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重建小头畸形基因的进化史,该基因控制人类脑容量。

Reconstructing the evolutionary history of microcephalin, a gene controlling human brain size.

作者信息

Evans Patrick D, Anderson Jeffrey R, Vallender Eric J, Choi Sun Shim, Lahn Bruce T

机构信息

Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.

出版信息

Hum Mol Genet. 2004 Jun 1;13(11):1139-45. doi: 10.1093/hmg/ddh126. Epub 2004 Mar 31.

Abstract

The defining process in the evolution of primates and particularly humans is the dramatic expansion of the brain. While many types of genes could potentially contribute to this process, genes that specifically regulate brain size during development may be especially relevant. Here, we examine the evolution of the microcephalin gene, whose null mutation in humans causes primary microcephaly, a congenital defect characterized by severe reductions in brain size without other gross abnormalities. We show that the evolution of microcephalin's protein sequence is highly accelerated throughout the lineage from simian ancestors to humans and chimpanzees, with the most pronounced acceleration seen in the early periods of this lineage. We further demonstrate that this accelerated evolution is coupled with signatures of positive selection. Statistical analysis suggests that about 45 advantageous amino acid changes in microcephalin might have fixed during the 25-30 million years of evolution from early simian progenitors to modern humans. These observations support the notion that the molecular evolution of microcephalin may have contributed to brain expansion in the simian lineage leading to humans. We have recently shown that ASPM, another gene linked to primary microcephaly, experienced strong positive selection in the ape lineage leading to humans. We therefore propose that genes regulating brain size during development may have the general propensity to contribute to brain evolution in primates and particularly humans.

摘要

灵长类动物尤其是人类进化过程中的决定性进程是大脑的急剧扩张。虽然许多类型的基因都可能促成这一过程,但在发育过程中专门调节脑容量的基因可能尤为重要。在此,我们研究了小头畸形基因的进化,该基因在人类中的无效突变会导致原发性小头畸形,这是一种先天性缺陷,其特征是脑容量严重减小但无其他明显异常。我们发现,从小猿祖先到人类和黑猩猩的整个谱系中,小头畸形蛋白序列的进化高度加速,在该谱系的早期阶段加速最为明显。我们进一步证明,这种加速进化与正选择的特征相关联。统计分析表明,在从早期猿类祖先到现代人类的2500万至3000万年的进化过程中,小头畸形基因可能有大约45个有利的氨基酸变化被固定下来。这些观察结果支持了这样一种观点,即小头畸形基因的分子进化可能促成了通向人类的猿类谱系中的大脑扩张。我们最近发现,另一个与原发性小头畸形相关的基因ASPM在通向人类的猿类谱系中经历了强烈的正选择。因此,我们提出,在发育过程中调节脑容量的基因可能普遍倾向于促成灵长类动物尤其是人类的大脑进化。

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