5月28日从中科院昆明动物所获悉，该所研究人员近期发现，导致人类大脑发育异常的MCPH1基因，在人类大脑进化和智力起源中起到关键作用，可能是人类大脑区别于其他非人灵长类大脑的重要遗传因素之一。相关成果在线发表于《BMC生物学》杂志。
据该所研究员宿兵介绍，人类区别于非人灵长类最显着的特征就是大容量的大脑和高度发达的认知能力。但人们缺乏对灵长类在进化过程中脑容量扩增遗传学机制的认识和理解。
“研究该问题的一个有效手段是寻找那些突变后会导致人类大脑发育异常的基因。MCPH1基因是最早被发现导致人类神经系统发育异常而引起遗传性小头症的基因。”助理研究员石磊说。
通过对MCPH1基因的蛋白序列比较分析，科研人员鉴定了一组人类和大猿特异的氨基酸突变，并对这些突变位点的功能效应进行了系统研究。他们发现，该基因中大部分的人类特异突变位点都会改变其对下游基因的调控效应。这表明MCPH1基因在人类与非人灵长类之间已经发生了明显的功能分化，并且这种功能分化可能是导致人类起源时大脑容量急剧扩增的关键动因之一。（生物谷Bioon.com）
生物谷推荐英文摘要：
BMC Biology DOI：10.1186/1741-7007-11-62
Functional divergence of the brain-size regulatinggene MCPH1 during primate evolution and theorigin of humans
Lei Shi, Ming Li, Qiang Lin, Xuebin Qi and Bing Su
Background One of the key genes that regulate human brain size, MCPH1 has evolved under strong Darwinian positive selection during the evolution of primates. During this evolution, the divergence of MCPH1 protein sequences among primates may have caused functional changes that contribute to brain enlargement. Results To test this hypothesis, we used co-immunoprecipitation and reporter gene assays to examine the activating and repressing effects of MCPH1 on a set of its down-stream genes and then compared the functional outcomes of a series of mutant MCPH1 proteins that carry mutations at the human- and great-ape-specific sites. The results demonstrate that the regulatory effects of human MCPH1 and rhesus macaque MCPH1 are different in 3 of 8 down-stream genes tested (p73, cyclinE1 and p14ARF), suggesting a functional divergence of MCPH1 between human and non-human primates. Further analyses of the mutant MCPH1 proteins indicated that most of the human-specific mutations could change the regulatory effects on the downstream genes. A similar result was also observed for one of the four great-ape-specific mutations. Conclusions Collectively, we propose that during primate evolution in general and human evolution in particular, the divergence of MCPH1 protein sequences under Darwinian positive selection led to functional modifications, providing a possible molecular mechanism of how MCPH1 contributed to brain enlargement during primate evolution and human origin.
