Ancient and recent positive selection transformed opioid cis-regulation in humans.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Rockman, MV; Hahn, MW; Soranzo, N; Zimprich, F; Goldstein, DB; Wray, GA
Published Date
- December 2005
Published In
Volume / Issue
- 3 / 12
Start / End Page
- e387 -
PubMed ID
- 16274263
Pubmed Central ID
- PMC1283535
Electronic International Standard Serial Number (EISSN)
- 1545-7885
International Standard Serial Number (ISSN)
- 1544-9173
Digital Object Identifier (DOI)
- 10.1371/journal.pbio.0030387
Language
- eng