title: The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences.
abstract: Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research, have the largest natural geographic distribution of any nonhuman primate, and have been the focus of much evolutionary and behavioral investigation. Consequently, rhesus macaques are one of the most thoroughly studied nonhuman primate species. However, little is known about genome-wide genetic variation in this species. A detailed understanding of extant genomic variation among rhesus macaques has implications for the use of this species as a model for studies of human health and disease, as well as for evolutionary population genomics. Whole-genome sequencing analysis of 133 rhesus macaques revealed more than 43.7 million single-nucleotide variants, including thousands predicted to alter protein sequences, transcript splicing, and transcription factor binding sites. Rhesus macaques exhibit 2.5-fold higher overall nucleotide diversity and slightly elevated putative functional variation compared with humans. This functional variation in macaques provides opportunities for analyses of coding and noncoding variation, and its cellular consequences. Despite modestly higher levels of nonsynonymous variation in the macaques, the estimated distribution of fitness effects and the ratio of nonsynonymous to synonymous variants suggest that purifying selection has had stronger effects in rhesus macaques than in humans. Demographic reconstructions indicate this species has experienced a consistently large but fluctuating population size. Overall, the results presented here provide new insights into the population genomics of nonhuman primates and expand genomic information directly relevant to primate models of human disease.
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xue
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Muthuswamy
authors.initials: M
authors.lastname: Raveendran
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: R Alan
authors.initials: RA
authors.lastname: Harris
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Gloria L
authors.initials: GL
authors.lastname: Fawcett
authors.affiliation: University of Texas Health Science Center, Houston, Texas 77030, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: White
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Dahdouli
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rio Deiros
authors.affiliation: University of Texas Health Science Center, Houston, Texas 77030, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Below
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: William
authors.initials: W
authors.lastname: Salerno
authors.affiliation: Southwest National Primate Research Center, San Antonio, Texas 78227, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Cox
authors.affiliation: Department of Human Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Fan
authors.affiliation: Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
authors.forename: Betsy
authors.initials: B
authors.lastname: Ferguson
authors.affiliation: North Carolina Museum of Natural Sciences, Raleigh, North Carolina 27601, USA.|Biological and Biomedical Sciences, North Carolina Central University, Durham, North Carolina 27707, USA.|Department of Evolutionary Anthropology, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Horvath
authors.affiliation: Yerkes National Primate Research Center, Atlanta, Georgia 30322, USA.
authors.forename: Zach
authors.initials: Z
authors.lastname: Johnson
authors.affiliation: California National Primate Research Center, Davis, California 95616, USA.|School of Mathematical and Natural Sciences, Arizona State University, Phoenix, Arizona 85004, USA.
authors.forename: Sree
authors.initials: S
authors.lastname: Kanthaswamy
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: H Michael
authors.initials: HM
authors.lastname: Kubisch
authors.affiliation: Center for Stem Cell and Translational Medicine, Anhui University, Anhui, China 230601.
authors.forename: Dahai
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Duke University, Durham, North Carolina 27708, USA.|Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Platt
authors.affiliation: California National Primate Research Center, Davis, California 95616, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Smith
authors.affiliation: Center for Stem Cell and Translational Medicine, Anhui University, Anhui, China 230601.
authors.forename: Binghua
authors.initials: B
authors.lastname: Sun
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.|New England National Primate Research Center, Southborough, Massachusetts 01772, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Vallender
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin 53711, USA.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Wiseman
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Fuli
authors.initials: F
authors.lastname: Yu
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rogers
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005260:Female; D056084:Genetic Fitness; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D008253:Macaca mulatta / Q000145:classification / Q000235:genetics*; D023421:Models, Animal; D020641:Polymorphism, Single Nucleotide; D011156:Population Density; D000073336:Whole Genome Sequencing / Q000379:methods*