Abstract
Natural selection at one site shapes patterns of genetic variation at linked sites. Quantifying the effects of “linked selection” on levels of genetic diversity is key to making reliable inference about demography, building a null model in scans for targets of adaptation, and learning about the dynamics of natural selection. Here, we introduce the first method that jointly infers parameters of distinct modes of linked selection, notably background selection and selective sweeps, from genome-wide diversity data, functional annotations and genetic maps. The central idea is to calculate the probability that a neutral site is polymorphic given local annotations, substitution patterns, and recombination rates. Information is then combined across sites and samples using composite likelihood in order to estimate genome-wide parameters of distinct modes of selection. In addition to parameter estimation, this approach yields a map of the expected neutral diversity levels along the genome. To illustrate the utility of our approach, we apply it to genome-wide resequencing data from 125 lines in Drosophila melanogaster and reliably predict diversity levels at the 1Mb scale. Our results corroborate estimates of a high fraction of beneficial substitutions in proteins and untranslated regions (UTR). They allow us to distinguish between the contribution of sweeps and other modes of selection around amino acid substitutions and to uncover evidence for pervasive sweeps in untranslated regions (UTRs). Our inference further suggests a substantial effect of other modes of linked selection and of adaptation in particular. More generally, we demonstrate that linked selection has had a larger effect in reducing diversity levels and increasing their variance in D. melanogaster than previously appreciated.
Highlights
Selection at one site distorts patterns of polymorphism at linked neutral sites, acting as a local source of genetic drift
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
If linked selection introduces substantial heterogeneity in rates of coalescence along the genome, obtaining accurate estimates of demographic parameters requires a genomic map of these effects [18,19]. Such maps would serve as improved null models for other population genetic inferences, such as scans for recent targets of adaptation that rely on outlier approaches [20,21,22]
Summary
Selection at one site distorts patterns of polymorphism at linked neutral sites, acting as a local source of genetic drift. Characterizing the effects of linked selection is of central importance in many contexts. If linked selection introduces substantial heterogeneity in rates of coalescence along the genome, obtaining accurate estimates of demographic parameters requires a genomic map of these effects [18,19]. Such maps would serve as improved null models for other population genetic inferences, such as scans for recent targets of adaptation that rely on outlier approaches [20,21,22]. An accurate characterization of the effects of linked selection carries extensive information about the selective pressures that shape genome evolution. Understanding how the effects vary among taxa would inform long-standing questions about the determinants of levels of genetic diversity and genetic load within species [23,24,25, 26]
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