Nearly Neutral Evolution across the Drosophila melanogaster Genome.

Abstract

Under the nearly neutral theory of molecular evolution, the proportion of effectively neutral mutations is expected to depend upon the effective population size (Ne). Here, we investigate whether this is the case across the genome of Drosophila melanogaster using polymorphism data from North American and African lines. We show that the ratio of the number of nonsynonymous and synonymous polymorphisms is negatively correlated to the number of synonymous polymorphisms, even when the nonindependence is accounted for. The relationship is such that the proportion of effectively neutral nonsynonymous mutations increases by ∼45% as Ne is halved. However, we also show that this relationship is steeper than expected from an independent estimate of the distribution of fitness effects from the site frequency spectrum. We investigate a number of potential explanations for this and show, using simulation, that this is consistent with a model of genetic hitchhiking: Genetic hitchhiking depresses diversity at neutral and weakly selected sites, but has little effect on the diversity of strongly selected sites.