Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.

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....

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Main Authors: Tanya N Phung, Christian D Huber, Kirk E Lohmueller
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-08-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC4980041?pdf=render
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author Tanya N Phung
Christian D Huber
Kirk E Lohmueller
author_facet Tanya N Phung
Christian D Huber
Kirk E Lohmueller
author_sort Tanya N Phung
collection DOAJ
description 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.
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spelling doaj.art-31f6deb03bed482d9a03f228a35aba352022-12-22T00:52:53ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-08-01128e100619910.1371/journal.pgen.1006199Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.Tanya N PhungChristian D HuberKirk E LohmuellerA 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.http://europepmc.org/articles/PMC4980041?pdf=render
spellingShingle Tanya N Phung
Christian D Huber
Kirk E Lohmueller
Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.
PLoS Genetics
title Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.
title_full Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.
title_fullStr Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.
title_full_unstemmed Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.
title_short Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.
title_sort determining the effect of natural selection on linked neutral divergence across species
url http://europepmc.org/articles/PMC4980041?pdf=render
work_keys_str_mv AT tanyanphung determiningtheeffectofnaturalselectiononlinkedneutraldivergenceacrossspecies
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AT kirkelohmueller determiningtheeffectofnaturalselectiononlinkedneutraldivergenceacrossspecies