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

Published

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

  • 16274263

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