The Interconnected Genomic and Cerebral Evolution that Shaped Human Origins

塑造人类起源的相互关联的基因组和大脑进化

• 批准号: 0318375
• 负责人: Morris Goodman
• 金额: $ 20.59万
• 依托单位: Wayne State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0318375&HistoricalAwards=false
• 关键词: Interconnected; Genomic; Cerebral; Evolution; Shaped

This research team is conducting a genome-wide search for advantageous genetic changes in humankind's ancestry. A focus is on discovering the genetic changes that shaped humankind's enlarged brain and complex cognitive abilities. The first step in the method of discovery is to identify the many thousands of genes encoding proteins that function in the cerebral cortex of humans and other catarrhine primates such as chimpanzees, gorillas, and rhesus monkeys. Next, for these cerebral cortical brain expressed genes, determine which ones show species differences in expression patterns, especially identify those genes with expression patterns that differ between humans and the other catarrhines. Finally, by data mining take full advantage not only at the completed DNA sequence of the human genome but also of the soon to be completed chimpanzee genome and, for many of the genes of interest, the growing bodies of DNA sequence data from a range of primates. With this mined sequence, data for genes of interest (those that cerebral cortical cells express) identify by phylogenetic analysis the actual mutational changes that occurred either in gene regulatory regions or in protein encoding regions and that were favored by natural selection. Results obtained so far indicate that both types of mutational changes, gene regulatory and protein-encoding, shaped the distinctive features of the human phenotype. By combining the considerable expertise of geneticists, biochemists, neuroscientists, and anthropologists, this research will bridge diverse disciplines in order to elucidate the linked genotypic-phenotypic evolution of the human brain and thereby contribute to studies that seek a fundamental understanding of human origins.This research should have broad societal impact. It will increase understanding of the genetic underpinning of the enlarged brain humans have. In doing so, it will identify those encoded proteins and DNA regulatory elements that evolved in more recent human ancestry under the force of positive selection. This information could be of great value in the field of mental health such as in the search for new therapeutic agents for mental health practitioners.

这个研究小组正在全基因组范围内寻找人类祖先中有利的基因变化。一个重点是发现基因变化，这些变化塑造了人类扩大的大脑和复杂的认知能力。发现方法的第一步是确定数千个编码蛋白质的基因，这些蛋白质在人类和其他灵长类动物（如黑猩猩、大猩猩和恒河猴）的大脑皮层中起作用。接下来，对于这些大脑皮层的大脑表达基因，确定哪些基因在表达模式上表现出物种差异，特别是识别那些在人类和其他动物之间具有不同表达模式的基因。最后，通过数据挖掘，不仅可以充分利用已完成的人类基因组DNA序列，还可以充分利用即将完成的黑猩猩基因组，对于许多感兴趣的基因，还可以充分利用来自一系列灵长类动物的不断增长的DNA序列数据。有了这个挖掘的序列，感兴趣的基因（大脑皮层细胞表达的基因）的数据通过系统发育分析确定了发生在基因调控区域或蛋白质编码区域的实际突变变化，这些变化受到自然选择的青睐。迄今为止获得的结果表明，两种类型的突变变化，基因调控和蛋白质编码，塑造了人类表型的独特特征。通过结合遗传学家、生化学家、神经科学家和人类学家的大量专业知识，这项研究将跨越不同学科，以阐明人类大脑的基因型-表型进化，从而有助于寻求对人类起源的基本理解的研究。这项研究应该具有广泛的社会影响。它将增加对人类大脑扩大的遗传基础的理解。在这样做的过程中，它将识别出那些编码的蛋白质和DNA调节元件，这些蛋白质和DNA调节元件是在正选择的力量下在更近的人类祖先中进化出来的。这些信息在精神卫生领域可能具有很大价值，例如在为精神卫生从业人员寻找新的治疗药物方面。