gene regulation in primates evolves under tissue-specific selection pressures在灵长类动物进化基因调控组织选择压力.pdfVIP

Gene Regulation in Primates Evolves under Tissue- Specific Selection Pressures 1. 2. 1 2 1 Ran Blekhman , Alicia Oshlack , Adrien E. Chabot , Gordon K. Smyth , Yoav Gilad * 1 Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America, 2 Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia 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. Citation: Blekhman R, Oshlack A, Chabot AE, Smyth GK, Gilad Y (2008) Gene Regulation in Primates Ev