Ancient and recent positive selection transformed opioid cis-regulation in humans.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Rockman, Matthew V; Hahn, Matthew W; Soranzo, Nicole; Zimprich, Fritz; Goldstein, David B; Wray, Gregory A
Year of Publication: 2005
Journal: PLoS Biol
Volume: 3
Issue: 12
Pagination: e387
Date Published: 12/2005
Publication Language: eng
ISSN: 1545-7885
Keywords: Alleles, Animals, Base Sequence, Biomarkers, Conserved Sequence, Enkephalins, Evolution, Molecular, Gene Expression Regulation, Genetic Variation, Humans, Molecular Sequence Data, Mutation, Narcotics, Phylogeny, Promoter Regions, Genetic, Protein Precursors, Selection, Genetic, Sequence Alignment

Changes in the cis-regulation of neural genes likely contributed to the evolution of our species' unique attributes, but evidence of a role for natural selection has been lacking. We found that positive natural selection altered the cis-regulation of human prodynorphin, the precursor molecule for a suite of endogenous opioids and neuropeptides with critical roles in regulating perception, behavior, and memory. Independent lines of phylogenetic and population genetic evidence support a history of selective sweeps driving the evolution of the human prodynorphin promoter. In experimental assays of chimpanzee-human hybrid promoters, the selected sequence increases transcriptional inducibility. The evidence for a change in the response of the brain's natural opioids to inductive stimuli points to potential human-specific characteristics favored during evolution. In addition, the pattern of linked nucleotide and microsatellite variation among and within modern human populations suggests that recent selection, subsequent to the fixation of the human-specific mutations and the peopling of the globe, has favored different prodynorphin cis-regulatory alleles in different parts of the world.

DOI: 10.1371/journal.pbio.0030387
Alternate Journal: PLoS Biol.
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