An Integrative Study of the Genetic and Molecular Basis of Human Brain Evolution

人脑进化的遗传和分子基础的综合研究

• 批准号: 1317195
• 负责人: Soojin Yi
• 金额: $ 30万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1317195&HistoricalAwards=false
• 关键词: Integrative; Study; Genetic; Molecular; Basis

A hallmark of human evolution is the exceptional size and complexity of our brains. Previous genetic studies have revealed that genes that are specific to human brains show particular evolutionary characteristics both at the DNA sequence and at the level of gene expression. However, the causes of such molecular changes are not known. The proposed research will investigate the molecular basis of human brain evolution using an integrative approach of genetic, epigenetic, and gene expression analyses. A central hypothesis of the proposed research is that epigenetic changes, in particular changes of DNA methylation, have facilitated the evolution of human brains. DNA methylation is a key epigenetic modification of genomic DNA that mediates information transfer between the genotype and phenotypes. The objectives of this study are first to generate DNA methylation maps of multiple humans, chimpanzees, macaques and marmosets. This novel data will be then integrated with gene expression maps of the same samples. By doing so, we can answer 1) whether DNA methylation levels exhibit a particular evolutionary trend among the primate brains examined, 2) if DNA methylation changes are correlated with gene expression changes in a species-specific manner, and 3) whether such changes are more pronounced for genes that are pertinent for the brain size and complexity. Consequently, the proposed research will elucidate the evolutionary changes and the functional consequences of DNA methylation in human brains. The proposed research is integrative in nature and will contribute to training undergraduate and graduate students in diverse disciplines including primate evolution, phylogenetics, molecular anthropology, and comparative genomics. The proposed research is integrated with an institutional outreach program, Georgia Industrial Fellowship for Teachers, to provide training for high school students and teachers in the metro Atlanta area. As a central activity of the proposed research, an open access website harboring comprehensive information on genomic, epigenomic and expression differences of the study species will be developed. Finally, the proposed research will increase our understanding of the genetic and molecular basis of the evolution of human brains, which is one of the most fascinating aspects of human evolution.

人类进化的标志是我们大脑的特殊大小和复杂性。先前的遗传研究表明，特定于人脑的基因在DNA序列和基因表达水平上都表现出特殊的进化特征。但是，这种分子变化的原因尚不清楚。拟议的研究将使用遗传，表观遗传和基因表达分析的整合方法研究人脑进化的分子基础。提出的研究的一个核心假设是，表观遗传学的变化，特别是DNA甲基化的变化，促进了人大脑的进化。 DNA甲基化是基因组DNA的关键表观遗传修饰，可介导基因型和表型之间的信息转移。 这项研究的目标首先是生成多个人类，黑猩猩，猕猴和桃花心的DNA甲基化图。然后将与同一样品的基因表达图集成此新数据。通过这样做，我们可以回答1）1）DNA甲基化水平是否在所检查的灵长类动物大脑之间表现出特殊的进化趋势，2）如果DNA甲基化变化与物种特异性方式的基因表达变化相关，并且3）3）是否对大脑大小和复杂性相关的基因更为明显。因此，拟议的研究将阐明人类大脑中DNA甲基化的进化变化和功能后果。 拟议的研究本质上是综合性的，将有助于培训各种学科的本科生和研究生，包括灵长类动物的进化，系统发育学，分子人类学和比较基因组学。拟议的研究与一项机构外展计划，佐治亚州工业奖学金的教师融合，为亚特兰大大都会地区的高中生和老师提供培训。作为拟议研究的主要活动，将开发有关研究物种的基因组，表观基因组和表达差异的全面信息的开放访问网站。最后，拟议的研究将增加我们对人大脑进化的遗传和分子基础的理解，这是人类进化最迷人的方面之一。