Nearly Neutral Evolution Across the Drosophila melanogaster Genome

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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 128 North American lines. We show that the ratio of the number of non-synonymous and synonymous polymorphisms is negatively correlated to the number of synonymous polymorphisms, even when the non-independence is accounted for. The relationship is such that the proportion of effectively neutral non-synonymous mutations increases by ~45% as Ne is halved. However, we also show that this relationship is steeper than expected from estimates 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 hitch-hiking: genetic hitch-hiking depresses diversity at neutral and weakly selected sites, but has little effect on the diversity of strongly selected sites. Thus, the rate at which the proportion of effectively neutral mutations changes with increasing Ne also depends on the factors that cause the variation in Ne.
Original languageEnglish
Publication statusPublished - 1 Nov 2017

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