,³ he found that Chatton himself had made little of the distinction between prokaryotes and eukaryotes; to him these were just convenient labels, not an insight into the nature of things. It was really Stanier and Van Niel who drew the bright line across biology, separating two modes of biological organization.

The cells of plants and animals, including our own, display the eukaryotic mode. The same is true of fungi and of protists (fig. 1.1). All possess a membrane-bound nucleus that contains chromosomes and divides by mitosis. They contain organelles such as mitochondria, golgi, and (in photosynthetic organisms) plastids. An intricate system of internal membranes pervades the cytoplasm, and a cytoskeleton can often be made out. They also have cilia and flagella, organs of motility built around microtubules (I like Lynn Margulis’s term undulipodia to designate these structures and shall use it hereafter). Prokaryotic cells are much smaller and simpler in structure. They lack a nuclear membrane, chromosomes, and mitosis; there are no organelles and (usually) no internal membranes. Their flagella differ from undulipodia in structure and operation, and their cell walls are chemically different from those of eukaryotes. Stanier and Van Niel defined prokaryotes more in terms of what they lack than by any positive attributes, but those differences sufficed. The distinctive property of bacteria and blue-green algae is the procaryotic nature of their cells. It is on this basis that they can be clearly segregated from all other protists (namely, other algae, protozoa, and fungi), which have eucaryotic cells.⁴ Until very recently, few would have questioned the judgment that this basic divergence in cellular structure . . . represents the greatest single evolutionary discontinuity to be found in the present day world.⁵

FIGURE 1.1. Eukaryotes (a) and prokaryotes (b). Schematic sketches of generalized cells; note the disparity in size and architectural complexity.

The division into two kinds of organisms, eukaryotes and prokaryotes, was quickly and enthusiastically accepted and was soon reflected in the large-scale classification of living things. In 1969, when the ecologist Robert Whittaker revised the scheme he had formulated a decade earlier, he divided up the world among five kingdoms—four eukaryotic and one prokaryotic.⁶ Animals, plants, fungi and protists (or protoctists, in Margulis’s terminology) compose eukaryotes. All the bacteria—and only bacteria—were placed in the kingdom Monera. The scheme omitted viruses, which are not made of cells. Five kingdoms were never intended as a statement about who begat whom, but came to be taken as such: the presumption was, and commonly still is, that prokaryotes preceded eukaryotes and were the latter’s evolutionary precursors.

Five kingdoms proved to be a practical system for putting in order the overwhelming diversity of life on earth; writers of textbooks, obliged to survey the landscape and make it comprehensible to students, found it indispensable. But it must be said that as a guide to the evolution of life, the scheme is profoundly misleading. It puts all five kingdoms on an equal footing, implying that the difference between prokaryotes and eukaryotes is of the same kind and magnitude as that between animals and plants. It gives no clue to the gulf of time that separates the familiar multicellular creatures from the microbial world. And there is surely something lacking in a scheme that covers all of life but has no place for viruses. It is true that viruses are not cellular in nature and are obligatory parasites upon other organisms; whether viruses should be considered living depends on your definition of life.⁷ But they are made of the same kinds of molecules as true living things, reproduce with heredity, and evolve all too quickly; they are linked to the great tree of life and must eventually be represented there. Just how drastically our perceptions had to change only became clear with the development of novel, molecular methods to assess relationships among living things and explore the patterns of descent.

But before we go there, let us pause and consider what the concept of the cell means today. A century ago, it meant first and foremost a structural motif: a droplet of cytoplasm, a nucleus, perhaps some organelles, and a plasma membrane to separate inside from outside. The majority of living things is, indeed, constructed upon this plan; but we know so many exceptions and variations that its universality is no longer obvious. The cells of eukaryotes and prokaryotes differ profoundly in size and organization, and each comes in many versions. Discrete nuclei and organelles are common but not indispensable. And many highly successful organisms live as collectives in which numerous nuclei inhabit a common cytoplasm (fungi, oömycetes, many algae, also muscles). A membrane that segregates the cytoplasm from the rest of the world still seems an absolute requirement (to me, at least), but even this has been called into question.⁸

What, then, is the cell that we should praise it as a cornerstone of biological science? Perhaps we should look beyond the architectural commonalities and emphasize that cells are the minimal units capable of underpinning the phenomenon of life. Life, at least the kind we know, is unavoidably complicated. To metabolize, grow, reproduce, and evolve requires a system made up of thousands of collaborating molecules, spatially organized within a sheltering boundary. Discrete units, the gametes, are necessary at least once in a life cycle, to evade the inevitable ravages of time and start afresh with a clean slate. Single cells are the smallest units that meet these requirements, but more elaborate variations are possible. Nature is endlessly flexible and will endorse whatever works in any particular milieu.

Molecular Systems of Daunting Complexity

When examined under the light microscope, most bacterial cells present no more than tiny plain blobs, commonly cylindrical or spheroidal. Modern staining technology, and even more so the electron microscope, reveal structure and order within: flagella and other appendages, a multilayered envelope, various granules, a nucleoid, and, in some instances, internal membranes or a cytoskeleton. When set beside eukaryotic cells with their intricate internal architecture, prokaryotic ones do appear simple; but that illusion quickly vanishes when one turns from the cellular level to the molecular.

Take E. coli, that workhorse of biochemistry and molecular biology, and of all living creatures the one best understood. A single cell takes the form of a short rod, a cylinder some 2 micrometers long and 0.8 wide, with rounded caps. Under optimal conditions, 20 minutes suffice for each cell to elongate, divide, and produce 2 where there had been 1 before. But what a prodigious task this is! In that brief span of time the original cell will have produced some 2 million protein molecules, potentially of 4,000 different kinds; some 22 million lipid molecules, composing 60 varieties; 200,000 molecules of various RNAs; and nearly 1,000 species of small organic substances, some 50 million molecules in all. It will also have duplicated two unique giant molecules. One is the circular, double-stranded DNA helix, consisting of about 4.6 million nucleotide pairs; were it uncoiled, it would stretch for 1,600 micrometers. The other is the peptidoglycan layer of the cell wall, composed of some 2 million repeating units cross-linked into a huge bag-shaped molecule that encases the whole cell. All these are crammed and folded into a volume of about 1 cubic micrometer, a minute capsule filled with a concentrated gel whose properties bear little resemblance to the dilute solutions that laboratory scientists prefer.⁹

Bacterial cells supply instructive, and relatively simple, subjects for reflection on the nature and reach of biological order. The molecules of life compose but a minute sample of all possible carbon-based structures, and those that make up E. coli constitute a subset of that sample. Their structures and abundance are specified, directly or indirectly, by a roster of some 4,200 genes inscribed in the great DNA database; gene expression is regulated in accordance with the needs of the system as a whole, making the composition of the cells a relatively regular and predictable feature. So order is chemical in the first instance, but it is also spatial: many molecules have a habitation and an address in cell space. The cell’s DNA is not a tangle of spaghetti but carefully bundled into a bunch of loops, located at the cell’s center and linked at definite loci to the plasma membrane. Small metabolites and some proteins are free to diffuse within the cytoplasmic gel, but many proteins, lipids and polysaccharides are bound up in one complex or another. Proteins are the operative components of molecular machines that perform physiological tasks on behalf of the collective: ribosomes, replicases, ATP synthases, redox chains, flagella, spliceosomes—not to mention the plasma membrane and cell wall. Much of this machinery occupies more-or-less fixed positions in cell space; even individual proteins often perform functions that depend on their being present at a specific location at a particular time. A cytoskeleton supplies tracks that localize proteins and integrate cell space. And order is also a matter of function, or purpose: the activities of the parts are interconnected by a network of regulatory signals that organizes the cacophony of rambunctious molecules into an orchestra that performs as a unit. Unity is immediately apparent in the cell’s morphology, in the present instance a short cylinder with rounded ends. The more you reflect on cellular order and complexity the more marvelous it appears, and the more it cries out for explanation. Physiologists want to know how cells put in place all those levels of order, from the nanometer scale of molecules to the micrometer or millimeter scale of microbes, and how order is carried from one generation to the next. Evolutionary biologists ask how organized structures changed over time, and how they arose out of the formless world of chemistry and physics; and the latter will be the subject of this book.

Few biologists question the assertion that a cell is a highly organized molecular system of daunting complexity, but they are sure to disagree on just what these terms mean. For the purposes of this book, the common usage will suffice. A system, according to my Collins English Dictionary, is a group or combination of interrelated, interdependent or interacting elements forming a collective entity.¹⁰ Order refers to the regularity and predictability of the parts and their arrangement. Organization designates a special sort of order, one that has purpose. In biology, we prefer to call that function: ribosomes have a function in a larger entity, the orderly orbit of the earth does not. Living creatures of all kinds, prokaryotic as well as eukaryotic and unicellular no less than multicellular, will be informally referred to as organisms. But that word echoes with deeper meaning: for Immanuel Kant, an organism was an entity whose parts work together to produce the organism and all its parts. Unlike machines, which are made, organisms make themselves. The most ambiguous of all these terms is complexity, which commonly means precisely what the user wants it to mean. I shall use it as an indication of the number of parts in a system, the degree of difference among the parts, and the variety of their interactions, in much the same way as do Daniel McShea and Robert Brandon.¹¹ When a system is described as complex, it means that its parts are numerous and diverse, and