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Cell, Vol. 85, 793798, June 14, 1996, Copyright 1996 by Cell Press

The Origin and Early Evolution Reviewof Life: Prebiotic Chemistry,the Pre-RNA World, and Time

Antonio Lazcano* and Stanley L. Miller modelsincorporate high partial pressuresof CO 2 toraisethe temperature of the Earth by a greenhouse effect*Departamento de Biolog a

Facultad de Ciencias and thus prevent the complete freezing of the oceans

(Kasting, 1993). However, a frozen Earth has some ad-Universidad Nacional Auto noma de MexicoApartado Postal 70-407 vantages for prebiotic chemistry (Bad a et al., 1994). Butagain, thereis no direct evidence either way. In addition,Cd Universitaria Mexic o 04510, D.F.

Mexico processes relevant to the origin of life may have takenplace in environments different from the terrestrial aver-Department of Chemistry and Biochemistry,

Universi ty of Cal ifornia, San Diego age, e.g ., hot springs , eutectic sea water, or drying la-goons.La Jolla, California 92093-0506

Submarine VentsShortly after the discovery of submarine vents, or hotIn the last few years,t here havebeen a number of devel-

opments in origin of life studies that merit review. We springs, at oceanic ridge crests (Corliss et al., 1979), atheory of the origin of life in these vents was proposedwill d iscuss primitive atmospheres, submarine vents,

autotrophic versus heterotrophic origin, the RNA and (Corliss et al., 1981). Considerable attention has beengiven to t his theory (Holm, 1992) and the other possiblepre-RNA worlds, and the time required for life to arise

and evolve to cyanobacteria. Topics such as prebiotic roles of vents in the origin of life, but it seems unlikelythat the vents played a role in prebiotic synthesis ofsynthesis, template polymerizations, and evolution of

specific metabolic pathways will not be discussed here. organic compounds or polymers.The hot springs arise by sea water being forced down

into the sediments for several kilometers, heated b yThe Primitive Atmospheremagma, and pushed through the vents at 350 C.A greatThere is no agreement on the composition of the primi-deal of water is involved, with the whole ocean passingtive atmosphere, with opinion varying from strongly re-through them every ten million years. The theory pro-ducing (CH 4 N2, NH3 H2O, or CO 2 H2 N2) toposes that organic synthesis took place during the p as-neutral (CO 2 N2 H2O).sage of vent water down the 350 C to 2 C gradient,There is no geological evidence either way, althoughfollowed by synthesis of peptides and other polymers,it is generally accepted that O 2 was absent. It is beyondand the conversion of these polymers to living organ-the scope of this review to explore this question, exceptisms in the temperaturegradient. The stepsin thistheoryto comment that atmospheric chemists mostly favorhave been examined and shown not to work (Miller andhigh CO 2 N2, whereas prebiotic chemists mostly favorBada, 1988). For example, organic compounds are de-more reducing conditions. Reducing c onditions are re-

composed at 350 C rather than synthesized, and poly-quired for the synthesis of amino acids, purines, pyrimi- mers such as peptides, RNA, and DNA are hydrolyzeddines,and sugars, and such syntheses are very efficientrapidly rather than synthesized at vent temperatures.(Stribling and Miller, 1987). The robustness of this typeThe submarine ventsdid play a rolein the events leadingof chemistry is supported by the occurrence of most ofto the origin of life, but this role was in regulating thethese biochemical compounds in the 4.6 10 9-year-oldcomposition of the ocean and possibly the atmosphere,Murchison meteorite, a carbonaceous chondrite, whichand, more importantly, the destruction of organic com-comes from an asteroid. The meteorite analysis resultspounds produced in the atmosphere. This means thatmake it plausible, but do not prove, that such synthesesorganic compounds would not accumulate over veryalso occurred on the primitive Earth. Based on what islong periods of time, and therefore the vent destructionknown about prebiotic chemistry, if the Earth was notsets a time frame for the origin of life of approximatelyreducing, then the organic compounds would have to beten million years (Stribling and Miller, 1987; Lazcano andbrought to it by dust particles, comets, and meteoritesMiller, 1994).(Anders, 1989; Chyba et al., 1990). The amounts that

The surprising occurrence of hyperthermophilescan be brought in this way and survive passage throughgrowing at temperatures as high as 110 C (not at 350 C)the atmosphere are quite small,and may not have beennear the vents (Forterre, 1996 [this issue of Cell]), assufficient for the origin of life.well as of tube worms and clams growing near the ventsThe temperature of the primitive Earth during the pe-at 37 C, cannot be used as an argument for the origin ofriod of the origin of life is unknown. The entire planetlife at elevated temperatures, anymore than the presentis generally thought, without direct evidence, to haveabundance of life on the Earthat 2 Cin the oceanor 37 Cremained molten for several hundred million years afterin mammals indicates an origin at these temperaturesits formation 4.6 10 9 years ago (Wetherill, 1990). The(Miller and Lazcano, 1995).oldest sedimentary rocks in the Greenland Isua for-

mation have been heated to 500 C, so the evidence onthe conditions at that t ime has largely been destroyed. Heterotrophic or Autotrophic Origins

The OparinHaldane heterotrophic theory of the originThe sediments in the Australian Warrawoona formation3.5 10 9 years old contain very convincing cyanobacte- of life has been widely accepted on the basis that a

heterotrophic organism is simpler than an autotrophicria-like microfossils (Schopf, 1993). Some atmospheric

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one, and prebiotic synthesis experiments show how There have been so many unsuccessful attempts toproduce prebiotic organic compoundsw ith CO 2 N2 H2Oeasy it is under reducing conditions to produce organic

compounds,many of whichare used in present biology. mixtures (in the absence of hydrogen) that one wonderswhether successful prebiotic synthesesare possible un-There are, however, some recent examples of autotro-

phic proposals made for a variety of reasons. der such conditions. Those who propose autotrophictheories need to provide experimental evidence of howOne reason for proposing an autotrophic origin is the

CO 2-rich model of the primitive Earths atmosphere organic compounds can be produced, and how suchsystems can work. This is quite a challenge, since even(Kasting, 1993). High pressures of CO 2 (10100 atm) im-

ply the absence of reducing conditions and organic heterotrophic entities, which need only take their com-pounds from the environment, are difficult to envision.compound synthesis, and therefore it would be neces-

saryfor the first organisms tobiosynthesizet heir organiccompounds, or to make use of the very small amounts Autotrophic Hyperthermophiles: They May

Be Ancient, but They Are Hardly Primitiveof organic compounds brought in by comets and mete-orites. Another reason for postulating an autotrophic origin of

life is that the deepest branches of the universal tree ofAn autotrophic theory involving nonenzymatic reac-tions patterned after present biochemical pathways of life are occupied by anaerobic sulfur-dependent hyper-

thermophiles that fix CO 2 by a reductive Krebs cycle. It isintermediate metabolism has been proposed (Hart-mann, 1975). According to this scheme, the citric acid then assumed that this metabolism is primordial, rather

than a result of extensive development (Maden, 1995).cycle started with acetyl-CoA by two CO 2 fixations. Thedevelopment of such a system is envisioned to require However, it is important to distinguish between ancient

and primitive. Hyperthermophiles may be cladisticallyclays, transition state metals, and UV light. Although

there are a few biosynthetic reactions that will proceed ancient, but they are hardly primitive relative to the firstliving organisms. They contain the same elaborate pro-nonenzymatically, most do not. Cyclic pathways needto be very efficient or they will stop working.An example tein biosynthesis and most of the enzymes of modern

organisms. They seem to be no more primitive in theiris the Krebs cycle, which stops unless the oxalacetatelost by nonenzymatic decarboxylation is replaced. Non- replication and translation apparatus and metabolic

abilities than mesophiles (Miller and Lazcano, 1995).cyclic pathways are less bothered by this problem, but,in any case, this idea has never been given an experi- Truly primitive organisms would be those of the RNA

world or some of their immediate descendents in whichmental test.Cairns-Smith (1982) proposed a clay mineral theory a simplified version of the DNA/protein system had al-

ready appeared. In principle, the latter could be recog-in which the genetic information is contained in the pat-tern of ions in the clay mineral lattice, and reproduction nized because they would branch off early in auniversal

tree of life, and would be endowed with simpler replica-is accomplished by crystal growth. The mineral systemis converted to the present biological oneby an unspeci- tion and translation machinery demonstrably not due to

secondary adaptations. However, no such organismsfied process called genetic takeover. There has beenno experimental support for this theory after 20 years, have been found. The study of hyperthermophiles is

an invaluable source of information on early biologicalalthough there were some promising reports that havenot been confirmed. evolution and the nature of the last common ancestor

of all extant life forms, but an extrapolation into prebioticThe most elaborate autotrophic theory is that ofWachtershauser (1992, and references therein), in which times should not be taken for granted. Since the meta-

bolic processes of the RNA world and the chemicalbiosynthesis and polymerization are postulated to takeplace on the surface of FeS and FeS 2. The reaction reactions of prebiotic times were different from present

day metabolism, phylogenetic information from extantFeS H2S FeS 2 H2 protein sequences can not be applied to understand

them.is a very favorable one ( G 9.23 kcal/mol; E

620mV at pH 7 and 25 C), so the FeS/H 2Scombination Computer Experiments on Origin of Lifeis a strong reducing agent. According to this scheme, There has been a school of workers applying computerboth enzymes and nucleic acids are the evolutionary modeling to origin of life processes (Kauffman, 1993).outcome of such surface-contained archaic metabo- These computer simulations (referred to in some circleslism. The FeS/H 2S has been used to reduce double as experiments in silico, in contrast with in vitro or inbonds, -ketoglutarate to glutamic acid, thiols to hydro- vivo) can model Darwinian evolution and the emergencecarbons, et cetera, (Hafenbradl et al., 1995, and refer- of order from chaotic systems. However, these calcula-ences therein). However, the FeS/H 2S system does not tions have so far not provided guidelines for origin ofreduceCO 2 to amino acids,purines,or pyrimidines,even life studies because they do not take into account thethough there is more than adequate free energy to do specific properties of individual organic compounds andso (Keefe et al., 1995). But the reduction of CO 2 is pre- polymers, e.g., the base pairing of AU and GC.cisely what is required of an autotrophic theory. TheFeS/H 2S system mayhavebeenused to reduce prebiotic Pre-RNA Worldscompounds synthesized by other energy sources in re- The discovery of catalytic RNA gave credibility to priorducing atmospheres, thereby being a component of a suggestions that the first living organisms were self-heterotrophic theory of the origin of life and Oparins replicatingRNAmolecules withcatalytic activity,a situa-

tion called the RNA world (Gesteland and Atkins, 1993).primitive soup.

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This idea has become widely accepted, but as will be polyphosphate mineral known, and only a few kg ofcalcium pyrophosphate have been found in a deposit inshown below, it is unlikely that RNA itself with AUGC

and a ribose phosphate backbone is a prebiotic mole- New Jersey.TheprimitiveEarth mayhave been different,but no one has yet shown how large amounts of poly-cule. We will refer to the period when the informational

macromolecule had a backbone different from ribose phosphates could have been produced. Recently, it hasbeen shown that phosphorus pentoxide (P 4O10) can bephosphate and possibly different bases as the pre-RNA

world.The pre-RNA world is assumed to have the same produced by heating volcanic basalts to 1200 C, andsmall amounts of pyrophosphate and tripolyphosphateessential characteristic of the RNA worldphenotype

and genotype both reside in the same polymer, so no have been found in a fumarole near Mount Usa in Hok-kaido, Japan (Yamagata et al., 1991). However, theprotein or related catalysts are required to be synthe-

sized. Work on nucleic acids with hexoses, instead of amounts of polyphosphates produced are so small thateven greatly increased volcanic activity on the primitivepentoses and pyranoses, in place of furanoses suggest

that a wide variety of informational macromolecules are Earth would not make polyphosphates availableas use-ful prebiotic reagents, except by their concentration inpossible, even when restricted to sugar phosphate

backbones (Eschenmoser, 1994). The most interesting very local areas. It could be argued that the first self-replicating systems arose in such rare environments.nonsugar alternative is peptide nucleic acid (PNA). This

has a backbone of ethylenediamine monoacetic acid, We consider this to be unlikely, but such a possibilitycan not be excluded altogether.with the bases attached by an acetic acid, and it binds

strongly to DNA (Nielsen, 1993). The monomers of PNA It thus follows that polyphosphates are an unlikelyprebiotic free energy source and that phosphate estersare likely prebiotic compounds, but it is not clear

whether the polymer can be formed. Since many other are unlikely to have been involved in the first genetic

material. This is a very strong statement, because of thealternatives are possible, RNA itself may have been theevolutionary outcome of a series of different genetic central role that phosphates play in the metabolism ofall known organisms, but this can only be revised whenpolymers.a robust prebiotic p rocess for polyphosphate synthesisor a plausible geochemical mechanism for concentrat-The Chemical Stability of Ribose: Implicationsing them are found. One alternative is thioesters, whichfor the Origin of Lifeare high-energy compounds (de Duve, 1991). AnotherRecent results show that RNA itself is an unlikely prebi-possibility is the spontaneous synthesis of a polymerotic molecule. The first prob lem is that there is no prebi-from high energy precursors, e.g., the polymerizationotic reaction that gives largely ribose rather than a mix-of glycine nitrile to p olyglycine is thermodynamicallyture of many sugars, including those with b ranchedfavorable, although the reaction is sluggish.chains (Shapiro, 1988), although there is one promising

prebiotic process that might be feasible using glycolal-dehyde phosphate as a starting reagent (Mu ller et al., How Long Did It Take for Life to Appear?1990). It generally has been assumed that the origin of life

The second problem is that sugars decompose verytook place after extended geological periods of time.rapidly on the geological timescale. Thus, the half-life Although it isnot possibleto assign a precisechronology

for ribose decomposition is 73 min at 100 C and pH 7, to the events leading to the origin of life, in the last fewand 44 years at 0 C and pH 7. Other sugars are similarly years estimates of the available time for this to occurunstable at 100 C and pH 7, with the rate approximately have been considerably reduced. There is compellingproportional to the amount of free aldehyde in the sugar. paleontological evidence that microbial c ommunitiesExamples are ribose 5-phosphate (t 12 9 min), deoxy- were thriving on the primitive Earth 3.5 109 years agoribose (t 12 225 min), and ribose 2,4-diphosphate (Schopf, 1993), and it has been suggested that life may(t12 31 min) (Larralde et al., 1995). have been killed off as late as 3.8 10 9 years ago if

The instability problem could be overcome if the ri- the Earth was undergoing impacts from large asteroidsbose nucleosides could have formed early, becausenu- (Maher and Stevenson, 1988; Sleep et al., 1989). Thus,cleosides are quite stable owing to the absence of free only 300 million years appear to be left for the originaldehyde in its sugar. However, there is no efficient pre- and early diversification of life.biotic synthesis of purine ribosides and no prebiotic It has been argued that such short periods of timesynthesis of pyrimidine nucleosides at all. Added to make the accumulation of the prebiotic soup unlikely,these problems is the fact that any prebiotic synthesis and therefore should be interpreted as evidence sup-of ribose or nucleosides would give a racemic mixture, porting an autotrophic origin of life (Maden, 1995). Asand all template polymerization experiments so far show argued below, there is no reason to assume that lifeenantiomeric cross inhibition. This is where the pres- required enormous periods of time to originate andence of activated L nucleosides in a template polymer- evolve to the 3.5 10 9-year-old cyanobacteria-like War-ization of activated Dnucleosides causes chain termina- rawoona microfossils. The accumulation of organiction during polymerization (Joyce et al., 1987). compounds of abiotic origin in the primitive oceans is

balanced by destructive processes, and if prebiotic syn-thesis stops because of atmospheric changes, then itAre Polyphosphates Prebiotic?

It also has become clear that polyphosphates and acti- would not be possible for life to arise after the organiccompounds decompose. On theother hand, thechemis-vated phosphates were not abundant p rebiotic com-

pounds (Keefe and Miller, 1995). There is no known try of prebiotic reactions is robust, and does not require

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extended periods of time to take place. For instance, rather unstable. Serine and threonine have half-lives ofapproximately 10 3 years at 25 C, whereas histidine andthe slow step in the Strecker synthesis of amino acids

is the hydrolysis of the corresponding amino nitrile to tyrosine decompose at a much faster rate. This problemwould have been avoided if amino acid biosynthesesthe amide, which has a half-life of 40 years at pH 8 and

0 C (Miller and Van Trump,1981)(half-lives of 40years or were accomplished by ribozymes. It has been sug-gestedthat thismaybe the case inhistidine biosynthesisa process completed in 10 5 years are slow by biological

standards, but rapid on the geological time scale). An (White, 1976), but no evidence supporting this claim isavailable.example of a relatively rapid prebiotic synthesis is that

of amino acids on the Murchison meteorite parent body,where it apparently occurred in less that 10 5 years (Pel-

The Role of Gene Duplication in Early Cell Evolutiontzeret al., 1984). Thus, although the buildup of the prebi-There is still a gap between descriptions of prebioticotic soup may have involved millions of years, the indi-events and the last common ancestor. Intermediatevidual reactions to synthesized prebiotic compoundsstages must have involved simplerorganisms withmuchhave short half-lives, and there are no known relevantsmaller genomes. The question is whether it is possibleexamples of slowly synthesized molecules.to infer some of their major characteristics. It has longWhatever the nature of the first genetic polymer, it isbeen recognized that most genetic information is notclear that hydrolysis must have limited its accumulationessential for cell growth and division. Statistical analysisin the primitive environment. An informational polymerof 80 randomly selected chromosomal loci for Bacillusmust have a lifetime comparable with that of the organ-subtilis has led to the suggestion that the minimum cellu-ism (Westheimer, 1987) or, at least, with the t ime re-lar genome size is of the order of 562 kb (Itaya, 1995).quiredfor its replication. Even if a slow addition of mono-This figure is comparable with the size of the Myco-

mers to a genetic polymer is envisioned, the rate of plasma genitalium genome, which is 580 kb long andpolymersynthesisnonetheless must be rapid comparedcodes for 482 genes (Fraser et al., 1995). The compact-with hydrolysis rates, especially if a significant amountnessof mycoplasma genomes can easily be understoodof genetic information is to be contained in the polymer.in terms of their parasitic lifestyle, but it is somewhatThus, a 100-base long RNA molecule needs to be syn-surprising that t he streamlining processes have notthesized at least 100 times faster than the hydrolysisgreatly affected the length of the genes or the numberrate of a single phosphodiester bond. Even if highlyinvolved in protein synthesis and DNA replication (Fraserstable precursors to the ribose phosphate backbone ofet al., 1995; Bork et al., 1995).RNA are proposed for the pre-RNA world, the bases

It is unlikely that such a large array of sequencesthemselves will decompose over long periods of time.involved in replication, transcription, and translationFor example, cytosine hydrolyses to uracil with a half-were already present in the first DNA/protein organisms.life of 300 years at pH 7 and 25 C in single-strandedMost enzymes are recognized to have arisen by geneDNA (Lindahl, 1993). Adenine, which is usually thoughtduplication. The uncertainty is the number of enzymesto be very stable, deaminates to hypoxanthine with athat did not arise in this manner, i.e., the starter types.half-life of 204 days at 100 C and pH 7 (Shapiro, 1995).

In some cases, the starter types may stem from slowThis is only about ten times slower than cytosinenonenzymatic reactions where the protein improves on(t12 21 days at 100 C and pH 7). Given these stabilitya previously sluggish process, e.g., pyridoxal catalyzedconstraints, there is no reason to assume that t he self-transaminations.organization of prebiotic compounds into a system

Based on the similarity of many biochemical reac-capable of undergoing Darwinian evolution involved ex-tions, and on the observation that many proteins oftended periods of time. We envision a maximum upperrelated function share the same ancestry within a givenlimit of 5 10 6 years, because this is the half-life fororganism, we estimate that the number of starter typesdestruction of organic compounds in the oceans owingranged from 20100, but the reader might want to maketo their passage through the submarine vents (Lazcanoher or his own list of minimal enzymes. Analysis of theand Miller, 1994).currently available d atabases, including the recentlyThese stability calculations can also be used to setcompleted entire genome sequences of Haemophilusan upper limit for the amount of timeavailable for proteininfluenzae (Fleischmann et al., 1995) and Mycoplasmabiosynthesis to appear. Although the emergence ofgenitalium (Fraser et al., 1995), has shown that a largetranslation was once c onsidered the central issue inproportion of each organisms genes are related to eachthe origin of life, the discovery and characterization ofother as well as to genes in distantly related species.ribozymes,including the specific binding of amino acidsAll known life forms share a common pool of highlyto RNA molecules (Yarus, 1993) and the possibility thatconserved genetic information that was shaped to apeptidyltransferase activity resides in the RNA compo-considerable extent by paralogous gene d uplicationsnent of the ribosome (Noller et al., 1992) have givenand divergence events predating the prokaryote-credence to the idea that a rudimentary form of proteineukaryote divergence.synthesis originated in the RNA world. How this took

A few examples of thewide variety of suchgene dupli-place is unknown, but it could not have been delayedcations involved in the translation and replication ma-for extendedperiodsof timeowing to the decompositionchineries include: the Escherichia coli ribosomal pro-of both RNA and amino acids in aqueous solutions,teins, which are the result of gene duplications; thewhich is significant even at low temperatures. Althoughelongation factors; aminoacyl tRNA synthetases, whichalanine decomposes slowly by irreversible decarboxyl-

ation (t 12 10 9 years at 25 C), other amino acids are are the result of gene duplication events of two major

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starter types; and DNA polymerases (cf. Lazcano and protein primitive heterotroph intoa 7,000-genesfilamen-tous cyanobacteria would require only 7 10 6 yearsMiller, 1994).

Evidence of extensive gene duplication supports the (Lazcano and Miller, 1994).It is well known that only a few weeks are required forcontention that metabolic pathways were assembled

by the so-called patchwork mechanism, i.e., original the rapid spread of duplicates in bacterial populationsunder the stress conditions of directed evolution experi-biosynthetic routes may have been mediated by primi-

tive enzymes lacking absolute substrate specificity ments. There appear to be no experimental measure-ments of the rate of formation and fixation of new(Jensen, 1976). Sequence analysis of some universally

distributed anabolic genes like those in the histidine enzyme activities resulting from gene duplication. How-ever, recent results on the organophosphate and phos-biosynthetic pathway sequencessupport this possibility

(Fani et al., 1995). In the case of chlorophyll-dependent phonate hydrolyzing phosphotriesterase from Pseu-domonas diminuta and other soil eubacteria suggestphotosynthesis, evidence of duplication and even dou-

ble-duplication events has been preserved in ferrodox- that this new enzyme diverged by duplication from the / barrel family and reached the diffusion limit in onlyins, F-type ATPases, the reductases involved in chloro-

phyll and bacteriochlorophyll biosynthesis,the bacterial 40 years (Scanlan and Reid, 1995). Thus, the rate ofduplication andfixation of new genes canbe surprisinglyphotosynthetic reaction center, the two sets of light-

harvesting antennae,and photosystems I and II(cf. Laz- fast on the geological timescale.There are a number of additional mechanisms thatcano and Miller, 1994).

could have increased the rate of metabolic evolution,including the modular assembly of new proteins, gene

Explosive Metabolic Evolution fusion events, and horizontal gene transfer as seen inIf it is assumed that life arose in a prebiotic soup con-

extensive antibiotic resistance in bacteria. Directed evo-taining most, if not all,of the necessary small molecules, lution experiments haveshown that new substrate spec-then there was a large potential energy supply available ificities appear in a few weeks from existing enzymeson the primitive Earth from different fermentations. It is by recombination events within a gene (Hall and Zuzel,clear that such compounds could provide both the 1980). This suggests that mosaic proteins may havegrowth and energy supply of a large number of organ- enhanced the catalytic repertoire of ancient organisms.isms, but this would rapidly result in the depletion of It is likely that the widespread belief that the originthe available nutrients. Although the usual example of and early evolution of life wereslow p rocesses requiringa p rimordial fermentation is that of glucose (Oparin, billions and billions of years stems from the classical1938), it is unlikely that large quantities of this sugar Darwinian approach that major changes are slow andwere available in the primitive environment because of proceed in a stepwise manner over extended periodsits instability. As noted by Clarke and Elsden (1980), of time. All the evidence reviewed here suggests thata more likely early fermentation reaction was that of stability of monomers and polymers essential for theglycine: origin of life strongly limited the possibility of a slow

emergence of life. After the explosive metabolic evolu-glycine NADH ADP P i acetate NH4 NAD ATP. tion t hat took place soon after the beginning of life, the

basic genetic processes and major molecular traits haveThe primitive ocean may have had a glycine concen- persisted essentially unchanged for more than three-

tration between 10 8 10 4 M, depending on the effi- and-a-half billion years, perhaps owing to the linkagesciency of prebiotic synthesis and whether the ultimate of the genes involved and the complex interactions be-source of organic compounds was endogenous or not. tween different metabolic routes. At a macroevolution-At one mole ATP per mole of glycine, thesevaluesc orre- ary level, this represents a case of conservatism that isspond to 10 25 10 28 cells. Such high numbers of cells even more striking than the maintenance of the majorwould lead to an exponential decrease in the concentra- animal body plans that appeared at the base of thetion of the available fermentable organic compounds of Cambrian, and which have remained basically un-prebiotic origin and would bring about a metabolic crisis changed for 600 million years.that could only be overcome by the evolutionary devel-opment of light-harvesting autotrophic organisms with ReferencesCO 2-fixing abilities (Lazcano and Miller, 1994).

Anders, E. (1989). Pre-biotic organic matter from comets and aster-The time for evolution of the first DNA/protein or-oids. Nature 342 , 255257.ganisms to oscillatorian-like cyanobacteria is usuallyAnderson, R.P., and Roth, J.R. (1977). Tandem genetic duplic ationsthought to be very long, because the latter have ratherin phage and bacteria. Annu. Rev. Microbiol. 31 , 473505.large genomes of 6 10 3 kb to 8 10 3 kb (Herdman,Bada, J.L., Bigham, C., and Miller, S.L. (1994). Impact melting of1985) and are usually considered to be very complex.frozen oceans on the early Earth: implications for t he origin of life.However, many of the evolutionary novelties required Proc. Natl. Acad. Sci. USA 91 , 12481250.

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of Life (Cambridge: Cambridge University Press).cations (Anderson and Roth, 1977), the time requiredfor the development of a 100 kb genome of a DNA/ Chyba, C.F., Thomas, P.J., Brookshaw, L., and Sagan, C. (1990).

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