title: Gene regulation in primates evolves under tissue-specific selection pressures.
abstract: Regulatory changes have long been hypothesized to play an important role in primate evolution. To identify adaptive regulatory changes in humans, we performed a genome-wide survey for genes in which regulation has likely evolved under natural selection. To do so, we used a multi-species microarray to measure gene expression levels in livers, kidneys, and hearts from six humans, chimpanzees, and rhesus macaques. This comparative gene expression data allowed us to identify a large number of genes, as well as specific pathways, whose inter-species expression profiles are consistent with the action of stabilizing or directional selection on gene regulation. Among the latter set, we found an enrichment of genes involved in metabolic pathways, consistent with the hypothesis that shifts in diet underlie many regulatory adaptations in humans. In addition, we found evidence for tissue-specific selection pressures, as well as lower rates of protein evolution for genes in which regulation evolves under natural selection. These observations are consistent with the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Ran
authors.initials: R
authors.lastname: Blekhman
authors.forename: Alicia
authors.initials: A
authors.lastname: Oshlack
authors.forename: Adrien E
authors.initials: AE
authors.lastname: Chabot
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Smyth
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gilad
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D002679:Pan troglodytes / Q000235:genetics; D011323:Primates / Q000235:genetics* / Q000378:metabolism; D012641:Selection, Genetic; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D014157:Transcription Factors