人类大脑进化关键基因MCPH1的调控功能研究

项目名称： 人类大脑进化关键基因MCPH1的调控功能研究

项目编号： No.31301028

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 石磊

作者单位： 中国科学院昆明动物研究所

项目金额： 23万元

中文摘要： 小头症基因（MCPH1）是调控人类大脑容量的关键基因之一。在灵长类进化过程中，MCPH1受到强烈的正选择，特别是在人类进化分支中发生了快速的进化，从而可能导致MCPH1的功能分化。为了阐明MCPH1的生物学功能演化的分子机制，我们拟在MCPH1的分子进化分析的前期研究基础上，本项目重点利用细胞水平的功能验证实验，检测人与非人灵长类的MCPH1是否存在功能分化，以及人类、黑猩猩、长臂猿和猕猴等灵长类代表物种的MCPH1蛋白对下游基因调控效应的差异，检验携带人类特异突变的MCPH1基因的调控效应。旨在揭示人类大脑进化过程中，MCPH1基因的调控功能的分化，特别是在脑发育过程中，是如何通过MCPH1调控功能来达到调控神经细胞数目的。研究结果将为我们后期建立MCPH1转基因猕猴模型提供理论依据。

中文关键词： 脑容量；大脑进化；遗传；功能分化；

英文摘要： MCPH1 is one of the key genes that regulate human brain size. During primate evolution, MCPH1 has undergone strong Darwinian positive selection, especially in the lineage leading to humans, resulting in a significant protein sequence divergence between humans and nonhuman primates and possible functional changes. In this study, we aim to test this hypothesis, and we will utilize co-immunoprecipitation and reporter gene assays to examine the activating and repressing effects of MCPH1 on a set of its down-stream genes among representative primate species including human, chimpanzee, gibbon and rhesus monkey, and compare the functional outcomes of a series of mutant MCPH1 proteins which carry mutations at the human-specific sites. This study focuses on understanding the functional divergence of MCPH1 between humans and non-human primates in view of its transcriptional regulation of the down-stream genes, which may have led to a greatly enlarged neuro-progenitor pool during brain development, thus providing a potential molecular mechanism of how lineage-specific mutations of MCPH1 contributed to the enlargement of brain size during human evolution. It will provide experimental and theoretical foundations to the construction MCPH1 transgenic monkey model, and offer a new insight to a better understanding of human bra

英文关键词： Brain Size；Brain Evolution；Genetics；Functional Divergence；