November 18, 2005

Recent positive selection in cis-Regulation in Humans

One more paper which suggests that a locus, which shows significant differences between humans and other primates, continued to evolve after the human-specific allele was fixed. Recent selection -within the human lineage- favored different variants in Caucasoids and Asians:
Selection drove an increase in the frequency of the three-repeat allele in Europe and East Africa and independently increased the frequency of the two-repeat allele in India and China, according to the significantly reduced lnRθ values in each of the populations implicated by the FST data.
PLoS Biology Volume 3 Issue 12

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

Matthew V. Rockman et al.

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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