Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/116425
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Type: Journal article
Title: Determining the effect of natural selection on linked neutral divergence across species
Author: Phung, T.N.
Huber, C.D.
Lohmueller, K.E.
Citation: PLoS genetics, 2016; 12(8):1-27
Publisher: Public Library of Science
Issue Date: 2016
ISSN: 1553-7390
1553-7404
Statement of
Responsibility: 
Tanya N. Phung, Christian D. Huber, Kirk E. Lohmueller
Abstract: A major goal in evolutionary biology is to understand how natural selection has shaped patterns of genetic variation across genomes. Studies in a variety of species have shown that neutral genetic diversity (intra-species differences) has been reduced at sites linked to those under direct selection. However, the effect of linked selection on neutral sequence divergence (inter-species differences) remains ambiguous. While empirical studies have reported correlations between divergence and recombination, which is interpreted as evidence for natural selection reducing linked neutral divergence, theory argues otherwise, especially for species that have diverged long ago. Here we address these outstanding issues by examining whether natural selection can affect divergence between both closely and distantly related species. We show that neutral divergence between closely related species (e.g. human-primate) is negatively correlated with functional content and positively correlated with human recombination rate. We also find that neutral divergence between distantly related species (e.g. human-rodent) is negatively correlated with functional content and positively correlated with estimates of background selection from primates. These patterns persist after accounting for the confounding factors of hypermutable CpG sites, GC content, and biased gene conversion. Coalescent models indicate that even when the contribution of ancestral polymorphism to divergence is small, background selection in the ancestral population can still explain a large proportion of the variance in divergence across the genome, generating the observed correlations. Our findings reveal that, contrary to previous intuition, natural selection can indirectly affect linked neutral divergence between both closely and distantly related species. Though we cannot formally exclude the possibility that the direct effects of purifying selection drive some of these patterns, such a scenario would be possible only if more of the genome is under purifying selection than currently believed. Our work has implications for understanding the evolution of genomes and interpreting patterns of genetic variation.
Keywords: Mammalian genomics; natural selection; gene conversion; comparative genomics; genetic polymorphism; population size; functional genomics; population genetics
Rights: © 2016 Phung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030101973
DOI: 10.1371/journal.pgen.1006199
Appears in Collections:Genetics publications

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