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Pervasive adaptive protein evolution apparent in diversity patterns around amino acid substitutions in Drosophila simulans.

Sattath S, Elyashiv E, Kolodny O, Rinott Y, Sella G - PLoS Genet. (2011)

Bottom Line: All suffer from confounding factors, however, such that the interpretation of the evidence-in particular, conclusions about the rate and strength of beneficial substitutions-remains tentative.Interestingly, it reveals two classes of beneficial fixations: a minority (approximately 3%) that appears to have had large selective effects and accounts for most of the reduction in diversity, and the remaining 10%, which seem to have had very weak selective effects.More generally, our findings provide unequivocal evidence for strongly beneficial substitutions in Drosophila and illustrate how the rapidly accumulating genome-wide data can be leveraged to address enduring questions about the genetic basis of adaptation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology, Evolution, and Behavior, Hebrew University of Jerusalem, Jerusalem, Israel.

ABSTRACT
In Drosophila, multiple lines of evidence converge in suggesting that beneficial substitutions to the genome may be common. All suffer from confounding factors, however, such that the interpretation of the evidence-in particular, conclusions about the rate and strength of beneficial substitutions-remains tentative. Here, we use genome-wide polymorphism data in D. simulans and sequenced genomes of its close relatives to construct a readily interpretable characterization of the effects of positive selection: the shape of average neutral diversity around amino acid substitutions. As expected under recurrent selective sweeps, we find a trough in diversity levels around amino acid but not around synonymous substitutions, a distinctive pattern that is not expected under alternative models. This characterization is richer than previous approaches, which relied on limited summaries of the data (e.g., the slope of a scatter plot), and relates to underlying selection parameters in a straightforward way, allowing us to make more reliable inferences about the prevalence and strength of adaptation. Specifically, we develop a coalescent-based model for the shape of the entire curve and use it to infer adaptive parameters by maximum likelihood. Our inference suggests that ∼13% of amino acid substitutions cause selective sweeps. Interestingly, it reveals two classes of beneficial fixations: a minority (approximately 3%) that appears to have had large selective effects and accounts for most of the reduction in diversity, and the remaining 10%, which seem to have had very weak selective effects. These estimates therefore help to reconcile the apparent conflict among previously published estimates of the strength of selection. More generally, our findings provide unequivocal evidence for strongly beneficial substitutions in Drosophila and illustrate how the rapidly accumulating genome-wide data can be leveraged to address enduring questions about the genetic basis of adaptation.

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The reduction in diversity around amino acid substitutions, controlling for clustering.A. The density of amino acid (red) and synonymous (black) substitutions as a function of distance from an amino acid substitution. The synonymous density was multiplied by 0.4 (the ratio of the average amino acid to the average synonymous densities) in order to make the comparison of densities more transparent. B. A comparison between the average diversity levels around amino acid (red) and synonymous substitutions (black) as a function of the density of amino acid substitutions in their vicinity. Diversity levels and density of amino acid substitutions were measured in a window size of 1kb centered at the substitution under consideration. C. The numbers of amino acid (red) and synonymous substitutions (black) used to estimate the average diversity levels at each density.
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pgen-1001302-g002: The reduction in diversity around amino acid substitutions, controlling for clustering.A. The density of amino acid (red) and synonymous (black) substitutions as a function of distance from an amino acid substitution. The synonymous density was multiplied by 0.4 (the ratio of the average amino acid to the average synonymous densities) in order to make the comparison of densities more transparent. B. A comparison between the average diversity levels around amino acid (red) and synonymous substitutions (black) as a function of the density of amino acid substitutions in their vicinity. Diversity levels and density of amino acid substitutions were measured in a window size of 1kb centered at the substitution under consideration. C. The numbers of amino acid (red) and synonymous substitutions (black) used to estimate the average diversity levels at each density.

Mentions: Our analyses also reveal that amino acid substitutions are clustered near one another (Figure 2A: red). This clustering is greater and more localized than the clustering of synonymous substitutions around amino acid substitutions (Figure 2A: black), implying that it is caused by more than the spatial distribution of exons in the genome and an elevated mutation rate near amino acid substitutions. The difference between the clustering of amino acid and synonymous substitutions further suggests that variation in constraint and possibly in adaptability among and within genes contribute to the pattern for amino acid substitutions ([33]; also see Text S1).


Pervasive adaptive protein evolution apparent in diversity patterns around amino acid substitutions in Drosophila simulans.

Sattath S, Elyashiv E, Kolodny O, Rinott Y, Sella G - PLoS Genet. (2011)

The reduction in diversity around amino acid substitutions, controlling for clustering.A. The density of amino acid (red) and synonymous (black) substitutions as a function of distance from an amino acid substitution. The synonymous density was multiplied by 0.4 (the ratio of the average amino acid to the average synonymous densities) in order to make the comparison of densities more transparent. B. A comparison between the average diversity levels around amino acid (red) and synonymous substitutions (black) as a function of the density of amino acid substitutions in their vicinity. Diversity levels and density of amino acid substitutions were measured in a window size of 1kb centered at the substitution under consideration. C. The numbers of amino acid (red) and synonymous substitutions (black) used to estimate the average diversity levels at each density.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037414&req=5

pgen-1001302-g002: The reduction in diversity around amino acid substitutions, controlling for clustering.A. The density of amino acid (red) and synonymous (black) substitutions as a function of distance from an amino acid substitution. The synonymous density was multiplied by 0.4 (the ratio of the average amino acid to the average synonymous densities) in order to make the comparison of densities more transparent. B. A comparison between the average diversity levels around amino acid (red) and synonymous substitutions (black) as a function of the density of amino acid substitutions in their vicinity. Diversity levels and density of amino acid substitutions were measured in a window size of 1kb centered at the substitution under consideration. C. The numbers of amino acid (red) and synonymous substitutions (black) used to estimate the average diversity levels at each density.
Mentions: Our analyses also reveal that amino acid substitutions are clustered near one another (Figure 2A: red). This clustering is greater and more localized than the clustering of synonymous substitutions around amino acid substitutions (Figure 2A: black), implying that it is caused by more than the spatial distribution of exons in the genome and an elevated mutation rate near amino acid substitutions. The difference between the clustering of amino acid and synonymous substitutions further suggests that variation in constraint and possibly in adaptability among and within genes contribute to the pattern for amino acid substitutions ([33]; also see Text S1).

Bottom Line: All suffer from confounding factors, however, such that the interpretation of the evidence-in particular, conclusions about the rate and strength of beneficial substitutions-remains tentative.Interestingly, it reveals two classes of beneficial fixations: a minority (approximately 3%) that appears to have had large selective effects and accounts for most of the reduction in diversity, and the remaining 10%, which seem to have had very weak selective effects.More generally, our findings provide unequivocal evidence for strongly beneficial substitutions in Drosophila and illustrate how the rapidly accumulating genome-wide data can be leveraged to address enduring questions about the genetic basis of adaptation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology, Evolution, and Behavior, Hebrew University of Jerusalem, Jerusalem, Israel.

ABSTRACT
In Drosophila, multiple lines of evidence converge in suggesting that beneficial substitutions to the genome may be common. All suffer from confounding factors, however, such that the interpretation of the evidence-in particular, conclusions about the rate and strength of beneficial substitutions-remains tentative. Here, we use genome-wide polymorphism data in D. simulans and sequenced genomes of its close relatives to construct a readily interpretable characterization of the effects of positive selection: the shape of average neutral diversity around amino acid substitutions. As expected under recurrent selective sweeps, we find a trough in diversity levels around amino acid but not around synonymous substitutions, a distinctive pattern that is not expected under alternative models. This characterization is richer than previous approaches, which relied on limited summaries of the data (e.g., the slope of a scatter plot), and relates to underlying selection parameters in a straightforward way, allowing us to make more reliable inferences about the prevalence and strength of adaptation. Specifically, we develop a coalescent-based model for the shape of the entire curve and use it to infer adaptive parameters by maximum likelihood. Our inference suggests that ∼13% of amino acid substitutions cause selective sweeps. Interestingly, it reveals two classes of beneficial fixations: a minority (approximately 3%) that appears to have had large selective effects and accounts for most of the reduction in diversity, and the remaining 10%, which seem to have had very weak selective effects. These estimates therefore help to reconcile the apparent conflict among previously published estimates of the strength of selection. More generally, our findings provide unequivocal evidence for strongly beneficial substitutions in Drosophila and illustrate how the rapidly accumulating genome-wide data can be leveraged to address enduring questions about the genetic basis of adaptation.

Show MeSH