Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS Biol. 2005 Dec;3(12):e387.

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

Author information

  • 1Department of Biology, Duke University, Durham, North Carolina, USA. mrockman@princeton.edu

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.

PMID:
16274263
[PubMed - indexed for MEDLINE]
PMCID:
PMC1283535
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4

Publication Types, MeSH Terms, Substances, Secondary Source ID

Publication Types

MeSH Terms

Substances

Secondary Source ID

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk