MOLECULAR BIOLOGY OF
`THE CELL
`
`Bruce Alberts - Dennis Bray
`Julian Lewis - Martin Raff - Keith Roberts
`
`James D. Watson
`
`
`
`Mylan v. Genentech
`Garland Publishing, Inc.
`R°2016 007 3
`IPR2016-00710
`N
`Y k & L
`d
`fl
`'
`ew or Pagel on on Genentech Exhibit 20 8
`Genentech Exhibit 2018
`Page 1
`
`
`
`

`
`
`
`
`
`“Long ago it became evident that the key to every biological problem must
`finally be sought in the cell, for every living organism is, or at sometime has
`been, a cell.”
`
`
`
`Edmund B. Wilson
`The Cell in Development and Heredity
`3rd edition, 1925, Macmillan, Inc.
`
`
`
`Bruce Alberts received his Ph.D. from Harvard University and is
`currently a Professor in the Department of Biophysics and
`Biochemistry at the University of California Medical School in San
`Francisco. Dennis Bray received his Ph.D. from the Massachusetts
`Institute of Technologz and is currently a Senior Scientist in the
`Medical Research Council Cell Biophysics Unit at King’s College
`London. Julian Lewis received his D.Phil. from Oxford University and
`is currently a Lecturer in the Anatomy Department at King's College
`London. Martin Rafi” received his M.D. degree from McGill University
`and is currently a Professor in the Zoology Department at University
`College London. Keith Roberts received his Ph.D. from Cambridge
`University and is currently Head of the Department of Cell Biology at
`the John Innes Institute, Norwich. James D. Watson received his
`Ph.D. from the University of Indiana and is currently Director of the
`Cold Spring Harbor Laboratory. He is the author of Molecular Biology
`of the Gene and, with Francis Crick and Maurice Wilkins, won the
`Nobel Prize in Medicine and Physiology in 1962.
`
`Cover photograph kindly provided by Michael Verderame and Robert
`Pollack of Columbia University. The fluorescein-phalloidin used to
`stain the actin cables was the generous gift of Drs. Theodor
`Wieland and A. Deboben of the Max Planck Institute, West Germany.
`The photograph is of a mouse fibroblast that had been transformed
`to anchorage-independent growth by the virus Simian Virus 40 (SV40)
`and subsequently selected for anchorage-dependent growth. This
`particular cell was stained for SV40 large T antigen (red) and
`fluorescein-phalloidin (green), which specifically stains F actin.
`
`
`
`© 1983 by Bruce Alberts, Dennis Bray, Julian Lewis, Martinlfiaff,
`Keith Roberts, and James D. Watson.
`
`All rights reserved. No part of this book covered by the copyright
`hereon may be reproduced or used in any form or by any means——
`graphic, electronic, or mechanical, including photocopying,
`recording, taping, or information storage and retrieval systems—
`without permission of the publisher.
`
`Library of Congress Cataloging in Publication Data
`Main entry under title:
`
`Molecular biology of the cell.
`Includes bibliographies and index.
`1. Cytology. 2. Molecular biology. I. Alberts,
`Bruce, 1938-
`[DNLM: 1. Cells. 2. Molecular
`biology. QH 581.2 M718]
`QH581.2.M64 1983
`ISBN 0-8240-7282-0
`
`82-15692
`
`574.87
`
`Published by Garland Publishing, Inc.
`136 Madison Avenue, New York, NY 10016
`
`Printed in the United States of America
`
`15141312111098765432
`
`
`
`Page 2
`Page 2
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`

`
`
`
` The Evolution
`
`
` e Cell as
`
`
`
`All living creatures are made of cells-—small membrane—bounded compart-
`ments filled with a concentrated aqueous solution of chemicals. The simplest
`forms of life are solitary cells that propagate by dividing in two. Higher orga-
`nisms, such as ourselves, are like cellular cities in which groups of cells per-
`form specialized functions and are linked by intricate systems of communi-
`cation. In a sense, cells are halfway between molecules and man. We study"
`them to learn, on the one hand, how they are made from molecules and, on
`the other, how they cooperate to make an organism as complex as a human
`being.
`All organisms, and all of the cells that constitute them, are believed to
`have descended from a common ancestor cell by evolution. Evolution involves
`two essential processes: (1) the occurrence of random variation in the genetic
`information passed from an individual to its descendants and (2) the selection
`of genetic information that helps its possessors to survive and propagate’.
`Evolution is the central principle of biology, helping us to make sense of the
`bewildering variety in the living world.
`This chapter, like the book as a whole, is concerned with the progression
`from molecules to multicellular organisms. It discusses the evolution of the
`cell, first as a living unit constructed from smaller parts, and then as a building
`block for larger structures. Through evolution, we introduce the cell compo-
`nents and activities that are to be treated in detail, in broadly similar sequence,
`in the chapters that follow. Beginning with the origins of the first cell on earth,
`we consider how the properties of certain types of large molecules allow
`hereditary information to be transmitted and expressed, and permit evolution
`to occur. Enclosed in a membrane, these molecules provide the essentials of
`a self-replicating cell. Following this, we describe the major transition that
`Occurred in the course of evolution, from small bacteriumlike cells to much
`larger and more complex cells such as are found in present—day plants and
`animals. Lastly, we suggest ways in which single free—llving cells might have
`given rise to large multicellular organisms, becoming specialized and coop-
`erating in the formation of such intricate organs as the brain.
`
`
`
`

`
`
`
`6)
`
`electric
`discharge
`
`4 The Evolution of the Cell
`
`Clearly, there are dangers in an evolutionary approach: the large gaps in
`our knowledge can be filled only by speculations that are likely to be wrong
`in many details. But there is enough evidence from fossils and from compar-
`ative studies of present-day organisms and molecules to allow us to make
`intelligent guesses about the major stages in the evolution of life.
`
`From Molecules to the First Cell‘
`
`Simple Biological Molecules Can Form
`Under Prebiotic Conditions
`
`The conditions that existed on the earth in its first billion years are still a
`matter of dispute. Was the surface initially molten? Did the atmosphere con-
`tain ammonia, or methane? Everyone seems to agree, however, that the earth
`was a violent place with volcanic eruptions, lightning, and torrential rains.
`There was little if any free oxygen and no layer of ozone to absorb the harsh
`ultraviolet radiation from the sun.
`Simple organic molecules (that is, molecules containing carbon) are likely
`to have been produced under such conditions. The best evidence for this
`comes from laboratory experiments. If mixtures of gases such as CO2, CH4,
`NH3, and H2 are heated with water and energized by electrical discharge or
`by ultraviolet radiation, they react to form small organic molecules——usually
`a rather small selection, each made in large amounts (Figure 1-1). Among
`these products are a number of compounds, such as hydrogen cyanide
`H\
`/C=O , that readily undergo further reac-
`H
`
`lH~CEN) and formaldehyde
`
`tions in aqueous solution (Figure 1-2). Most important, the four major classes
`of small organic molecules found in cells——-amino acids, nucleotides, sugars,
`and fatty acids~——are generated.
`While such experiments cannot reproduce the early conditions on the
`earth exactly, they make it plain that the formation of organic molecules is
`surprisingly easy. And the developing earth had immense advantages over any
`human experimenter; it was verylarge and could produce a wide spectrum
`of conditions. But above all, it had much more time——hundreds of millions of
`years. In such circumstances it seems very likely that, at some time and place,
`many of the simple organic molecules found in present-day cells accumulated
`in high concentrations.
`
`Polynucleotides Are Capable of Directing
`Their Own Synthesis
`
`Simple organic molecules such as amino acids and nucleotides can associate
`to form large polymers. One amino acid can join with another by forming a
`peptide bond, while two nucleotides can join together by a phosphodiester
`bond. The repetition of these reactions leads to linear polymers known as
`polypeptides and polynucleofides, respectively. In present-day living orga-
`nisms, polypeptides——~knoWn as proteins——and polynucleotides-——in the form
`of both ribonucleic acids (RNA) and deoxyribonucleic acids (DNA)——are com-
`monly viewed as the most important constituents. A restricted set of 20 amino
`acids constitute the universal building blocks of the proteins, while RNA and
`DNA molecules are constructed from four types of nucleotides each. One can
`only speculate as to why these particular sets of monomers should have been
`selected for biosynthesis in preference to others that are chemically similar.
`
`9
`
`Figure 1——1 A typical experiment
`simulating conditions on the
`primitive earth. Water is heated in a
`closed apparatus containing CH4,
`NH3, and H2, and an electric
`discharge is passed through the
`vaporized mixture. Organic
`compounds accumulate in the U-tube
`trap .
`
`ecno
`
`CH3COOH
`
`NH2CH2COOH
`
`HCOOH
`
`cH3cH2cooH
`OH
`
`NH2cH2cooH
`CH3
`
`l\‘lH- CH2COOH
`CH3
`
`NH2cH2cooH
`9'2COOH
`
`formaldehyde
`
`acetic acid
`
`glycine
`
`formic acid
`
`lactic acid
`
`alanine
`
`sarcosine
`
`hydrogen cyanide
`
`urea
`
`aspartic acid
`
`Figure 1-4:. A few of the compounds
`that might be formed in the
`experiment described in Figure 1-1.)
`Compounds shown in color are
`important components of present-day
`living cells.
`
`
`
`
`
`

`
`
`
`From Molecules to the First Cell
`
`5
`
`The earliest polymers may have formed in several way‘s-for example,
`by the heating of dry organic compounds or by the catalytic activity of high
`concentrations of inorganic polyphosphates. The products of similar reactions
`in the test tube are polymers ofvariable length and random sequence in which
`the amino acid or nucleotide added at any point depends mainly on chance
`(Figure 1-3). However, once a polymer has formed, it is able to influence the
`formation of other polymers. Polynucleotides, in particular, have the ability to
`specify the sequence of nucleotides in new polynucleotides by acting as tem-
`[ates for the polymerization reactions. For example, a polymer composed of
`
`one nucleotide (polyuridylic acid, or poly U) can serve as a template for the
`synthesis of a second polymer composed of another type of nucleotide (poly-
`adenylic acid, or poly A). Such templating depends on the fact that one poly-
`mer preferentially binds the other. By lining up the subunits required to make
`poly A along its surface, poly U promotes the formation of poly A (Figure 1—4).
`Specific pairing between complementary nucleotides probably played a
`crucial part in the origin of life. Consider, for example, a polynucleotide such
`as RNA, made of a string of four nucleotides, containing the bases uracil (U),
`adenine (A), cytosine (C), and guanine (G). Because of complementary pairing
`between the bases A and U and between the bases G and C, when RNA is
`added to a mixture of activated nucleotides under conditions that favor po~
`lymerization, new RNA molecules are produced in which nucleotides are joined
`in a sequence that is complementary to the first. That is, the new molecules
`are rather like a mold of the original, with each A in the original corresponding
`to a U in the copy, and so on. The sequence of nucleotides in the original
`RNA strand contains information that is, in essence, preserved in the newly
`formed complementary strands. A second round of copying, with the com-
`plementary strand as a template, restores the original sequence (Figure 1-5).
`Such complementary templating mechanisms are elegantly simple, and
`they lie at the heart of information—transfer processes in biological systems’.
`Genetic information contained in every cell is encoded in the sequences of
`nucleotides in its polynucleotide molecules, and this information is passed
`on (inherited) from generation to generation by means of complementary base-
`pairing interactions.
`Rapid formation of polynucleotides in a test tube requires the presence
`of specific protein catalysts, or enzymes, which would not have been present
`in the “prebiotic soup.” However, less efficient catalysts in the form of minerals
`or metal ions would have been present; and, in any case, catalysts only speed
`up reactions that would occur anyway given sufficient time. Since both time
`and a supply of chemically reactive nucleotide precursors were available in
`abundance, it is likely that slowly replicating systems of polynucleotides be-
`came established in the prebiotic conditions on earth.
`
`
`
`H20
`
`
`
`H20
`
`c4c—A
`
`uqe—cHA—q
`
`A—A
`
`G-G-)0-(U*U(-U-(A—C)
`
`Figure M3 Nucleotides of four
`kinds (here represented by the single
`letters A, U, G, and C) can undergo
`spontaneous polymerization with the
`loss of water. The product is a
`mixture of polynucleotides that are
`random in length and sequence.
`
`C(W)!!!>
`
`Figure 1-4 Preferential binding
`occurs between pairs of nucleotides
`(C with G and A with U) by relatively
`weak chemical bonds (above). This
`
`pairing enables one polynucleotide to
`act as a template for the synthesis of
`another (left).
`
`

`
`Figure 1—-5 Replication of a
`polynucleotide sequence (here an
`RNA molecule). In step 1, the original
`RNA molecule acts as a template to
`form an RNA molecule of
`
`complementary sequence. In step 2,
`this complementary RNA molecule
`itself acts as a template, forming RNA
`molecules of the original sequence.
`Since each templating molecule can
`produce many copies of the
`complementary strand, these
`reactions can result in the
`
`“multiplication" of the original
`sequence.
`
`6
`
`The Evolution of the Cell
`
`step 1
`
`[u—c—(c—{A}—c—c—u(
`ORIGINAL SEQUENCE
`COMPLEMENTARY
`SEQUENCE FORMS
`F0};
`8
`COMJLEMENTARY
`ORlGl'\lAL SEQUENCE
`SEQUENCE
`
`
`
`Self—replicating Molecules Undergo Natural Selection
`
`Under favorable conditions, a polynucleotide molecule in a rich soup of nu-
`cleotides is able to multiply, with each copy of the original serving as the
`parentrfor new copies. However, many errors will inevitably occur in the copy-
`ing process, especially under primordial conditions. New and imperfect copies
`of the original will be propagated. In time, therefore, the sequence of nucleo-
`tides in the original polynucleotide molecule will change until the information
`it once represented is entirely lost (Figure 1~6).
`But polynucleotides are not just strings of symbols that carry information
`in an abstract way. They have chemical personalities that affect their behavior.
`The specific sequence of nucleotides governs the properties of the whole
`molecule, especially how it folds up in solution. Just as the nucleotides in a
`polynucleotide can pair with free complementary nucleotides in their envi-
`ronment to form a new polymer, so they can pair with complementary nu-
`cleotide residues within the polymer itself. A sequence GGGG in one part of
`a polynucleotide chain can form a relatively strong association with a CCCC
`sequence in another region of the molecule. Such associations produce var-
`ious three—dimensional folds, and the molecule as a whole takes on a unique V
`shape that depends entirely on the sequence of its nucleotides (Figure 1-7).
`The three-dimensional folded structure of a polynucleotide affects both
`its stability and its ability to replicate, so that not all polynucleotide shapes
`will be equally successful in a replicating mixture. Some will be too long or
`too tightly folded to act as efficient templates. Others might be unstable under
`the prevailing conditions. In fact, it has beendemonstrated in laboratory stud-
`ies that replicating systems of RNA molecules undergo a form of natural se-
`lection and that different favorable sequences will eventually predominate,
`depending on the exact conditions.
`A polynucleotide such as an RNA molecule therefore has two important
`characteristics: it carries information encoded in its nucleotide sequence that
`it passes on by the process of replication, and it has a unique folded structure
`that determines how it will function and respond to external conditions. These
`two features——one informational, the other functional—are the two essential
`
`’
`
`ingredients required for evolution to occur. The nucleotide sequence of an
`RNA molecule is analogous to the hereditary information, or genotype, of an
`organism. The folded three—dimensional structure is analogous to the phen-
`otype———the expression of the hereditary information upon which natural se-
`lection operates.
`
`Figure :t——6 Changes in the sequence of an RNA molecule
`can Occur through errors in replication. Here a particular
`“lineage" is traced in color showing how the RNA sequence
`AACCGU changes progressively to UGUAAC through a series
`of copying errors. Many other sequences will be generated at
`the same time, as indicated by the multiple arrows.
`
`
`
`

`
`
`
`
`
`From Molecules to the First Cell 7
`
`Figure '1-7 Nucleotide pairing
`between different regions of the same
`polynucleotide (RNA) chain causes
`the molecule to adopt a distinctive
`shape.
`
`c
`
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`
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`C
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`
`G G G A
`
`
`
`Information Flows from Polynucleotides to Polypeptides
`
`The suggestion, therefore, is that between 3.5 and 4 billion years ago, some-
`where on earth, self—replicating systems of polynucleotides began the process
`of evolution. Polymers with different nucleotide sequences competed for the
`available precursor materials to construct copies of themselves, just as orga-
`nisms now compete; success depended on the accuracy and the speed with
`which the copies were made and on the stability of those copies.
`.
`However, while the structure of polynucleotides is well suited for infor-
`mation storage and replication, these molecules are not sufficiently versatile
`to provide all the structural and functional building blocks of a living cell.
`Polypeptides, on the other hand, are composed of many different amino acids,
`and, as will be discussed in Chapter 3, their diverse three-dimensional forms,
`which often bristle with reactive sites, make them ideally suited to a wide
`range of structural and chemical tasks. Even random polymers of amino acids
`produced by prebiotic synthetic mechanisms are likely to have had catalytic
`properties, some of which could have enhanced the replication of RNA mol-
`ecules. Some classes of polypeptides would therefore have been extremely
`useful to a replicating system, especially if they could be tailor~made. Polynu-
`cleotides that helped guide the synthesis of specific polypeptides in their
`environment would have had a great advantage in the evolutionary struggle
`for survival (Figure 1—8)
`Yet how could polynucleotides exert such control? How could the in- A
`formation encoded in their sequence specify the sequences of polymers of a
`different type? In present-day organisms, RNA directs the synthesis of poly-
`PBptides———that is, protein synthesis-—-but it is a process that requires re-
`markably elaborate biochemical machinery. One RNA molecule carries the
`
`

`
`
`
`8
`
`The Evolution of the Cell
`
` replication cycle of RNA
`
`Figure 1-8 Proteins can act as
`efficient catalysts of chemical
`reactions such as the formation of
`
`nucleotides or their polymerization
`into RNA. Therefore, an RNA molecule
`that can direct the synthesis of an
`appropriate protein is able to
`accelerate its own replication, as
`illustrated schematically here.
`
`%AFA4cHcHuHA%c—u primitive
`
`"‘ *
`//l\\
`1
`\\\
`
`\\
`
`protein with
`enzymatic
`activity
`
`/
`
`//
`
`
`
`genetic information for a particular polypeptide, while a set of other RNA
`molecules bind amino acids; the two types of RNA molecules form comple-
`mentaty base pairs with one another to enable sequences of nucleotides in
`the informational RNA molecule to direct the incorporation of specific amino
`acids into a growing polypeptide chain. Assembly of new proteins takes place
`on the surface of rz'b0somes—complex particles composed of several large
`RNA molecules and more than 50 different types of protein. How such a
`complex mechanism arose in evolution is still a mystery, although pieces of
`the puzzle are falling into place. One of the most fascinating sources of evi-
`dence is the genetic “dictionary,” or genetic code, by which nucleotide triplets
`are translated into amino acids. Since the code is essentially the same in all
`living organisms, it must have become fixed at a very early stage in evolution,
`and it is likely to contain traces of the way that primordial translation was
`achieved.
`
`Whatever the preliminary steps of evolution may have been, once RNA
`molecules were able to direct the synthesis of proteins, they had potentially
`at their disposal an enormous workshop of chemical tools. It was now possible
`in principle to synthesize enzymes that could catalyze a large range of chem-
`ical reactions, including the synthesis of more proteins and RNA molecules.
`Once the evolution of nucleic acids had thus advanced to the point of speci-
`fying enzymes to aid in their own manufacture, the proliferation of the rep-
`licating system would have been immensely speeded up. The potentially ex-
`plosive nature of such an autocatalytic process can be seen today in the life
`cycle of some bacterial viruses: after they have entered a bacterium, such
`viruses direct the synthesis of proteins that catalyze selectively their own
`replication, so that within a short time they take over the entire cell (Figures
`1~—9 and 1-10).
`
`Membranes Defined the First Cell
`
`The appearance of protein synthesis controlled by nucleic acids was no doubt
`one of the crucial events leading to the formation of the first cell. Another
`must have been the development of an outer membrane. The proteins syn-
`thesized under the control of a certain species of RNA would not facilitate
`reproduction of that species of RNA unless they were retained in the neigh—
`borhood of the RNA; moreover, as long as these proteins were free to diffuse
`among the population of replicating RNA molecules, they could benefit equally
`any competing species of RNA that might be present. If a variant RNA arose
`that made a superior type of enzyme, the new enzyme could not contribute
`selectively to the survival of the variant RNA in its competition with its fellows.
`Selection of RNA molecules according to the quality of the proteins that they
`
`

`
`
`
`Figure 1-10) and injects its DNA into
`the bacterial cell. Within 5 minutes,
`this DNA has directed the synthesis
`of a set of specific proteins, some of
`which degrade the DNA of the host
`bacterium, while others catalyze the
`replication of the viral DNA. The
`dense particles seen in the cell 15
`» minutes after infection are immature
`
`Figure 1-10 A higher magnification
`micrograph of a bacterial cell that has
`been infected with virus particles for
`more than an hour. The infectious
`
`cycle is almost complete, and the
`bacterial cell is about to burst open,
`releasing several hundred new
`infective virus particles to the
`surroundings. The virus shown in
`this micrograph and in the
`micrographs of Figure 1-9 is
`bacteriophage T4. (Courtesy of E.
`Kellenberger.)
`
`Figure 1--9 Sequence of electron
`micrographs showing the growth of a
`virus inside a bactelial cell. Infection
`
`begins when the virus attaches to the
`outside of the bacterium (see also
`
`virus particles consisting of viral DNA
`packed into spherical shells of
`protein (the shells are first made
`separately, as shown in the inset).
`Virus particles continue to mature
`and accumulate in the cell, as seen in
`
`the 30-minute specimen. (Courtesy of
`E. Kellenberger.)
`
`

`
`
`
`10
`
`The Evolution of the Cell
`
`Ow’
`’/:5
`S’”"
`
`
`
`
`primarily available for its own use (Figure 1-11).
`replication cycle
`All present—day cells are surrounded by a plasma membrane, com—
`/
`posed of phospholipids and proteins. In the electron microscope such mem-
`Ga---RNA
`branes appear as sheets about 7 nm thick, with a distinctive three-layered
`fig:
`appearance due to the tail—to—tail packing ofthe phospholipid molecules. Ar—
`\
`:
`tificial membranes with a very similar appearance can be made in the test C \\
`//7”‘
`/’
`tube simply by mixing phospholipids and water together. Under suitable con-
`,:‘)\g.______ ‘
`.
`_
`_
`ditions such artificial membranes round up into closed vesicles with diame—
`/ ‘\
`:,:'Z':,l::,2/9
`ters between 1 and 10 um. Although these vesicles are inert, like soap bubbles,
`/
`\\
`it is easy to imagine that by enclosing a distinct population of molecules they
`‘;\‘,’f:
`could form a spatially isolated functional unit.
`It has been postulated that the first cell was formed when phospholipid
`molecules in the prebiotic soup spontaneously assembled into such mem-
`branous structures, enclosing a self—replicating mixture of RNA and protein
`molecules. Once sealed within a closed membrane, RNA molecules could
`begin to evolve, not merely on the basis of their own structure, but also ac-
`cording to the proteins they could make: the nucleotide sequences of the RNA
`molecules could now become expressed in the character of the cell as a whole.
`
`primitive
`enzyme
`
`
`Mycoplasmas Are the Simplest Living Cells
`The picture we have presented is, of course, speculative: there are no fossil 61”‘
`records that trace the origins of the first cell. Nevertheless, there is persuasive
`evidence from present—day organisms, and from experiments, that the broad
`8,...
`features ofthis evolutionary story are correct. The prebiotic synthesis ofsmall
`molecules, the self-replication of RNA molecules, the translation of RNA se-
`Figure 1-11 Schematic drawing
`quences into amino acid sequences, and the assembly of lipid molecules to
`showing the evolutionary advantage
`form membrane-bounded compartments——all presumably occurred to gen-
`of Cell-like Compartments. In a mixed
`erate the first cell 3.5 or 4 billion years ago.
`POPUIWOD Of Se1f‘1"9P1iC<"1fin8 RNA
`It is useful to compare this putative first cell with the simplest present-
`day cells,
`the mycoplasmas. Mycoplasmas are small bacteriumlike orga— molecules Capable Of Protein
`nisms that normally lead a parasitic existence in close association with animal
`Synthesis (as illustrated in Fig”? P8)’
`and plant cells (Figure 1-12). Some have a diameter of about 0.3 pm and con-
`any Improved fan“ of RNA that Is
`,
`tain enough nucleic acid to direct the synthesis of about 750 different pro— able to produce a more useful pmtem
`,
`,
`_
`_
`,
`must share this protein with all of its
`teins, which may be the minimum number of proteins that a cell needs to
`Competitors. However’ if the RNA is
`survive.
`_
`~
`_
`enclosed within a compartment, such
`One important difference between the first cell as we have described it
`as a lipid membrane, then any
`and a mycoplasma (or indeed any other present—day cell) is that the hereditary
`protein it makes is confined for its
`information in the latter is stored in DNA rather than RNA. Both types of
`own use; the RNA can therefore be
`selected on the basis of its making a
`better protein.
`
`\
`
`compartment
`
`(Courtesy of J. Burgess.)
`
`Figure 1-12 Spiroplasma citrii, a
`mycoplasma that grows in plant cells.
`
`

`
`From Procatyotes to Eucaryotes
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`11
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`polynucleotides are found in present-day cells, but they function in a collab-
`orative manner, each having evolved to perform specialized tasks. Small chem-
`ical differences fit the two kinds of molecules for distinct functions. DNA serves
`as the permanent repositoty of genetic information. Unlike RNA, it exists prin-
`cipally in a double-stranded form composed of a pair of complementary poly-
`nucleotide molecules. Not only is genetic information that is stored in this
`Way made more stable, but the double-stranded arrangement permits the
`operation of a repair mechanism: an intact strand serves as the template for
`the correction or repair of an associated damaged strand. DNA guides the
`synthesis of specific RNA molecules, again by the principle of complementary
`base-pairing,‘ though now this pairing is between slightly different types of
`nucleotides. The resulting single-stranded RNA molecules then perform the
`two other primeval functions: they direct protein synthesis and in some sit-
`uations they have a structural role not unlike that of proteins.
`In addition to its various classes of polynucleotides, the mycoplasma cell
`contains many enzymes and structural proteins, some in its interior and some
`embedded in its membrane; these together synthesize essential small mole-
`cules that are not provided in the environment, redistribute the energy needed
`to drive biosynthetic reactions, and maintain appropriate chemical conditions
`inside the cell. The evolution of these latter metabolic functions will be dis-
`cussed in the following section.
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`Summary
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`Living cells probably arose on earth by the spontaneous aggregation of mole-
`cules about 3.5 billion years ago. From our knowledge ofpresent-day organisms
`and the molecules they contain, it seems that at least three steps must have
`occurred before the first cell emerged: (1) polymers ofRNA capable of directing
`their own replication through complementary base—pairing interactions had to
`be formed; (2) mechanisms by which an RNA molecule could direct the syn-
`thesis of a protein had to be developed; and (3) a lipid membrane had to as-
`semble to enclose the self—replicating mixture of RNA and protein molecules.
`At some later stage in the evolutionary process, DNA took the place of RNA as
`the hereditary material.
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`From Procaryotes to Eucaryotes”
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`It is thought that all organisms living now on earth derive from one single
`primordial cell born several billion years ago. This cell, outreproducing its
`Competitors, took the lead in the process of cell division and evolution that
`would eventually cover the earth in green, change the composition of its
`atmosphere, and make it the home of intelligent life. The family resemblances
`between all organisms seem too strong to be explained in any other way. One
`important landmark along this evolutionary road occurred about 1.5 billion
`years ago, when there wasa transition from small cells with a relatively simple
`Internal structure-——the so-called procaryotes, which include the various types
`Of bacteria——to the larger and radically more complex eucaryotic cells such
`as are found in higher animals and plants.
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`Procaryotic Cells Are Structurally Simple
`But Biochemically Diverse
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`Bacteria are the simplest organisms found in most natural environments.
`They ‘3l‘e Spherical or rod-shaped cells, commonly several turn in linear di-
`menSl0I1 (Figure 1—13). They often possess a tough protective coat, called a
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`Spiri//um
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`a spirochete
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`its
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`Anabaena (a cyanobacterium)
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`large Bacillus
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`Escherichia coli
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`Staphylococcus
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`R/cketts/a
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`W 3species0i‘
`Mycop/“ma
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`>(
`10m
`(<
`Figure 1-13 Some procaryotic cells
`drawn to scale.
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`12;
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`The Evolution of the Cell
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`cell wall, beneath which a plasma membrane encloses a single cytoplasmic
`compartment containing DNA, RNA, proteins, and small molecules. In the
`electron microscope this cell interior appears as a more or less uniform matrix
`(see top panel of Figure 1~9l.
`Bacteria are small and can replicate quickly by simply dividing in two
`by binary fission. When food is plentiful, “survival of the fittest” generally
`means survival of those that can divide the fastest. Under optimal conditions,
`a single procaryotic cell can divide every 20 minutes and thereby give rise to
`4 billion cells (approximately equal to the present human population on earth)
`in less than 11 hours. The ability to divide quickly enables populations of
`bacteria to adapt rapidly to changes in their environment. Under laboratory
`conditions, for example, a population of bacteria maintained in a large vat will
`evolve within a few weeks by spontaneous mutation and natural selection to
`utilize new types of sugar molecules as a carbon source.
`In nature, bacteria live in an enormous variety of ecological niches, and
`they show a corresponding richness in their underlying biochemical com-
`position. Two distantly related groups can be recognized: the eubacteria, which
`are the commonly encountered forms that inhabit soil, water, and living
`organisms; and the archaebacteria, which are found in such incomme-
`dious environments as bogs, ocean depths, salt brines, and hot acid springs
`(Figure 1—~14).
`There exist species of bacteria that can utilize virtually any type of or—
`ganic molecule as food, including sugars, amino acids, fats, hydrocarbons,
`polypeptides, and polysaccharides. Some are even able to obtain their carbon
`atoms from CO2 and their nitrogen atoms from N2. Despite their relative sim—
`plicity, bacteria have survived for longer than any other organisms and still
`constitute the most abundant type of cell on earth.
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`Metabolic Reactions Evolve
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`A bacterium growing in a salt solution cont