Effects of X-linkage and sex-biased gene expression on the rate of adaptive protein evolution in Drosophila

Abstract

Patterns of polymorphism and divergence in Drosophila protein-coding genes suggest that a considerable fraction of amino acid differences between species can be attributed to positive selection and that genes with sex-biased expression, that is, those expressed predominantly in one sex, have especially high rates of adaptive evolution. Previous studies, however, have been restricted to autosomal sex-biased genes and, thus, do not provide a complete picture of the evolutionary forces acting on sex-biased genes across the genome. To determine the effects of X-linkage on sex-biased gene evolution, we surveyed DNA sequence polymorphism and divergence in 45 X-linked genes, including 17 with male-biased expression, 13 with female-biased expression, and 15 with equal expression in the 2 sexes. Using both single- and multilocus tests for selection, we found evidence for adaptive evolution in both groups of sex-biased genes. The signal of adaptive evolution was particularly strong for X-linked male-biased genes. A comparison with data from 91 autosomal genes revealed a "fast-X" effect, in which the rate of adaptive evolution was greater for X-linked than for autosomal genes. This effect was strongest for male-biased genes but could be seen in the other groups as well. A genome-wide analysis of coding sequence divergence that accounted for sex-biased expression also uncovered a fast-X effect for male-biased and unbiased genes, suggesting that recessive beneficial mutations play an important role in adaptation.

FIG. 1.—

Maximum likelihood estimates of the fraction of positively selected amino acid replacements (α) for X-linked and autosomal genes with male-, female-, or unbiased expression using the method of Bierne and Eyre-Walker (2004). (A) Estimates of α using all polymorphic sites. (B) Estimates of α after removal of low-frequency (singleton) polymorphisms. Error bars indicate 95% CI. Asterisks indicate genes with a significant signal of positive selection. **P < 0.01, ***P < 0.001.

FIG. 2.—

Posterior distribution of the selection parameter γ for X-linked and autosomal genes with male-, female-, or unbiased expression as determined by the method of Bustamante et al. (2002). (A) Distribution of γ using all polymorphic sites. (B) Distribution of γ after removal of low-frequency (singleton) polymorphisms.

FIG. 3.—

Distribution of fitness effects for amino acid replacements in X-linked and autosomal genes with male-, female-, or unbiased expression as determined by a modified version of the method of Sawyer et al. (2007). The y axis shows the fraction of amino acid replacements with selection parameter γ greater than the value given on the x axis.

FIG. 4.—

Ratio of the adaptive substitution rate of X-linked to autosomal genes with male-, female-, or unbiased expression. The rate of adaptive substitution was defined as the number of positively selected amino acid replacements per 1000 nonsynonymous sites. Three different γ cutoffs used to define positive selection are shown on the x axis.

FIG. 5.—

Evolutionary rates of X-linked and autosomal genes with male-, female-, or unbiased expression for whole-genome comparisons of (A) Drosophila melanogaster and Drosophila simulans or (B) D. melanogaster and Drosophila yakuba. Boxes represent the interquartile range, and heavy lines indicate the median. The number of genes in each class is given above the box. Brackets indicate significant differences between X-linked and autosomal genes within a given expression class. **P < 0.01, ***P < 0.001.