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Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans

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 f...

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Autores principales: Rockman, Matthew V, Hahn, Matthew W, Soranzo, Nicole, Zimprich, Fritz, Goldstein, David B, Wray, Gregory A
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1283535/
https://www.ncbi.nlm.nih.gov/pubmed/16274263
http://dx.doi.org/10.1371/journal.pbio.0030387
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author Rockman, Matthew V
Hahn, Matthew W
Soranzo, Nicole
Zimprich, Fritz
Goldstein, David B
Wray, Gregory A
author_facet Rockman, Matthew V
Hahn, Matthew W
Soranzo, Nicole
Zimprich, Fritz
Goldstein, David B
Wray, Gregory A
author_sort Rockman, Matthew V
collection PubMed
description 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.
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spelling pubmed-12835352005-11-15 Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans Rockman, Matthew V Hahn, Matthew W Soranzo, Nicole Zimprich, Fritz Goldstein, David B Wray, Gregory A PLoS Biol Research 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. Public Library of Science 2005-12 2005-11-15 /pmc/articles/PMC1283535/ /pubmed/16274263 http://dx.doi.org/10.1371/journal.pbio.0030387 Text en Copyright: © 2005 Rockman et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rockman, Matthew V
Hahn, Matthew W
Soranzo, Nicole
Zimprich, Fritz
Goldstein, David B
Wray, Gregory A
Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans
title Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans
title_full Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans
title_fullStr Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans
title_full_unstemmed Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans
title_short Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans
title_sort ancient and recent positive selection transformed opioid cis-regulation in humans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1283535/
https://www.ncbi.nlm.nih.gov/pubmed/16274263
http://dx.doi.org/10.1371/journal.pbio.0030387
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