secondly, salts, - pnas · i.e., hc1, hbr,hf,etc., are gaseous, in terrestrial surroundings they...

VOL. 53, 1965 N. A. S. SYMPOSIUM: B. COMMONER 1183

Siever, R., K. C. Beck, and R. A. Berner, "Composition of interstitial waters of modern sedi-ments," J. Geol., 73, 39-73 (1965).

Sill6n, L. G., "The physical chemistry of sea water," in Oceanography, ed. Mary Sears (Wash-ington, D.C.: A.A.A.S., 1961), pp. 549-581.

Turekian, K. K., "The geochemistry of the Atlantic Ocean Basin," Trans. N.Y. Acad. Sci., 26,312-330 (1964).

Wasserburg, G. J., "Comments on the outgassing of the earth," in The Origin and Evolutionof the Atmospheres and Oceans, ed. P. J. Brancazio and A. G. W. Cameron (New York: JohnWiley, 1964), chap. 4.Whitehouse, U. G., and R. S. McCarter, "Diagenetic modification of clay mineral types in arti-

ficial sea water," in Clays and Clay Minerals, Proceedings of the 5th National Conference, NAS-NRC Publication 566 (Washington, D.C.: NAS-NRC, 1958), pp. 81-119.

(Discussion of Dr. Holland's paper)

DR. UREY: Chloride is not a volatile but a soluble ... [inaudible ] ...........FROM THE FLOOR: Would you repeat the comment?DR. HOLLAND: First, Dr. Urey objects to the use of the term volatile for

chloride. Secondly, he feels the major part of the chloride comes from the interiortogether with sodium.On the first point, I think it is really a matter of semantics. Rubey classed chlo-

ride together with the excess volatiles as one of those things that is present on thesurface of the earth in quantities very much larger than can be expected from theweathering of rock.The second question is very difficult to answer right now. I have racked my

brain trying to think of some way to differentiate between chloride that has comeout of volcanoes versus what has come out of hydrothermal solutions. I don'tknow that the distinction is particularly important in terms of the problem at hand,but it would be very nice to know. If you know some way to distinguish the two,I would like to know.DR. UREY: 1\Iy only argument was that while the hydrides of the halogens,

i.e., HC1, HBr, HF, etc., are gaseous, in terrestrial surroundings they form salts,i.e., CaCl2, NaBr, MgF2, etc. It is interesting that the soluble ones are concen-trated at the surface of the earth, whereas the insoluble fluorides are not.

I don't think this is a matter of semantics. I think it is a matter of purely chem-ical characteristics.

BIOCHEMICAL, BIOLOGICAL, AND ATMOSPHERIC EVOLUTION

BY BARRY COMMONER

WASHINGTON UNIVERSITY, ST. LOUIS, MISSOURI

The Problem. -There is a close mutual interaction between the evolution of theatmosphere and the early evolution of life. This paper is intended to analyze thisinteraction relative to its least understood sector: the emergence of the first livingsystems from the primitive environment.

1184 EVOLUTION OF THE EARTH'S ATMOSPHERE PROC. N. A. S.

These considerations suggest that the most distinctive property of the modernliving organism-self-duplication-is not the origin, but rather the culmination,of the primordial events which produced the first living things. They suggest, aswell, that the most primitive role of the nucleic acids relates to their interactionwith exergonic metabolism, the latter being the attribute of modern living systemsto appear earliest in the origin of life. From this beginning, a plausible schemecan be developed to account for the emergence of living organisms from the pre-biotic environment through a gradual transformation of the chemistry of theaqueous organic system on the early earth's surface.

The Limiting Conditions.-It now seems highly probable that the earth's originalatmospheric constituents have largely escaped the planet's gravitational field andthat the modern atmosphere has evolved from material originating in the earth'sinterior (Rubey,l Holland2). The atmosphere derived from degassing of theearth's interior probably consisted chiefly of H20, NH3, N2, CH4, and H2S; oxygenbegan to appear only about 2 billion years ago as a result of newly emerged photo-synthetic systems. The resultant accumulation of ozone accounts for the relativefreedom of the modern earth's surface from lethal ultraviolet radiation.

If the atmospheric oxygen is itself a result of a highly developed biologicalprocess, then the first living things were anaerobes. If the early forms of life wereto be protected from the intense ultraviolet radiation which penetrated the ozone-free atmosphere, then their habitat must have been shielded. However, since anevolutionary change within these primitive organisms gave rise to photosynthesis,their habitat needed to be accessible to visible light. These requirements restrictthe habitat of the primitive anaerobes to a location lying below a layer of waterat least 10 meters thick, but not thick enough to attenuate appreciably the pene-tration of visible light.3These predictions are strikingly confirmed by the growing evidence that the

earliest living things that have left a fossil record may well have been anaerobes,some of which may also have been capable of photosynthesis. These organismsappeared early enough-about 2 billion years ago-to serve as the progenitors ofthe organisms responsible for the later accumulation of oxygen in the atmosphere.4 5Cloud5 has suggested that, in the presence of ferrous iron, oxygen initially pro-duced by primitive photosynthesis would be taken up by the formation of ferricfrom ferrous iron; this could have provided time for the development of new formsthat tolerated, and eventually used, oxygen.

Biological evolution suggests that features that are both ubiquitous and basicare probably primitive. Accordingly, the relative times of origin of variousmetabolic systems are suggested by a comparison of the range of organisms inwhich they now occur. By this test anaerobic metabolism is of earliest origin;every known living organism is capable of some sort of anaerobic metabolism, butonly a smaller number of organisms are capable of either aerobic metabolism orof photosynthesis. Other such considerations suggest the following generaliza-tions regarding the course of metabolic evolution following the original appearanceof living organisms.6 The first true organisms were probably anaerobic hetero-trophs deriving energy from the partial oxidation of the abundant store of geo-chemically produced organic substrates. These forms gave rise to organisms inwhich light-absorption served to enhance anaerobic exergonic metabolism, and


which later evolved photosynthetic systems capable of carbon assimilation. Theprimitive, anaerobic, photosynthetic forms are believed to have given rise toorganisms capable of photolysis of water and the release of molecular oxygen.Aerobes which then evolved established the metabolic foundation of the terrestrialand aquatic organisms which dominate the modern biosphere.That organic substances might have been formed by chemical conversion of

simple constituents of the earth's early atmosphere was first surggested byOparin6 and Haldane.7 This idea has since been elaborated by Wald8 and Blum9and supported by the experiments of Miller and Urey,'0 Calvin,"1 and others.Simple mixtures of substances such as methane, ammonia, and water, when exposedto various forms of incident energy, such as UV radiation, give rise to numerousorganic compounds of the types found in modern living things.

It should be noted that the environment out of which the first forms of lifeemerged must have been replete with liquid water. The evidence for this con-clusion is derived from both geochemical considerations and from the ubiquityand functional importance of water in modern living systems. Indeed, the remark-able fitness of water to support life'2 is now seen as the inevitable consequence ofthe historical fact that life is a system derived from an aqueous environment.An Analysis of the Problem.-We now confront the problem of interest. What

course of evolutionary changes on the prebiotic earth created living organismsalready possessing the basic attributes of the modern living cell: a highly orderedstructure, exergonic metabolism, growth, and self-duplication? In what orderdid these basic features appear as the first living systems emerged from the pre-biotic solution?The foregoing considerations suggest several guiding principles: (i) Evolutionary

events reflect a close interaction between the properties of the living system andthose of the environment. (ii) The principle of biological evolution that relatesubiquity to primitiveness applies as well to the evolution of biochemical systems.(iii) The functional biochemical relationships now observed among the basic at-tributes of living organisms also governed their primary origins.

Figure 1 summarizes diagrammatically the functional relations that connectexergonic metabolism, growth, and replication in modern organisms. Growthinvolves a basic generic process: the synthesis of polymers, such as polysaccharides,lipids, proteins, and nucleic acids from the relevant monomeric residues. Each ofthese polymerizations is an endergonic process, in which the free energy requiredfor polymerization is achieved at the expense of a triphosphonucleotide (oftenATP), that is itself generated in the course of exergonic metabolism. Hence,polymer synthesis and growth cannot proceed in the absence of exergonic metab-olism.A similar relationship couples growth and self-duplication. Self-duplication

involves, on the molecular level, replication of the biochemical specificity of thepolymers (e.g., protein amino acid sequence and nucleic acid nucleotide sequence'3)which occur in living cells. This specificity is achieved as a result of regulatoryprocesses that- determine which of the alternative possible monomer residues islaid down in a particular position during polymer synthesis. Hence, replication isimpossible without polymer synthesis.

Finally, in the modern cell exergonic metabolism is itself dependent on replica-


SPECIFIC AMINO ACID SEQUENCE

arg-leu-prooala...

PEPTIDE-BONDSYNTHESIS

Enzyme ala-tRNASpecificity AMP arg-tRNA \ leu-pro-ala...

(ADP) asp-tRNA m

selection

H-donor H-acceptor mechanism

amino-acyl-AMP (e.g. mRNA)

derivatives

OX. red.Il-donor H-acceptor

freeamino acids

ATP ala

EXERGONIC METABOLISM argasp

FiG. L.-Schematic diagram of biochemical processes which reveal the interdependence amongexergonic metabolism, protein synthesis, determination of residue sequence in protein synthesis(replication), and enzyme specificity. The vertical surface represents, generically, the enzymesof exergonic metabolism, the catalytic specificities of which are determined by amino acid se-quences established in protein synthesis. Other enzymes involved in the illustrated processes arenot indicated, but their respective catalytic specificities have a similar relationship to protein rep-lication. Establishment of amino acid sequence is shown, schematically, as the result of the se-lection of one amino acid residue, among the many available, for insertion into the polypeptideamino acid sequence at a particular point. In this illustration, arg (black arrow) is specificallyinserted at a given point in the polypeptide sequence, while other possible amino acids (ala andasp are shown as examples) are not accepted (indicated by open arrows).

tion. Replication processes are responsible for the specific synthesis of cellularenzymes, and the latter's specificity generates the catalytic effects upon which allaspects of metabolism depend. Hence, there is a circular relationship among ex-ergonic metabolism, polymer synthesis, replication, and enzyme specificity (Fig.2). Accordingly, the issue before us-analysis of the evolutionary origin of thetotal system-can be resolved in only one of two alternative ways: (i) The entirecircular system, including all of the basic functions under discussion, appearedspontaneously in the "organic soup" without any less complex precursors. (ii)The several basic processes appeared in a serial order in time; hence, at some pointin evolutionary time the functional dependencies were linear, circularity develop-ing at a later stage as a result of some refinement which rendered the initial processdependent on the last-developed one.The first of these alternatives calls for an event of enormous improbability. It

may be rejected on these grounds; in any case it is not subject to further analysis.The second alternative requires the identification of the one link, in the moderncircular relationship, which is recent and caused the conversion of the linear evolu-tionary sequence into the modern circular one (see Fig. 3).


Some observers have proposed that the linear evolution- exergonicary sequence began with replication. What is generally metabolismsuggested is that life originated when a DNA molecule, I a

with some spontaneously acquired specific nucleotide se- enzyme sytymeiquence, appeared fortuitously in the prebiotic organic solu- (gromsfs)tion, proceeded to "duplicate itself" and eventually to regu- X

determinationlate the synthesis of specific enzymes, thus generating a of monomermetabolic system.'4 This view requires the evolutionary (repqicateon)sequence shown in the right-hand panel of Figure 3.This would mean that the present mode of replication,for example, of DNA (which depends on enzyme-catalyzed FIG. 2.-Diagram to il-polymerization of adjacent nucleotides), is a recent substi- lustrate the interdepend-ency of basic processes intute for some earlier mode of replication that was independ- the modern living cell.ent of this process. In this case, in the primordial circum- An arrow is intended tosymbolize dependency;stances (in contrast with the behavior of DNA in the thus, exergonic metabol-modern cell), DNA would need to be capable of literal self- ism - polymer synthesis,

means that polymer syn-duplication, i.e., of replication unaided by any other thesis depends on exer-agencies. DNA would therefore be the only organic sub- gonic metabolism. Justi-

fication for the indicatedstance, among the myriad of possible ones, endowed with relationships is given ina capability-self-duplication-wholly unique in the realm the text.of chemistry. This is highly improbable.

In what follows I shall propose an alternative approach-that the evolutionarysequence was that shown in the left-hand part of Figure 3, and that the moderncircularity arose from the recent origin of the dependency of metabolism on specificenzymes.

This approach is derived from a consideration of the relationships between theforegoing attributes of modern living systems and an additional one-a highlyordered structure-which is equally ubiquitous in modern living cells.

Since replication involves the determination of a specific residue sequence in thesynthetic product, interest centers on the degree of precision of sequence deter-mination in in vitro and in vivo systems, for the former lack most of the structuralorganization of the living cell. The precision of in vivo protein synthesis is definedby the reproducible amino acid sequences exhibited by particular proteins, suchas enzymes. In contrast, as recently demonstrated in most detail by Grunberg-Manago and Dondon,'5 the code relations between RNA nucleotide compositionand amino acid sequence, in the incorporation of amino acids into proteins inin vitro systems, change considerably with variations in pH, Mg++ concentration,temperature, and concentration of sRNA. Apparently a "code" sufficientlyunambiguous to account for the precision of cellular protein synthesis exists onlyin the cell itself. Since the main difference between the in vivo and in vitro systemsis that the cell's highly ordered structure is absent in the artificial system, it seemsreasonable to conclude that precise determination of protein amino acid sequence,which is required for replication, depends on the pre-existence of this orderedstructure.

Similar data are available in the case of DNA replication. The data of geneticslead us to expect that in natural systems (i.e., in living cells) DNA replicationmust be quite precise, probably involving errors at a frequency which is given


met. reptic.

met. j>synth. replic. tenz. spec.

met. ¢ synth. !> replic. replic. ! enz. spec.I met.

w met. 1 synth. > replic. 0 enz. spec. replic. j enz. spec. 0 met. 0 synth.

met. met.

enz. spec. synth, enz. spec. synth.

replic. replic.

FIG. 3.-Two alternative proposals regarding the evolutionary development of the presentcircular relations among exergonic metabolism (met.), polymer synthesis (synth.), determinationof monomer sequence (replic.), and enzyme specificity (enz. spec.). In the left-hand scheme, theorigin of life begins with exergonic metabolism, the other processes being added onto the system,with time, as indicated. The final and most recent step, indicated by the black arrow, is that inwhich metabolic processes become dependent on enzymes with a specific order of residues. In theright-hand scheme, life originates with the appearance of a system (e.g., DNA) capable of inducingthe replication of its own residue sequence and that of enzyme proteins. In this scheme, themost recent step (black arrow), which establishes the modern circular relationship, is that inwhich replication, which was formerly independent of polymer (i.e., DNA) synthesis, becomesdependent on it.

roughly by the natural rate of mutation. That much more gross errors occur inin vitro systems is evident from recent studies of the DNA polymerase system.'6Hence, precise replication of DNA, which is essential to the capability of themodern cell for self-duplication, appears to be functionally dependent on the highlyorganized structure of the living cell. Such considerations, which have been dis-cussed in detail elsewhere,'3 also indicate that the biochemical specificity of DNAand of proteins has a complex origin, and that DNA is neither a "self-duplicatingmolecule" nor the sole source of the cell's inherited specificity.The relationship between exergonic metabolic processes and intracellular struc-

ture shows a striking dependency on the nature of the exergonic system. Thoseenzyme systems which are specifically associated with aerobic metabolism andwhich, on separate grounds, are known to be relatively late evolutionary develop-ments, are closely associated with complex intracellular structures. The relevantenzymes are integrated into a highly organized multimolecular unit, the mito-chondrion, and their electron carriers (e.g., the cytochrome system heme pigments)are tightly bound to their respective proteins. If this structure is disrupted, ATPformation, which is normally coupled to electron transport, does not occur. Incontrast, those electron carriers, such as DPN, that are involved in anaerobicmetabolic processes, which, as already indicated, must be regarded as more primi-tive than aerobic metabolism, are not integrated into subcellular organelles andare relatively loosely bound (having dissociation constants several orders of mag-nitude greater than those of the heme pigments) to their enzyme proteins. 17 Soluble


structureless systems of such enzymes are quite capable of ATP formation. Theserelationships support the conclusion that the origin of highly organized structures,in time, therefore lies somewhere between the development of anaerobic metabolicsystems and the systems which utilize molecular oxygen.

It is also relevant to the present considerations that the biochemical reactionsuniquely associated with aerobic metabolism are dependent on those which occuranaerobically. Thus, a product of the anaerobic oxidation of glucose, pyruvicacid, is the immediate source of the 2-carbon unit which enters into the aerobictricarboxylic acid cycle. Similarly, DPN-coupled substrate dehydrogenation is acharacteristically anaerobic process, and is also the initial step in the chain ofaerobic electron transport. This suggests an epigenetic relationship betweenanaerobic and aerobic processes; the more recent system appears to be derivedfrom, and incorporates, basic features of the more primitive one.The foregoing considerations may be summarized as follows: (i) Of the processes

under discussion, the most primitive is anaerobic metabolism. (ii) Anaerobicmetabolism, in particular the resultant formation of ATP, does not depend onhighly organized intracellular structures, while aerobic ATP formation does.(iii) On thermodynamic grounds, polymer synthesis depends on exergonic metab-olism; this relationship is generally mediated by ATP and other triphosphonucleo-tides. (iv) Precise regulation of polymer residue sequence, and therefore ofreplication, depends on the highly organized structure of the intact cell. (v) Thefirst living cells, which must have been capable of growth and replication, wereanaerobic. Hence, of the systems under consideration, aerobic metabolism ismost recent.Given these data, the following tentative order of evolutionary events can be pro-

posed; in each stage the indicated property is added to those appearing earlier, inkeeping with the principle of epigenesis:

Stage I: Anaerobic metabolism.Stage II: I + unspecific polymer synthesis (growth).Stage III: II + organized multimolecular structure.Stage IV: III + precise polymer synthesis (replication).Stage V: IV + aerobic metabolism.

The achievement of stage IV represents the origin of an organism with the fullattributes of a modern living cell: the first anaerobe. The transition betweenstages IV and V involves biological evolution and incorporates changes from thefirst anaerobe, through the emergence of photosynthesis, to aerobes.

Omitting the problem of catalysis for the moment, the biochemical events which,on the basis of data from modern organisms might have been associated with stageI, are the following (see Fig. 4): (i) An organic substrate (e.g., glucose) serves asan ultimate hydrogen donor, the ultimate hydrogen acceptor being another organicmetabolite (e.g., pyruvic acid). (ii) The foregoing over-all oxidation-reductionprocess is mediated by a hydrogen (and electron) transport agent (e.g., DPN) whichis subject to cyclic oxidation reduction, being reduced by the H-donor and re-oxidized by the H-acceptor. (iii) A nucleotide (e.g., ADP/ATP) serves as auagent of phosphate transfer; coupled to the foregoing oxidation processes, such acarrier incorporates inorganic phosphate into a terminal position in the triphospho-nucleotide (e.g., ATP). Stage II adds to the processes of stage I polymerization


STAGE 1

STAGE I

non-specific non-specificADPGDPCDP... proteins nucleic acids

p\ pyso cc ho rides

red!H-donor DPN H-acceptor

H-donor DPNHH H-occeptor~~~~ \ ~~~~~~~~~monosaccharides/ATPGTPCTP...

EXERGONIC METABOLISM NON-SPECIFIC POLYMER SYNTHESIS

(growth)

FIG. 4.-Diagram to illustrate the characteristics of stages I and II (see text) in the proposedsequence of events in the origin of life. Stage I is capable only of exergonic metabolism. Stage IIadds, to this capability, a capability for the synthesis of nonspecific polymers, i.e., polymers inwhich residue sequence is not specified, but freely variable. Stage I corresponds to the first step,in time, indicated in the left-hand scheme illustrated in Fig. 3; stage II corresponds to the secondstep in that figure.

of ATP (and other triphosphonucleotides) to form an unspecific polynucleotidepolymer, i.e., a nucleic acid of no specified nucleotide sequence.Such a system would alter the composition of the prebiotic organic solution by

reducing the concentrations of highly reduced substrates and by increasing theconcentrations of partially oxidized organic compounds and of unspecific nucleicacids. The process could go on as long as the supply of reactants lasted, but it isincapable of self-perpetuation. Unless some other events intervened, the evolu-tionary process would come to a halt, having accomplished only an irreversibletransformation of the chemical composition of the primitive "organic soup."However, the termination of this primitive system could be delayed by the in-

troduction of other polymerization processes, such as protein and polysaccharidesynthesis. The introduction of such new polymerization processes would therebyconserve the dwindling supply of reagents such as ADP and permit continuationof the basic stage II process. Such a system is capable of growth in the sense thatit would accumulate polymers, although these would be nonspecific with respectto residue sequence, at the expense of environmental reactants.

In the absence of catalysis, all of the foregoing reactions are thermodynamicallypossible and would proceed at rates determined by the respective equilibrium con-stants, concentrations, temperature, and other relevant parameters. However,certain of the reactants have a considerable absorbancy in the ultraviolet; suchradiation will raise them to excited states and may enhance the rates of reactionsini which they participate. 'Nucleotides, such as DPN and ATP, and, to a lesser


extent, aromatic amino acids, would be particularly affected. Hence, ultravioletradiation might be expected to enhance the rates of primitive redox processes andthe synthesis of polymers, especially nucleic acids. Ultraviolet radiation also tendsto degrade nucleic acids, but this effect might be minimized if these polymers, whichare relatively insoluble (especially in an acid medium) were to settle below thesurface of the aqueous system. Metals might also catalyze processes in the stageI-II system.The stage II protoorganism could accumulate a kind of protein, but since a

mechanism capable of regulating the precise sequence of amino acids in the poly-mer would be absent, such protein would lack the biochemical specificity charac-teristic of modern enzymes. However, an enzyme's catalytic activity is usuallydue to the presence of several amino acid residues in a specific geometric orienta-tion on the surface generated by the tertiary configuration which is assumed bythe protein's polypeptide chain. Extensive segments of the polypeptide chainmay often be removed without loss of enzyme activity, so long as the amino acidconfiguration around the active site is not affected. Moreover, enzymes withessentially identical catalytic activity, such as cytochromes, occurring in differentorganisms may differ significantly in their amino acid sequences. Hence, it isreasonable to expect that in primitive protein-producing systems catalytic activitymight appear in a protein as a result of the generation of a rather wide range ofamino acid sequences. In the absence of a mechanism which regulates amino acidsequence, the probability of achieving a sequence capable of rendering the proteinsomewhat active as a catalyst is much greater than that demanded by the appear-ance, de novo, of a specific sequence of several hundred residues selected from the20 alternative amino acids. Hence, with some reasonable probability we mayexpect catalytically active proteins to appear among the unspecific polypeptideswhich are characteristic of stage II protoorganisms.The appearance, among the nonspecific protein products of stage II, of enzymes

which enhance the rates of the very processes-electron transport, phosphatetransfer, and polymerization-which are necessary for protein synthesis itself,would establish a positive feedback. Such a system would be self-accelerating;and in a universe characterized by a dwindling supply of essential reagents, itwould compete successfully with other systems which had failed to generate cata-lytic proteins. This success would be reflected in an increase in the system's mass,and with fragmentation, in the number of separate units.The "organic soup" would now contain protoorganisms, capable of metabolism,

and growing in mass and number, but proliferating without retaining a highlyspecific composition or structure. These systems would exhibit a crude sort ofself-regulation, mediated by the distinctive interactions between exergonic meta-bolic processes and nucleic acid and protein synthesis. Protein synthesis, beingconnected to exergonic processes by a positive feedback, would tend to acceleratethe system's activity. In contrast, nucleic acid synthesis would tend to sequester,in a metabolically inactive form, the free nucleotides essential to exergonic metabo-lism. Since nucleic acid synthesis, in turn, depends on exergonic metabolism, theserelationships would constitute a negative feedback, in which nucleic acid syn-thesis would tend to decelerate over-all activity.As I have indicated elsewhere,'8 these relationships, nucleotide sequestration due


to DNA synthesis in particular, establish in modern organisms a system of in-heritance which appears to be responsible for the regulation of certain generalizedprocesses, such as metabolic rate and cell size. In modern organisms a system ofinheritance due to nucleotide sequestration coexists with a more precise system inwhich nucleic acids participate in the regulation of protein amino acid sequencethrough the mediation, in part, of nucleic acid templates and transfer agents. Ofthe two nucleic acid-mediated systems of inheritance, that due to nucleotidesequestration is the more primitive, being the only one present in the protoorganismsof stage II.The approximate considerations discussed earlier suggest that stage III is charac-

terized by the addition, to stage II protoorganisms, of organized multimolecularstructures such as those now found ubiquitously in modern cells. The extensivedata on cellular ultrastructure and on the compositions of proteins isolated fromvarious organisms provide specific evidence which supports this general con-clusion. These data may be generalized as follows: (i) A specific protein isolatedfrom a given species (e.g., swine insulin, horse cytochrome c) exhibits a distinctiveamino acid sequence, although the possibility of occasional departures from thissequence are suggested by data on protein microheterogeneity. (ii) Proteins withessentially identical biological activities (e.g., cytochromes) isolated from differentspecies exhibit appreciable differences in amino acid sequence. (iii) In sharp con-trast to the species-specificity of protein amino acid sequence (and by inference ofDNA nucleotide sequence), multimolecular ultrastructures observed within cellsfrom a wide range of species are remarkably similar. Electron micrographs ofmitochondria and of other intracellular structures from the cells of mammals,higher plants, and green algae are essentially indistinguishable. The 9-2 configura-tion of fibers is observed in the flagella of algae, in protozoan cilia, and in spermtails from a wide range of animals. Nevertheless, as already indicated, intra-cellular structures of different genera, however similar, are composed of proteinswhich differ significantly in amino acid sequence.

Since proteins of different amino acid sequence generate essentially identicalintracellular structures, the latter must depend on some protein properties whichare less specific than amino acid sequence (e.g., general shape and charge dis-tribution in the protein's tertiary configuration). This means that the capabilityof a protoorganism of stage II to synthesize nonspecific proteins (i.e., with variableamino acid sequences) might have sufficed to produce molecular units capable ofjoining together to form highly structured multimolecular systems. Or, viewedas a problem of relative ubiquity, we may say that the subcellular organelles, suchas ribosomes, or golgi apparatus, have a common structure among a very widerange of species, while a protein with a given amino acid sequence is much lessubiquitous. Hence, specificity of amino acid sequence represents a more recentevolutionary stage than do subcellular structures.

Thus, the relevant data reinforce the earlier conclusion that the ordered multi-molecular structure characteristic of the modern cell is an attribute which is morerecent than, and readily derived from, a system which produces unspecific proteinsand nucleic acids. This confirms the evolutionary origin of stage III. It is prob-ably significant that bacteria and blue-green algae, which are close to the start of


the sequence of biological evolution, possess relatively simple intracellular struc-tures.With the transition from stage III to stage IV, the protoorganism could acquire

the last major attribute of the modern organism-the capability for precise syn-thesis of proteins, and presumably nucleic acids, with a highly specific residuesequence. Replication and precise self-duplication would then become possible,and organisms could exhibit the types of inheritance now familiar to us.

Unfortunately, we are not yet in a position to elucidate the transition betweenstage III and IV by means of relevant biochemical data. The problem is to de-termine how a pre-existing highly organized multimolecular structure is capable ofimposing a precise ordering of residue sequence on the system's synthetic processes.That such an effect occurs is evident from modern biochemical data since, as indi-cated earlier, in vitro systems which lack this structure fail to achieve the preciseorder of residues, in both DNA and protein synthesis, that is observed in livingcells. But no explanation of this effect is now at hand.

Transferred to a test tube, the processes on the prebiotic earth would be regardedas biochemistry. And, like the biochemistry of the test tube, the biochemistry ofthe primeval earth is transformed into biology only by the subtle molecular archi-tecture that is unique to the living state. The still unsolved problem of how thecell's distinctive multimolecular structure imposes order on otherwise imprecisebiochemical reactions is, therefore, vital both for our understanding of the originof life, and for the elucidation of the most distinctive feature of the living state-self-duplication.

1 Rubey, W. W., Geol. Soc. Am., Spec. Paper, 62, 631 (1955).2Holland, H. D., in The Origin and Evolution of Atmospheres and Oceans, ed. P. J. Brancazio

and A. G. W. Cameron (New York: John Wiley, 1963).3 Berkner, L. V., and L. C. Marshall, in The Origin and Evolution of Atmospheres and Oceans,

ed. P. J. Brancazio and A. G. W. Cameron (New York: John Wiley, 1963).4Barghoorn, E. S., and S. A. Tyler, Science, 147, 563 (1965).6 Cloud, P. E., Jr., Science, 148, 27 (1965).6Oparin, A. I., The Origin of Life (New York: MacMillan, 1938).7Haldane, J. B. S., Science and Life (New York: Harper, 1933).8 Wald, G., in The Physics and Chemistry of Life (New York: Simon and Schuster, 1955).9 Blum, H. F., Time's Arrow and Evolution (New York: Harper, 1951).10Miller, S. L., in The Origin of Life on the Earth (New York: MacMillan, 1959).11 Calvin, M., in The Origin of Life on the Earth (New York: MacMillan, 1959).12Henderson, L. J., The Fitness of the Environment (New York: MacMillan, 1913).13 Commoner, B., Nature, 203, 486 (1964); Commoner, B., Am. Scientist, 52, 365 (1964).14Stanley, W. M., in The Origin of Life on the Earth (New York: MacMillan, 1959).15 Grunberg-Manago, M., and J. Dondon, Biochem. Biophys. Res. Commun., 18, 517 (1965).16Inman, R. B., C. L. Schildkraut, and A. Kornberg, J. Mul. Biol. 11, 285 (1965).17deDuve, C., R. Wattiaux, and P. Baudhuin, Advan. Enzymol., 24, 291 (1962).18 Commoner, B., Nature, 202, 960 (1964).

(Discussion ofDr. Commoner's paper)

DR. J. E. MAYER (University of California, San Diego): I would like to askDr. Commoner at what stage does he believe that right-left specificity enters theproceedings?


DR. COMMONER: Stereospecificity must have originated very early; variouspossible mechanisms which might either select or generate organic compounds withright-left specificity have been proposed, but in the absence of an establishedmechanism it is difficult to be at all precise about the time.

DR. BRITTON CHANCE (University of Pennsylvania): I understand that the key toyour hypothesis is that the modern catalyst developed last. I would like to askwhat type of catalyst you imagine to operate in the primitive anaerobic metabolismwhich is considered as the first step. It seems to me that the development ofcatalysts at this point would be essential.DR. COMMONER: Perhaps I might restate the point made in my paper as

follows: In the modern catalyst the active site represents an arrangement of onlya few amino acid residues. M\Iy proposal was that, nonspecific protein synthesisbeing already present, there might appear, with some reasonable probability,among the numerous proteins produced, a few with the surface configuration ofamino acids required for a particular catalytic effect. It is also possible that theprobability of achieving the necessary amino acid arrangement might be enhancedby coordination with a metal. Hence, catalytically active proteins might appearalthough a mechanism for ensuring a highly specific amino acid sequence wasabsent. In effect, I suggest that catalytic activity of a protein is not necessarilydependent on its total amino acid sequence, and that catalytic activity is anearlier attribute of proteins than precise amino acid sequence.DR. CLOUD: I am afraid there is not time for further discussion of this paper.

GEOCHEMIICAL ASPECTS OF ATMOSPHERIC EVOLUTION

BY CHARLES F. DAVIDSON

UNIVERSITY OF ST. ANDREWS, SCOTLAND

One of the major problems of geochemistry relates to the compositionof ancient sedimentary rocks. It can be summarized in a single simplequestion. Are these early strata isochemical with the sediments originally deposited,or have they sometimes been profoundly modified by additions and abstractions ofchemical elements during their postdepositional history? In the field of economicgeology this issue is the basis of the long-continued controversies between syngenet-icists and epigeneticists on the origin of strata-bound sulfide ore-bodies. Thesame arguments arise about the genesis of most deposits of dolomite, many kinds ofiron ore, and stratiform occurrences of barites, celestine, and other minerals.Lately, a new aspect of this old dispute has become prominent with, on one side, theisochemical school which seeks to interpret the abnormal composition of someancient sediments in terms of their deposition under an oxygen-free atmosphere, andon the other, the actualistic school which finds a uniformitarian explanation of com-positional abnormalities in the chemical effects of intrastratal waters, proof ofextraordinary atmospheres being denied.

Recent discoveries of unusual potassium-rich shales in Scotland and in Arizonapresent fresh grounds for discussions of this kind. In the Lower Cambrian fucoid

secondly, salts, - pnas · i.e., hc1, hbr,hf,etc., are gaseous, in terrestrial surroundings they...

Documents