Differential strengths of positive selection revealed by hitchhiking effects at small physical scales in Drosophila melanogaster.

The long time scale of adaptive evolution makes it difficult to directly observe the spread of most beneficial mutations through natural populations. Therefore, inferring attributes of beneficial mutations by studying the genomic signals left by directional selection is an important component of population genetics research. One kind of signal is a trough in nearby neutral genetic variation due to selective fixation of initially rare alleles, a phenomenon known as "genetic hitchhiking." Accumulated evidence suggests that a considerable fraction of substitutions in the Drosophila genome results from positive selection, most of which are expected to have small selection coefficients and influence the population genetics of sites in the immediate vicinity. Using Drosophila melanogaster population genomic data, we found that the heterogeneity in synonymous polymorphism surrounding different categories of coding fixations is readily observable even within 25 bp of focal substitutions, which we interpret as the result of small-scale hitchhiking effects. The strength of natural selection on different sites appears to be quite heterogeneous. Particularly, neighboring fixations that changed amino acid polarities in a way that maintained the overall polarities of a protein were under stronger selection than other categories of fixations. Interestingly, we found that substitutions in slow-evolving genes are associated with stronger hitchhiking effects. This is consistent with the idea that adaptive evolution may involve few substitutions with large effects or many substitutions with small effects. Because our approach only weakly depends on the numbers of recent nonsynonymous substitutions, it can provide a complimentary view to the adaptive evolution inferred by other divergence-based evolutionary genetic methods.