Shi Lei, Hu Enzhi, Wang Zhenbo, Liu Jiewei, Li Jin, Li Ming, Chen Hua, Yu Chunshui, Jiang Tianzi, Su Bing
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
Hum Genet. 2017 Feb;136(2):193-204. doi: 10.1007/s00439-016-1748-5. Epub 2016 Nov 22.
Human evolution is marked by a continued enlargement of the brain. Previous studies on human brain evolution focused on identifying sequence divergences of brain size regulating genes between humans and nonhuman primates. However, the evolutionary pattern of the brain size regulating genes during recent human evolution is largely unknown. We conducted a comprehensive analysis of the brain size regulating gene CASC5 and found that in recent human evolution, CASC5 has accumulated many modern human specific amino acid changes, including two fixed changes and six polymorphic changes. Among human populations, 4 of the 6 amino acid polymorphic sites have high frequencies of derived alleles in East Asians, but are rare in Europeans and Africans. We proved that this between-population allelic divergence was caused by regional Darwinian positive selection in East Asians. Further analysis of brain image data of Han Chinese showed significant associations of the amino acid polymorphic sites with gray matter volume. Hence, CASC5 may contribute to the morphological and structural changes of the human brain during recent evolution. The observed between-population divergence of CASC5 variants was driven by natural selection that tends to favor a larger gray matter volume in East Asians.
人类进化的标志是大脑持续增大。先前关于人类大脑进化的研究主要集中在确定人类与非人类灵长类动物之间大脑大小调节基因的序列差异。然而，在近代人类进化过程中大脑大小调节基因的进化模式在很大程度上尚不清楚。我们对大脑大小调节基因CASC5进行了全面分析，发现在近代人类进化过程中，CASC5积累了许多现代人类特有的氨基酸变化，包括两个固定变化和六个多态变化。在人类群体中，六个氨基酸多态性位点中的四个在东亚人群中具有较高频率的衍生等位基因，但在欧洲人和非洲人中很少见。我们证明这种群体间的等位基因差异是由东亚地区的达尔文正选择导致的。对汉族人群脑图像数据的进一步分析表明，氨基酸多态性位点与灰质体积存在显著关联。因此，CASC5可能在近代进化过程中对人类大脑的形态和结构变化起到了作用。观察到的CASC5变体的群体间差异是由自然选择驱动的，自然选择倾向于使东亚人的灰质体积更大。
