Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions.

Whole genome analysis in large samples from a single population is needed to provide adequate power to assess relative strengths of natural selection across different functional components of the genome. In this study, we analyzed next-generation sequencing data from 962 European Americans, and foun...

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Main Authors: Fuli Yu, Jian Lu, Xiaoming Liu, Elodie Gazave, Diana Chang, Srilakshmi Raj, Haley Hunter-Zinck, Ran Blekhman, Leonardo Arbiza, Cris Van Hout, Alanna Morrison, Andrew D Johnson, Joshua Bis, L Adrienne Cupples, Bruce M Psaty, Donna Muzny, Jin Yu, Richard A Gibbs, Alon Keinan, Andrew G Clark, Eric Boerwinkle
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0121644
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author Fuli Yu
Jian Lu
Xiaoming Liu
Elodie Gazave
Diana Chang
Srilakshmi Raj
Haley Hunter-Zinck
Ran Blekhman
Leonardo Arbiza
Cris Van Hout
Alanna Morrison
Andrew D Johnson
Joshua Bis
L Adrienne Cupples
Bruce M Psaty
Donna Muzny
Jin Yu
Richard A Gibbs
Alon Keinan
Andrew G Clark
Eric Boerwinkle
author_facet Fuli Yu
Jian Lu
Xiaoming Liu
Elodie Gazave
Diana Chang
Srilakshmi Raj
Haley Hunter-Zinck
Ran Blekhman
Leonardo Arbiza
Cris Van Hout
Alanna Morrison
Andrew D Johnson
Joshua Bis
L Adrienne Cupples
Bruce M Psaty
Donna Muzny
Jin Yu
Richard A Gibbs
Alon Keinan
Andrew G Clark
Eric Boerwinkle
author_sort Fuli Yu
collection DOAJ
description Whole genome analysis in large samples from a single population is needed to provide adequate power to assess relative strengths of natural selection across different functional components of the genome. In this study, we analyzed next-generation sequencing data from 962 European Americans, and found that as expected approximately 60% of the top 1% of positive selection signals lie in intergenic regions, 33% in intronic regions, and slightly over 1% in coding regions. Several detailed functional annotation categories in intergenic regions showed statistically significant enrichment in positively selected loci when compared to the null distribution of the genomic span of ENCODE categories. There was a significant enrichment of purifying selection signals detected in enhancers, transcription factor binding sites, microRNAs and target sites, but not on lincRNA or piRNAs, suggesting different evolutionary constraints for these domains. Loci in "repressed or low activity regions" and loci near or overlapping the transcription start site were the most significantly over-represented annotations among the top 1% of signals for positive selection.
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spelling doaj-art-82d23a2115ca48b08e1cafeb0077e3eb2025-08-20T02:09:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012164410.1371/journal.pone.0121644Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions.Fuli YuJian LuXiaoming LiuElodie GazaveDiana ChangSrilakshmi RajHaley Hunter-ZinckRan BlekhmanLeonardo ArbizaCris Van HoutAlanna MorrisonAndrew D JohnsonJoshua BisL Adrienne CupplesBruce M PsatyDonna MuznyJin YuRichard A GibbsAlon KeinanAndrew G ClarkEric BoerwinkleWhole genome analysis in large samples from a single population is needed to provide adequate power to assess relative strengths of natural selection across different functional components of the genome. In this study, we analyzed next-generation sequencing data from 962 European Americans, and found that as expected approximately 60% of the top 1% of positive selection signals lie in intergenic regions, 33% in intronic regions, and slightly over 1% in coding regions. Several detailed functional annotation categories in intergenic regions showed statistically significant enrichment in positively selected loci when compared to the null distribution of the genomic span of ENCODE categories. There was a significant enrichment of purifying selection signals detected in enhancers, transcription factor binding sites, microRNAs and target sites, but not on lincRNA or piRNAs, suggesting different evolutionary constraints for these domains. Loci in "repressed or low activity regions" and loci near or overlapping the transcription start site were the most significantly over-represented annotations among the top 1% of signals for positive selection.https://doi.org/10.1371/journal.pone.0121644
spellingShingle Fuli Yu
Jian Lu
Xiaoming Liu
Elodie Gazave
Diana Chang
Srilakshmi Raj
Haley Hunter-Zinck
Ran Blekhman
Leonardo Arbiza
Cris Van Hout
Alanna Morrison
Andrew D Johnson
Joshua Bis
L Adrienne Cupples
Bruce M Psaty
Donna Muzny
Jin Yu
Richard A Gibbs
Alon Keinan
Andrew G Clark
Eric Boerwinkle
Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions.
PLoS ONE
title Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions.
title_full Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions.
title_fullStr Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions.
title_full_unstemmed Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions.
title_short Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions.
title_sort population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non coding regions
url https://doi.org/10.1371/journal.pone.0121644
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