title: Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions.
abstract: 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.
authors: Human Genome Sequencing Center, Molecular and Human Genetics Department, Baylor College of Medicine, Houston, Texas, United States of America; Institute of Neurology, Tianjin Medical University General Hospital, Tianjin, China.
authors: Fuli
authors: F
authors: Yu
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, New York, United States of America; College of Life Sciences, State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors: Jian
authors: J
authors: Lu
authors: Human Genetic Center, University of Texas Health Science Center, Houston, Texas, United States of America.
authors: Xiaoming
authors: X
authors: Liu
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, New York, United States of America.
authors: Elodie
authors: E
authors: Gazave
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, New York, United States of America.
authors: Diana
authors: D
authors: Chang
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, New York, United States of America.
authors: Srilakshmi
authors: S
authors: Raj
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, New York, United States of America.
authors: Haley
authors: H
authors: Hunter-Zinck
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, New York, United States of America.
authors: Ran
authors: R
authors: Blekhman
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, New York, United States of America.
authors: Leonardo
authors: L
authors: Arbiza
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, New York, United States of America.
authors: Cris
authors: C
authors: Van Hout
authors: Human Genetic Center, University of Texas Health Science Center, Houston, Texas, United States of America.
authors: Alanna
authors: A
authors: Morrison
authors: National Heart, Lung and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts, United States of America.
authors: Andrew D
authors: AD
authors: Johnson
authors: Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington, United States of America.
authors: Joshua
authors: J
authors: Bis
authors: National Heart, Lung and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts, United States of America.
authors: L Adrienne
authors: LA
authors: Cupples
authors: Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington, United States of America.
authors: Bruce M
authors: BM
authors: Psaty
authors: Human Genome Sequencing Center, Molecular and Human Genetics Department, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Donna
authors: D
authors: Muzny
authors: Human Genome Sequencing Center, Molecular and Human Genetics Department, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Jin
authors: J
authors: Yu
authors: Human Genome Sequencing Center, Molecular and Human Genetics Department, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Richard A
authors: RA
authors: Gibbs
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, New York, United States of America.
authors: Alon
authors: A
authors: Keinan
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, New York, United States of America.
authors: Andrew G
authors: AG
authors: Clark
authors: Human Genome Sequencing Center, Molecular and Human Genetics Department, Baylor College of Medicine, Houston, Texas, United States of America; Human Genetic Center, University of Texas Health Science Center, Houston, Texas, United States of America.
authors: Eric
authors: E
authors: Boerwinkle
mesh_terms: D021901:DNA, Intergenic; D056426:Genetic Loci; D006801:Humans; D056186:Metagenomics; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide
chemical_list: D021901:DNA, Intergenic