Estimating the Rate of Adaptive Molecular Evolution in the Presence of Slightly Deleterious Mutations and Population Size Change

Eyre‐Walker, Adam; Keightley, Peter D.

doi:10.1093/molbev/msp119

Cited by 417 publications

(745 citation statements)

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“…Note that the expected value of p in an infinite population is 6.7 Â 10 À4 for g ¼ 15 and 0.0013 for g ¼ 7.5. 2007; Boyko et al, 2008), although simulations suggest that linkage between sites may have a relatively small impact on their reliability (Eyre-Walker and Keightley, 2009). Nevertheless, these methods have limited ability to quantify the proportion of highly deleterious mutations, as well as their effects on fitness, since these mutations contribute little, if any, to observed polymorphism, and as a result, inferences of their properties are based on extrapolations of the information gathered from the more weakly selected mutations.…”

Section: Discussionmentioning

confidence: 99%

A coalescent model of background selection with recombination, demography and variation in selection coefficients

Zeng

2012

Heredity

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There is increasing evidence that background selection, the effects of the elimination of recurring deleterious mutations by natural selection on variability at linked sites, may be a major factor shaping genome-wide patterns of genetic diversity. To accurately quantify the importance of background selection, it is vital to have computationally efficient models that include essential biological features. To this end, a structured coalescent procedure is used to construct a model of background selection that takes into account the effects of recombination, recent changes in population size and variation in selection coefficients against deleterious mutations across sites. Furthermore, this model allows a flexible organization of selected and neutral sites in the region concerned, and has the ability to generate sequence variability at both selected and neutral sites, allowing the correlation between these two types of sites to be studied. The accuracy of the model is verified by checking against the results of forward simulations. These simulations also reveal several patterns of diversity that are in qualitative agreement with observations reported in recent studies of DNA sequence polymorphisms. These results suggest that the model should be useful for data analysis.

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Section: Discussionmentioning

confidence: 99%

A coalescent model of background selection with recombination, demography and variation in selection coefficients

Zeng

2012

Heredity

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“…We aim to estimate the demography, the DFE parameters and a simultaneously for each of the four wild tomato species, using the maximum likelihood method of EyreWalker and Keightley (2009). This method is available on PD Keightley's web server (http://homepages.ed.ac.uk/ eang33/) and can be summarized as follows.…”

Section: Simulation Analyses To Estimate the Dfe Parametersmentioning

confidence: 99%

“…It is also assumed that there is a class of neutral sites at which mutant alleles have no effect on fitness. For diploid organisms, the relative fitness of the wild-type genotype, heterozygous mutant and homozygous mutant genotype is 1, 1-s/2 and 1-s, respectively (Eyre-Walker and Keightley, 2009). In a second step, the rate of positively selected mutations a is estimated for coding regions.…”

Section: Simulation Analyses To Estimate the Dfe Parametersmentioning

confidence: 99%

“…Methods to measure selection, thus, attempt to estimate the past demography of species, usually based on S sites, and simultaneously or subsequently compute the effects of selection (positive or negative) on NS and NC sites (Eyre-Walker and . Such methods have so far been applied mainly to model organisms for which genome-wide polymorphism data are available (humans, Drosophila, S. cerevisiae and Arabidopsis; Wright and Andolfatto, 2008;Eyre-Walker and Keightley, 2009;Keightley and Eyre-Walker, 2010; but see Gossmann et al, 2010 andSlotte et al, 2010 for recent studies on other plant species).…”

Section: Introductionmentioning

confidence: 99%

“…As a first step, we use simulations to evaluate the robustness of the method of Eyre-Walker and Keightley (2009) for estimating the DFE parameters when only a limited set of 100-300 single-nucleotide polymorphisms (SNPs) and 40-50 sampled alleles are available (for rationale, see Materials and methods). The DFE parameters (E(s) and V(s)) can not be accurately estimated with such a low number of SNPs (Keightley and EyreWalker, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Fitness effects of derived deleterious mutations in four closely related wild tomato species with spatial structure

et al. 2011

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A key issue in evolutionary biology is an improved understanding of the genetic mechanisms by which species adapt to various environments. Using DNA sequence data, it is possible to quantify the number of adaptive and deleterious mutations, and the distribution of fitness effects of new mutations (its mean and variance) by simultaneously taking into account the demography of a given species. We investigated how selection functions at eight housekeeping genes of four closely related, outcrossing species of wild tomatoes that are native to diverse environments in western South America (Solanum arcanum, S. chilense, S. habrochaites and S. peruvianum). We found little evidence for adaptive mutations but pervasive evidence for strong purifying selection in coding regions of the four species. In contrast, the strength of purifying selection seems to vary among the four species in non-coding (NC) regions (introns). Using F ST -based measures of fixation in subdivided populations, we suggest that weak purifying selection has affected the NC regions of S. habrochaites, S. chilense and S. peruvianum. In contrast, NC regions in S. arcanum show a distribution of fitness effects with mutations being either nearly neutral or very strongly deleterious. These results suggest that closely related species with similar genetic backgrounds but experiencing contrasting environments differ in the variance of deleterious fitness effects.

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Fitness and Selection

Charlesworth¹

2013

Encyclopedia of Life Sciences

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Selection affects the genetic composition of a population through differences in fitness amongst genotypes. With discrete generations, fitnesses are usually measured relative to the value for some standard genotype because only relative fitnesses matter. For an autosomal locus with two alleles, when the highest fitness is associated with homozygotes for a particular allele, this allele will spread through the population. When the heterozygote has the highest fitness, a polymorphism is maintained by selection. Variation can also be maintained by frequency‐dependent selection, temporal and spatial variation in fitnesses and a balance between the input of deleterious mutations and their elimination by selection. Selection theory can be extended to more complex situations such as overlapping generations. Selection can act at different levels, including selection among gametes produced by the same individual or amongst groups of individuals. Selection at one site in the genome can also influence evolution and variation at linked sites. Key Concepts: Evolution by natural or artificial selection involves differences in fitnesses amongst genotypes. The fitness of a genotype measures its expected genetic contribution to the next generation. Directional selection at a single diploid genetic locus results in the replacement of one allele at the locus by the alternative allele associated with the fittest homozygote. Balancing selection, such as heterozygote advantage, results in the maintenance within a population of two or more alleles at a locus. Mutations to deleterious alleles occur throughout the genome and contribute to variability before the alleles are removed from the population by selection. Genetic drift in finite populations can cause the loss of beneficial mutations and spread of deleterious mutations. Selection can act at levels of organisation either below or above that of the individual, which may generate conflicts between its effects at different levels. Altruistic behaviour may evolve by kin or group selection. Selection at one site in the genome influences evolution and variation at sites that are genetically linked to it.

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Estimating the Rate of Adaptive Molecular Evolution in the Presence of Slightly Deleterious Mutations and Population Size Change

Cited by 417 publications

References 59 publications

A coalescent model of background selection with recombination, demography and variation in selection coefficients

A coalescent model of background selection with recombination, demography and variation in selection coefficients

Fitness effects of derived deleterious mutations in four closely related wild tomato species with spatial structure

Fitness and Selection

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