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PLoS Genet. 2016 Aug 18;12(8):e1006130. doi: 10.1371/journal.pgen.1006130. eCollection 2016 Aug.

A Genomic Map of the Effects of Linked Selection in Drosophila.

Author information

1
Department of Ecology, Evolution, and Behavior, Hebrew University of Jerusalem, Jerusalem, Israel.
2
Department of Biological Sciences, Columbia University, New York, New York, United States of America.
3
Department of Ecology and Evolutionary Biology and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
4
The Laboratory of Genetics and The Integrative Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America.
5
Department of Evolution and Ecology, University of California, Davis, Davis, California, United States of America.

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.

Comment in

PMID:
27536991
PMCID:
PMC4990265
DOI:
10.1371/journal.pgen.1006130
[Indexed for MEDLINE]
Free PMC Article

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