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Search Results: 1 - 10 of 463630 matches for " Dmitri A. Petrov "
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Evidence That Mutation Is Universally Biased towards AT in Bacteria
Ruth Hershberg ,Dmitri A. Petrov
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1001115
Abstract: Mutation is the engine that drives evolution and adaptation forward in that it generates the variation on which natural selection acts. Mutation is a random process that nevertheless occurs according to certain biases. Elucidating mutational biases and the way they vary across species and within genomes is crucial to understanding evolution and adaptation. Here we demonstrate that clonal pathogens that evolve under severely relaxed selection are uniquely suitable for studying mutational biases in bacteria. We estimate mutational patterns using sequence datasets from five such clonal pathogens belonging to four diverse bacterial clades that span most of the range of genomic nucleotide content. We demonstrate that across different types of sites and in all four clades mutation is consistently biased towards AT. This is true even in clades that have high genomic GC content. In all studied cases the mutational bias towards AT is primarily due to the high rate of C/G to T/A transitions. These results suggest that bacterial mutational biases are far less variable than previously thought. They further demonstrate that variation in nucleotide content cannot stem entirely from variation in mutational biases and that natural selection and/or a natural selection-like process such as biased gene conversion strongly affect nucleotide content.
General Rules for Optimal Codon Choice
Ruth Hershberg ,Dmitri A. Petrov
PLOS Genetics , 2009, DOI: 10.1371/journal.pgen.1000556
Abstract: Different synonymous codons are favored by natural selection for translation efficiency and accuracy in different organisms. The rules governing the identities of favored codons in different organisms remain obscure. In fact, it is not known whether such rules exist or whether favored codons are chosen randomly in evolution in a process akin to a series of frozen accidents. Here, we study this question by identifying for the first time the favored codons in 675 bacteria, 52 archea, and 10 fungi. We use a number of tests to show that the identified codons are indeed likely to be favored and find that across all studied organisms the identity of favored codons tracks the GC content of the genomes. Once the effect of the genomic GC content on selectively favored codon choice is taken into account, additional universal amino acid specific rules governing the identity of favored codons become apparent. Our results provide for the first time a clear set of rules governing the evolution of selectively favored codon usage. Based on these results, we describe a putative scenario for how evolutionary shifts in the identity of selectively favored codons can occur without even temporary weakening of natural selection for codon bias.
On the Limitations of Using Ribosomal Genes as References for the Study of Codon Usage: A Rebuttal
Ruth Hershberg, Dmitri A. Petrov
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049060
Abstract: In a recent paper published in PLOS ONE, Wang et al. challenge our finding that the identity of optimal codons in different genomes follows a set of clear rules. Here we provide a rebuttal of their paper and demonstrate that the results of our original PLOS Genetics paper stand. This provides us with an opportunity to bring up an aspect of how codon usage has been studied that should be of general interest. The Wang et al. study, as well as many other studies, used ribosomal genes as a reference set for the study of patterns of codon usage. We discuss here the assumptions that are made in order to justify using ribosomal genes to study codon bias, suggest that this practice can at times be problematic, and discuss its limitations.
Preferential Duplication of Conserved Proteins in Eukaryotic Genomes
Jerel C. Davis,Dmitri A. Petrov
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0020055
Abstract: A central goal in genome biology is to understand the origin and maintenance of genic diversity. Over evolutionary time, each gene's contribution to the genic content of an organism depends not only on its probability of long-term survival, but also on its propensity to generate duplicates that are themselves capable of long-term survival. In this study we investigate which types of genes are likely to generate functional and persistent duplicates. We demonstrate that genes that have generated duplicates in the C. elegans and S. cerevisiae genomes were 25%–50% more constrained prior to duplication than the genes that failed to leave duplicates. We further show that conserved genes have been consistently prolific in generating duplicates for hundreds of millions of years in these two species. These findings reveal one way in which gene duplication shapes the content of eukaryotic genomes. Our finding that the set of duplicate genes is biased has important implications for genome-scale studies.
Reduced selection leads to accelerated gene loss in Shigella
Ruth Hershberg, Hua Tang, Dmitri A Petrov
Genome Biology , 2007, DOI: 10.1186/gb-2007-8-8-r164
Abstract: We examined in detail the rate of gene loss in two groups of facultative pathogenic bacteria: pathogenic Escherichia coli, and Shigella. We show that Shigella strains are losing genes at an accelerated rate relative to pathogenic E. coli. We demonstrate that a genome-wide reduction in the effectiveness of selection contributes to the observed increase in the rate of gene loss in Shigella.When compared with their closely related pathogenic E. coli relatives, the more niche-limited Shigella strains appear to be losing genes at a significantly accelerated rate. A genome-wide reduction in the effectiveness of purifying selection plays a role in creating this observed difference. Our results demonstrate that differences in the effectiveness of selection contribute to differences in rate of gene loss in facultative pathogenic bacteria. We discuss how the lifestyle and pathogenicity of Shigella may alter the effectiveness of selection, thus influencing the rate of gene loss.It was long thought that mutations in the sequences of individual genes are the strongest contributors to evolutionary change. In recent years, evidence has accumulated showing that the emergence of new strains of pathogenic bacteria can be better explained by changes in the repertoire of genes through gene acquisition and gene loss [1-3]. Obligate pathogens tend to lose a very high number of genes compared with facultative pathogens, which, in turn, harbor a larger number of pseudogenes than free-living bacteria [3]. It was postulated that the observed increase in gene loss in obligate pathogens is due to two types of reduction in purifying selection [2,4-6], pathway-specific reduction and genome-wide reduction. In pathway-specific reduction, specific functions that are carried out by free-living bacteria may be provided to a certain extent by the host of the pathogenic bacteria, or may not be needed once a pathogen adapts to survival within a host. For this reason, purifying selection may be less effe
Preferential Duplication of Conserved Proteins in Eukaryotic Genomes
Jerel C Davis ,Dmitri A Petrov
PLOS Biology , 2004, DOI: 10.1371/journal.pbio.0020055
Abstract: A central goal in genome biology is to understand the origin and maintenance of genic diversity. Over evolutionary time, each gene's contribution to the genic content of an organism depends not only on its probability of long-term survival, but also on its propensity to generate duplicates that are themselves capable of long-term survival. In this study we investigate which types of genes are likely to generate functional and persistent duplicates. We demonstrate that genes that have generated duplicates in the C. elegans and S. cerevisiae genomes were 25%–50% more constrained prior to duplication than the genes that failed to leave duplicates. We further show that conserved genes have been consistently prolific in generating duplicates for hundreds of millions of years in these two species. These findings reveal one way in which gene duplication shapes the content of eukaryotic genomes. Our finding that the set of duplicate genes is biased has important implications for genome-scale studies.
Baryon resonances at large Nc, or Quark Nuclear Physics
Dmitri Diakonov,Victor Petrov,Alexey A. Vladimirov
Physics , 2012,
Abstract: We suggest a new point of view according to which baryon resonances can be understood as collective excitations about intrinsic one-quark excitations in a mean field of definite symmetry. This approach is justified in the limit of large number of colours Nc, and is similar to the physics of large-A nuclei, hence "quark nuclear physics". Although in the real world Nc is only three, we obtain a good agreement with the observed resonance spectrum of light baryons up to 2 GeV, and of lowest charmed baryon multiplets. A by-product of the scheme is the prediction of new exotic charmed (and bottom) baryons that may be stable against strong decays.
A theory of baryon resonances at large N_c
Dmitri Diakonov,Victor Petrov,Alexey A. Vladimirov
Physics , 2013, DOI: 10.1103/PhysRevD.88.074030
Abstract: At large number of colors, N_c quarks in baryons are in a mean field of definite space and flavor symmetry. We write down the general Lorentz and flavor structure of the mean field, and derive the Dirac equation for quarks in that field. The resulting baryon resonances exhibit an hierarchy of scales: The crude mass is O(N_c), the intrinsic quark excitations are O(1), and each intrinsic quark state entails a finite band of collective excitations that are split as O(1/N_c). We build a (new) theory of those collective excitations, where full dynamics is represented by only a few constants. In a limiting (but unrealistic) case when the mean field is spherically-and flavor-symmetric, our classification of resonances reduces to the SU(6) classification of the old non-relativistic quark model. Although in the real world N_c is only three, we obtain a good accordance with the observed resonance spectrum up to 2 GeV.
The McDonald-Kreitman Test and its Extensions under Frequent Adaptation: Problems and Solutions
Philipp W. Messer,Dmitri A. Petrov
Quantitative Biology , 2012, DOI: 10.1073/pnas.1220835110
Abstract: Population genomic studies have shown that genetic draft and background selection can profoundly affect the genome-wide patterns of molecular variation. We performed forward simulations under realistic gene-structure and selection scenarios to investigate whether such linkage effects impinge on the ability of the McDonald-Kreitman (MK) test to infer the rate of positive selection (\alpha) from polymorphism and divergence data. We find that in the presence of slightly deleterious mutations, MK estimates of \alpha\ severely underestimate the true rate of adaptation even if all polymorphisms with population frequencies under 50% are excluded. Furthermore, already under intermediate rates of adaptation, genetic draft substantially distorts the site frequency spectra at neutral and functional sites from the expectations under mutation-selection-drift balance. MK-type approaches that first infer demography from synonymous sites and then use the inferred demography to correct the estimation of \alpha\ obtain almost the correct \alpha\ in our simulations. However, these approaches typically infer a severe past population expansion although there was no such expansion in the simulations, casting doubt on the accuracy of methods that infer demography from synonymous polymorphism data. We suggest a simple asymptotic extension of the MK test that should yield accurate estimates of \alpha\ even in the presence of linkage effects.
Ploidy and the Predictability of Evolution in Fishers Geometric Model
Sandeep Venkataram,Diamantis Sellis,Dmitri A Petrov
Quantitative Biology , 2013,
Abstract: Predicting adaptive evolutionary trajectories is a primary goal of evolutionary biology. One can differentiate between forward and backward predictability, where forward predictability measures the likelihood of the same adaptive trajectory occurring in independent evolutions and backward predictability measures the likelihood of a particular adaptive path given the knowledge of starting and final states. Recent studies have attempted to measure both forward and backward predictability using experimental evolution in asexual haploid microorganisms. Similar experiments in diploid organisms have not been conducted. Here we simulate adaptive walks using Fisher's Geometric Model in haploids and diploids and find that adaptive walks in diploids are less forward- and more backward-predictable than adaptive walks in haploids. We argue that the difference is due to the ability of diploids in our simulations to generate transiently stable polymorphisms and to allow adaptive mutations of larger phenotypic effect. As stable polymorphisms can be generated in both haploid and diploid natural populations through a number of mechanisms, we argue that inferences based on experiments in which adaptive walks proceed through succession of monomorphic states might miss many of the key features of adaptation.
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