人类独特的大脑是人类智力产生的结构基础，人类大脑进化的遗传机制研究是解析人类大脑独特表型和人类智力起源的重要途径。通过物种间基因组的比较分析，研究人员已经找到大量人类特异的遗传变异，但是这些人类特异的遗传变异如何发挥作用，其具体的分子机制和功能后果大多都是不清楚的。在该项目中我们将从蛋白编码基因进化的角度，通过建立Mcph1人类特异位点替换小鼠模型，系统地研究人类特异的氨基酸变异和人类大脑独特表型的关系、分子机制及其功能后果。该研究的目的是为人类大脑进化提供新的遗传学证据，同时也将建立研究基因型和表型进化的实验范例。

The unique human brain is the structural basis of human intelligence, and the dissection of genetic mechanism of human brain evolution is an important way to understand the unique phenotype of human brain and the origin of human intelligence. Through comparative analysis of genomes among species, researchers have found a large number of human-specific genetic changes, however, the functional consequence of these human-specific changes remain unclear. In this project, we will systematically study the relationship, molecular mechanism and functional consequences of human-specific amino acid changes and unique human brain phenotype from the perspective of protein-coding gene evolution by establishing a Mcph1 human-specific sites replacement mouse model. The aim of the study is to provide new genetic evidence for the evolution of the human brain and to establish experimental models for studying the evolutionary pattern of genotypes and phenotypes.