Comparison of the Full Distribution of Fitness Effects of New Amino Acid Mutations Across Great Apes

Castellano, David; Macià, Moisès Coll; Tataru, Paula; Bataillon, Thomas; Munch, Kasper

doi:10.1534/genetics.119.302494

Cited by 41 publications

(56 citation statements)

References 76 publications

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“…This is consistent with the high rates of adaptive evolution observed in Drosophila (Smith & Eyre-Walker 2002;Andolfatto 2005;Eyre-Walker & Keightley 2009;Enard et al 2014) . Rates of adaptive evolution seem to be lower in humans than in Drosophila (Gossmann et al 2012;Galtier 2016;Rousselle et al 2019) which is therefore consistent with the fact that the slope is similar to the shape parameter of the gamma distribution recently estimated across great apes (Castellano et al 2019) .…”

Section: Discussionsupporting

confidence: 88%

“…Second, we find that θ N /θ NC is negatively correlated to a measure of the effective population size of a window, θ NC /d NC . We find that the slope of the relationship in a log-log scale is consistent with the estimated shape parameter of the distribution of fitness effects in great apes (assuming the distribution is gamma distributed) (Castellano et al 2019) . This is in contrast to what has been observed in Drosophila melanogaster , in which the slope of the relationship between log(θ N /θ S ) versus log(θ S ) is significantly steeper than expected given an estimate of the DFE estimated from the site frequency spectrum; a similar pattern is apparent between species (Chen et al 2017;James et al 2017) .…”

Section: Discussionsupporting

confidence: 75%

“…We find that θ N /θ NC is significantly negatively correlated to our measure of the local N e in all homininae species (Figure 3). The slope of this relationship on a log-log scale is expected to equal to the negative value of the shape parameter of the distribution of fitness effects, if the distribution is gamma distributed (Welch et al 2008 (Table 3) suggesting that, in these species, the shape of the distribution of fitness effects for new deleterious mutations is quite stable (as recently reported by (Castellano et al 2019) using the site frequency spectrum). Due to the lack of statistical power when we consider GC-conservative mutations the slope estimates become very noisy.…”

Section: Efficiency Of Negative Selectionmentioning

confidence: 54%

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Impact of mutation rate and selection at linked sites on fine-scale DNA variation across the homininae genome

Castellano

Eyre‐Walker

Munch

2018

Preprint

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DNA diversity varies across the genome of many species. Variation in diversity across a genome might arise from regional variation in the mutation rate, variation in the intensity and mode of natural selection, and regional variation in the recombination rate. We show that both non-coding and non-synonymous diversity are positively correlated to a measure of the mutation rate and the recombination rate and negatively correlated to the density of conserved sequences in 50KB windows across the genomes of humans and non-human homininae. Interestingly, we find that while non-coding diversity is equally affected by these three genomic variables, non-synonymous diversity is mostly dominated by the density of conserved sequences. The positive correlation between diversity and our measure of the mutation rate seems to be largely a direct consequence of regions with higher mutation rates having more diversity. However, the positive correlation with recombination rate and the negative correlation with the density of conserved sequences suggests that selection at linked sites also affect levels of diversity. This is supported by the observation that the ratio of the number of non-synonymous to non-coding polymorphisms is negatively correlated to a measure of the effective population size across the genome. We show these patterns persist even when we restrict our analysis to GC-conservative mutations, demonstrating that the patterns are not driven by GC biased gene conversion. In conclusion, our comparative analyses describe how recombination rate, gene density, and mutation rate interact to produce the patterns of DNA diversity that we observe along the homininae genomes.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 75%

Section: Efficiency Of Negative Selectionmentioning

confidence: 54%

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Impact of mutation rate and selection at linked sites on fine-scale DNA variation across the homininae genome

Castellano

Eyre‐Walker

Munch

2018

Preprint

Self Cite

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“…Note that this interpretation relies on the assumption that different species from a given taxonomic group share the same DFE and, in particular, the same proportion of beneficial mutations. Castellano et al [40] compared the DFE across closely related species (great apes) and found that the deleterious DFE is quite stable across great apes, comforting us in our assumption that the DFE is expected to be similar between closely related species but different between distantly related species.…”

Section: Positive Relationship Between ω a And π S Among Closely-relasupporting

confidence: 57%

Is adaptation limited by mutation? A timescale-dependent effect of genetic diversity on the adaptive substitution rate in animals

et al. 2020

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Whether adaptation is limited by the beneficial mutation supply is a long-standing question of evolutionary genetics, which is more generally related to the determination of the adaptive substitution rate and its relationship with species effective population size (N e) and genetic diversity. Empirical evidence reported so far is equivocal, with some but not all studies supporting a higher adaptive substitution rate in large-N e than in small-N e species. We gathered coding sequence polymorphism data and estimated the adaptive amino-acid substitution rate ω a , in 50 species from ten distant groups of animals with markedly different population mutation rate θ. We reveal the existence of a complex, timescale dependent relationship between species adaptive substitution rate and genetic diversity. We find a positive relationship between ω a and θ among closely related species, indicating that adaptation is indeed limited by the mutation supply, but this was only true in relatively low-θ taxa. In contrast, we uncover no significant correlation between ω a and θ at a larger taxonomic scale, suggesting that the proportion of beneficial mutations scales negatively with species' long-term N e .

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“…Moreover, a linear regression method can be used to infer the DFE from nucleotide diversity (James et al 2017). These approaches has been applied to numerous organisms, including plants (Chen et al 2017; Huber et al 2018; Chen et al 2020), Drosophila melanogaster (Keightley and Eyre-Walker 2007; Huber et al 2017; Castellano et al 2017; Barton and Zeng 2018; Johri et al 2020), and primates (Boyko et al 2008; Huber et al 2017;Kim et al 2017; Ma et al 2013; Castellano et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Inferring genome-wide correlations of mutation fitness effects between populations

Huang

Fortier

Coffman

et al. 2019

Preprint

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The effect of a mutation on fitness may differ between populations, depending on environmental and genetic context. Experimental studies have shown that such differences exist, but little is known about the broad patterns of such differences or the factors that drive them. To quantify genome-wide patterns of differences in mutation fitness effects, we extended the concept of a distribution of fitness effects (DFE) to a joint DFE between populations. To infer the joint DFE, we fit parametric models that included demographic history to genomic data summarized by the joint allele frequency spectrum. Using simulations, we showed that our approach is statistically powerful and robust to many forms of model misspecification. We then applied our approach to populations of Drosophila melanogaster, wild tomatoes, and humans. We found that mutation fitness effects are overall least correlated between populations in tomatoes and most correlated in humans, corresponding to overall genetic differentiation. In D. melanogaster and tomatoes, mutations in genes involved in immunity and stress response showed the lowest correlation of fitness effects, consistent with environmental influence. In D. melanogaster and humans, deleterious mutations showed a lower correlation of fitness effects than tolerated mutations, hinting at the complexity of the joint DFE. Together, our results show that the joint DFE can be reliably inferred and that it offers extensive insight into the genetics of population divergence. 2 mutation's effect on fitness, population genetics theory can predict a great deal; for example, how likely 3 the mutation is to be lost from or fix in the population. But population genetics theory cannot predict 4 how likely a new mutation is to have a given effect on fitness. It is known that typically the majority of 5 mutations are deleterious (reduce fitness) or nearly neutral (negligible effect on fitness), so only a small 6 minority are adaptive (increase fitness). But these three categories encompass a continuum of fitness effects. 7This continuum is quantified by the distribution of fitness effects (DFE) among new mutations (Eyre-Walker 8

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Comparison of the Full Distribution of Fitness Effects of New Amino Acid Mutations Across Great Apes

Cited by 41 publications

References 76 publications

Impact of mutation rate and selection at linked sites on fine-scale DNA variation across the homininae genome

Impact of mutation rate and selection at linked sites on fine-scale DNA variation across the homininae genome

Is adaptation limited by mutation? A timescale-dependent effect of genetic diversity on the adaptive substitution rate in animals

Inferring genome-wide correlations of mutation fitness effects between populations

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