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    Gene Regulation in Primates Evolves under Tissue-Specific Selection Pressures

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    Author
    Blekhman, R; Oshlack, A; Chabot, AE; Smyth, GK; Gilad, Y
    Date
    2008-11-01
    Source Title
    PLoS Genetics
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Smyth, Gordon; Oshlack, Alicia
    Affiliation
    School of Mathematics and Statistics
    School of Physics
    Metadata
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    Document Type
    Journal Article
    Citations
    Blekhman, R., Oshlack, A., Chabot, A. E., Smyth, G. K. & Gilad, Y. (2008). Gene Regulation in Primates Evolves under Tissue-Specific Selection Pressures. PLOS GENETICS, 4 (11), https://doi.org/10.1371/journal.pgen.1000271.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/259231
    DOI
    10.1371/journal.pgen.1000271
    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.

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