Neutralism and selectionism: the molecular clock

Ayala, Francisco J.

doi:10.1016/s0378-1119(00)00479-0

Cited by 28 publications

(16 citation statements)

References 38 publications

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“…Our analyses corroborate previous conclusions concerning the irregular and contrasting patterns of evolution of GPDH and SOD (6)(7)(8). These previous studies did not take into account the phylogenetic inertia of the data in the calculation of average evolutionary rates for lineages; also, backward and parallel amino acid replacements were corrected by using the PAM algorithm of ref.…”

Section: Discussionsupporting

confidence: 90%

Erratic overdispersion of three molecular clocks: GPDH, SOD, and XDH

Rodrı́guez-Trelles

Tarrı́o

Ayala

2001

Proc. Natl. Acad. Sci. U.S.A.

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The neutrality theory predicts that the rate of neutral molecular evolution is constant over time, and thus that there is a molecular clock for timing evolutionary events. It has been observed that the variance of the rate of evolution is generally larger than expected according to the neutrality theory, which has raised the question of how reliable the molecular clock is or, indeed, whether there is a molecular clock at all. We have carried out an extensive investigation of three proteins, glycerol-3-phosphate dehydrogenase (GPDH), superoxide dismutase (SOD), and xanthine dehydrogenase (XDH). We have observed that (i) the three proteins evolve erratically through time and across lineages and (ii) the erratic patterns of acceleration and deceleration differ from locus to locus, so that one locus may evolve faster in one than another lineage, whereas the opposite may be the case for another locus. The observations are inconsistent with the predictions made by various subsidiary hypotheses proposed to account for the overdispersion of the molecular clock.T he hypothesis of the molecular clock of evolution emerged from early observations that the number of amino acid replacements in a given protein appeared to change linearly with time (1). Indeed, if proteins (and genes) evolve at constant rates they could serve as molecular clocks for timing evolutionary events and reconstructing the evolutionary history of extant species; and for delimiting the choices among mechanistic descriptions of the amino acid (and nucleotide) substitution process. A notable feature of the hypothesis of the molecular evolutionary clock is empirical multiplicity: every one of the thousands of proteins or genes of an organism would be an independent clock, each ticking at a different rate but all measuring the same events. Kimura's neutrality theory of molecular evolution provides a mathematical foundation for the clock (2, 3). The theory states that the rate of substitution, k, of adaptively neutral alleles is precisely the rate of mutation, u, of neutral alleles, k ϭ u. The neutrality theory predicts that molecular evolution behaves like a stochastic clock, such as radioactive decay, with the properties of a Poisson process; therefore, the variance of the number of substitutions, V, should be equal to the mean, M, so that the ''index of dispersion'' R ϭ V͞M ϭ 1. A common observation, however, is that genes and proteins evolve more erratically than allowed by the neutral theory (the so-called overdispersed molecular clock; refs. 4 and 5), which casts doubts on the validity of the molecular clock model (5, 6). Several subsidiary hypotheses have been proposed that modify the predictions of the neutrality theory, allowing for greater variance in evolutionary rates (6).Here we present an analysis of the rates of evolution of three genes: glycerol-3-phosphate dehydrogenase (GPDH; EC 1.1.1.8), Cu,Zn superoxide dismutase (SOD; EC 1.15.1.1), and xanthine dehydrogenase (XDH; 1.1.1.204). We have previously analyzed the evolutionary rates of GPDH and...

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Section: Discussionsupporting

confidence: 90%

Erratic overdispersion of three molecular clocks: GPDH, SOD, and XDH

Rodrı́guez-Trelles

Tarrı́o

Ayala

2001

Proc. Natl. Acad. Sci. U.S.A.

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“…As this small fraction was insuffi cient, neutralists added alleles or bases with negative selection coeffi cients to increase the fraction (1-f 0 ). The initial proposal that most of fi xated alleles or bases were produced by the cumulative process of fi xation (confused with substitution) of neutral alleles or bases by genetic drift, was changed as expressed by Ayala (2000) "a large proportion of all possible mutants are deleterious, but these are eliminated or kept at very low frequencies by natural selection with little or no consequence on the rates of molecular evolution". 3) Advantageous (positively selected) mutation may occur in a very low frequency (how low?)…”

Section: Some Necessary Previous Defi Nitions and Precisionsmentioning

confidence: 99%

“…5) Neutral evolution excludes the punctuated equilibria model (Gould and Elredge, 1977), because in stasis, gradual or nonevolutionary events are produced, but during punctuation a process of fast evolution happens. 6) Neutrality of evolution cannot be tested by the average but by the variance of the time of acquisition of taxonomic traits; in neutral evolution the mean should be equal to the variance (a Poisson distribution), but studies have revealed systematicly larger variances than means (Ayala et al, 1996;Ohta, 1992;Ohta and Gillespie, 1996;Ayala, 2000;Nei, 2005;Bedford andHartl, 2008, Nei et al, 2010). 7) Neutral (random) evolution implies full reversibility, because in a site the four bases have an equal probability to be found; the conversion of prokaryotes in eukaryotes is as probable as the inverse process.…”

Section: Phylogenies and The Molecular Clockmentioning

confidence: 99%

Foundational errors in the Neutral and Nearly-Neutral theories of evolution in relation to the Synthetic Theory: Is a new evolutionary paradigm necessary?

Valenzuela

2013

Biol. Res.

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The Neutral Theory of Evolution (NTE) proposes mutation and random genetic drift as the most important evolutionary factors. The most conspicuous feature of evolution is the genomic stability during paleontological eras and lack of variation among taxa; 98% or more of nucleotide sites are monomorphic within a species. NTE explains this homology by random fi xation of neutral bases and negative selection (purifying selection) that does not contribute either to evolution or polymorphisms. Purifying selection is insuffi cient to account for this evolutionary feature and the Nearly-Neutral Theory of Evolution (N-NTE) included negative selection with coeffi cients as low as mutation rate. These NTE and N-NTE propositions are thermodynamically (tendency to random distributions, second law), biotically (recurrent mutation), logically and mathematically (resilient equilibria instead of fi xation by drift) untenable. Recurrent forward and backward mutation and random fl uctuations of base frequencies alone in a site make life organization and fi xations impossible. Drift is not a directional evolutionary factor, but a directional tendency of matter-energy processes (second law) which threatens the biotic organization. Drift cannot drive evolution. In a site, the mutation rates among bases and selection coeffi cients determine the resilient equilibrium frequency of bases that genetic drift cannot change. The expected neutral random interaction among nucleotides is zero; however, huge interactions and periodicities were found between bases of dinucleotides separated by 1, 2… and more than 1,000 sites. Every base is coadapted with the whole genome. Neutralists found that neutral evolution is independent of population size (N); thus neutral evolution should be independent of drift, because drift eff ect is dependent upon N. Also, chromosome size and shape as well as protein size are far from random.

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“…that the substitution rates of amino acids in a given protein are fairly constant over time for different species. However, such a molecular clock was proposed to hold only when the amino acid substitutions are selectively neutral (Ayala, 2000 ;Kimura, 1983 ;Zuckerkandl & Pauling, 1965). A rationale or even a model explaining why in the case of the Dykhuizen-Hartl experiment a selection driven evolution exhibited an apparent clocklike behaviour was not given.…”

Section: Introductionmentioning

confidence: 99%

The apparent clock-like evolution of Escherichia coli in glucose-limited chemostats is reproducible at large but not at small population sizes and can be explained with Monod kinetics

2002

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To follow and model evolution of a microbial population in the chemostat, parameters are needed that give an indication of the absolute extent of evolution at a high resolution of time. In this study the evolution of the maximum specific growth rate (µ max ) and the residual glucose concentration was followed for populations of Escherichia coli K-12 under glucose-limited conditions at dilution rates of 01 h N1 , 03 h N1 and 053 h N1 during 500-700 h in continuous culture. Whereas µ max improved only during the initial 150 h, the residual glucose concentration decreased constantly during 500 h of cultivation and therefore served as a convenient parameter to monitor the evolution of a population at a high time resolution with respect to its affinity for the growthlimiting substrate. The evolution of residual glucose concentrations was reproducible in independent chemostats with a population size of 10 11 cells, whereas no reproducibility was found in chemostats containing 10 7 cells. A model based on Monod kinetics assuming successive take-overs of mutants with improved kinetic parameters (primarily K s ) was able to simulate the experimentally observed evolution of residual glucose concentrations. Similar values for the increase in glucose affinity of mutant phenotypes (K s(mutant) 06WK s(parent) ) and similar mutation rates per cell per generation leading to these mutant phenotypes (1-5W10 N7 ) were estimated in silico for all dilution rates. The model predicts a maximum rate of evolution at a dilution rate slightly below µ max /2. With increasing and decreasing dilution rates the evolution slows down, which also explains why in special cases a selectiondriven evolution can exhibit apparent clock-like behaviour. The glucose affinity for WT cells was dependent on the dilution rate with highest values at dilution rates around µ max /2. Below 03 h N1 poorer affinity was mainly due to the effects of rpoS.

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Neutralism and selectionism: the molecular clock

Cited by 28 publications

References 38 publications

Erratic overdispersion of three molecular clocks: GPDH, SOD, and XDH

Erratic overdispersion of three molecular clocks: GPDH, SOD, and XDH

Foundational errors in the Neutral and Nearly-Neutral theories of evolution in relation to the Synthetic Theory: Is a new evolutionary paradigm necessary?

The apparent clock-like evolution of Escherichia coli in glucose-limited chemostats is reproducible at large but not at small population sizes and can be explained with Monod kinetics

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