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Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome.

ABSTRACT: Several recent studies have estimated that a large fraction of amino acid divergence between species of Drosophila was fixed by positive selection, using statistical approaches based on the McDonald-Kreitman test. However, little is known about associated selection coefficients of beneficial amino acid mutations. Recurrent selective sweeps associated with adaptive substitutions should leave a characteristic signature in genome variability data that contains information about the frequency and strength of selection. Here, I document a significant negative correlation between the level and the frequency of synonymous site polymorphism and the rate of protein evolution in highly recombining regions of the X chromosome of D. melanogaster. This pattern is predicted by recurrent adaptive protein evolution and suggests that adaptation is an important determinant of patterns of neutral variation genome-wide. Using a maximum likelihood approach, I estimate the product of the rate and strength of selection under a recurrent genetic hitchhiking model, lambda2N(e)s approximately 3 x 10(-8). Using an approach based on the McDonald-Kreitman test, I estimate that approximately 50% of divergent amino acids were driven to fixation by positive selection, implying that beneficial amino acid substitutions are of weak effect on average, on the order of 10(-5) (i.e., 2N(e)s approximately 40). Two implications of these results are that most adaptive substitutions will be difficult to detect in genome scans of selection and that population size (and genetic drift) may be an important determinant of the evolutionary dynamics of protein adaptation.

SUBMITTER: Andolfatto P

PROVIDER: S-EPMC2099584 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome.

Andolfatto Peter P

Genome research 20071107 12

Several recent studies have estimated that a large fraction of amino acid divergence between species of Drosophila was fixed by positive selection, using statistical approaches based on the McDonald-Kreitman test. However, little is known about associated selection coefficients of beneficial amino acid mutations. Recurrent selective sweeps associated with adaptive substitutions should leave a characteristic signature in genome variability data that contains information about the frequency and st ...[more]

PMID: 17989248

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Project description:BackgroundHarnessing vast amounts of genomic data in phylogenetic context stemming from massive sequencing of multiple closely related genomes requires new tools and approaches. We present a tool for the genome-wide analysis of frequencies and patterns of amino acid substitutions in multiple alignments of genes' coding regions, and a database of amino acid substitutions in the phylogeny of 12 Drosophila genomes. We illustrate the use of these resources to address three types of evolutionary genomics questions: about fluxes in amino acid composition in proteins, about asymmetries in amino acid substitutions and about patterns of molecular evolution in duplicated genes.ResultsWe demonstrate that amino acid composition of Drosophila proteins underwent a significant shift over the last 70 million years encompassed by the studied phylogeny, with less common amino acids (Cys, Met, His) increasing in frequency and more common ones (Ala, Leu, Glu) becoming less frequent. These fluxes are strongly correlated with polarity of source and destination amino acids, resulting in overall systematic decrease of mean polarity of amino acids found in Drosophila proteins. Frequency and radicality of amino acid substitutions are higher in paralogs than in orthologous single-copy genes and are higher in gene families with paralogs than in gene families without surviving duplications. Rate and radicality of substitutions, as expected, are negatively correlated with overall level and uniformity of gene expression. However, these correlations are not observed for substitutions occurring in duplicated genes, indicating a different selective constraint on the evolution of paralogous sequences. Clades resulting from duplications show a marked asymmetry in rate and radicality of amino acid substitutions, possibly a signal of widespread neofunctionalization. These patterns differ among protein families of different functionality, with genes coding for RNA-binding proteins differing from most other functional groups in terms of amino acid substitution patterns in duplicated and single-copy genes.ConclusionsWe demonstrate that deep phylogenetic analysis of amino acid substitutions can reveal interesting genome-wide patterns. Amino acid composition of drosophilid proteins is shaped by fluxes similar to those previously observed in prokaryotic, yeast and mammalian genomes, indicating globally present patterns. Increased frequency and radicality of amino acid substitutions in duplicated genes and the presence of asymmetry of these parameters between paralogous clades indicate widespread neofunctionalization among paralogs as the mechanism of duplication retention.

Dataset Information

Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome.

Publications

Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome.

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