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PMID: 16274263 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

PLoS biology ·Vol. 3 ·No. 12 ·2005-12-00 ·Pages e387

Rockman MV, Hahn MW, Soranzo N, Zimprich F, Goldstein DB, Wray GA

Abstract

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.

MeSH Terms
Alleles Animals Base Sequence Biomarkers Conserved Sequence Enkephalins/genetics,metabolism Evolution, Molecular Gene Expression Regulation/genetics Genetic Variation/genetics Humans Molecular Sequence Data Mutation/genetics Narcotics/metabolism Phylogeny Promoter Regions, Genetic/genetics Protein Precursors/genetics,metabolism Selection, Genetic Sequence Alignment
Chemicals
Biomarkers Enkephalins Narcotics Protein Precursors preproenkephalin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Rockman Matthew V
Department of Biology, Duke University, Durham, North Carolina, USA. [email protected]
Hahn Matthew W
Soranzo Nicole
Zimprich Fritz
Goldstein David B
Wray Gregory A
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Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
DOI
10.1371/journal.pbio.0030387
Email
[email protected]
Published
2005-12-00
Pages
e387
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC1283535
Subset
IM
Databases
GENBANK
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External Links
PubMed source DOI: 10.1371/journal.pbio.0030387 PMC Full Text View journal details
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