Rockman Matthew V, Hahn Matthew W, Soranzo Nicole, Zimprich Fritz, Goldstein David B, Wray Gregory A
Department of Biology, Duke University, Durham, North Carolina, USA.
PLoS Biol. 2005 Dec;3(12):e387. doi: 10.1371/journal.pbio.0030387.
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.
神经基因顺式调控的变化可能促成了我们物种独特属性的进化，但一直缺乏自然选择发挥作用的证据。我们发现，正向自然选择改变了人类前强啡肽原的顺式调控，前强啡肽原是一组内源性阿片肽和神经肽的前体分子，在调节感知、行为和记忆方面具有关键作用。系统发育和群体遗传学的独立证据支持了选择性清除的历史推动了人类前强啡肽原启动子的进化。在黑猩猩 - 人类杂交启动子的实验分析中，选定的序列增加了转录诱导性。大脑天然阿片类物质对诱导刺激反应发生变化的证据表明，进化过程中存在潜在的人类特异性特征。此外，现代人类群体之间和内部的连锁核苷酸和微卫星变异模式表明，在人类特异性突变固定和全球人口迁移之后，最近的选择在世界不同地区青睐了不同的前强啡肽原顺式调控等位基因。
