Abstract

<title>Author Summary</title> <p>One of the major discoveries in modern population genetics is the profound effect that natural selection on one locus can have on genetic variation patterns at linked loci. Since the first evidence for linked selection was uncovered in <italic>Drosophila melanogaster</italic> over two decades ago, substantial effort has focused on quantifying the effects and on distinguishing the relative contributions of purifying and positive selection. We introduce an approach to jointly model the effects of positive and negative selection along the genome and infer selection parameters. To this end, we consider how closely linked each neutral site is to different types of annotations and substitutions. When we apply the inference method to genome-wide data from 125 <italic>D</italic>. <italic>melanogaster</italic> lines, our model explains most of the variance in diversity levels at the megabase scale and allows us to distinguish among the contribution of different modes of selection on proteins and UTRs. More generally, we provide a map of the effects of natural selection along the genome, and show that selection at linked sites has had an even more drastic effect on diversity patterns than previously appreciated. We also make a tool available to apply this approach in other species.</p>

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