The Interconnected Genomic and Cerebral Evolution that Shaped Human Origins

这个研究小组正在进行全基因组搜索，以寻找人类祖先中有利的遗传变化。 一个重点是发现基因变化，塑造了人类的大脑扩大和复杂的认知能力。 发现方法的第一步是识别编码蛋白质的数千个基因，这些蛋白质在人类和其他卡他鼻灵长类动物（如黑猩猩、大猩猩和恒河猴）的大脑皮层中起作用。 接下来，对于这些大脑皮层表达的基因，确定哪些基因在表达模式上显示出物种差异，特别是确定那些在人类和其他卡他类之间具有不同表达模式的基因。 最后，通过数据挖掘，不仅充分利用人类基因组的完整DNA序列，而且还利用即将完成的黑猩猩基因组，对于许多感兴趣的基因，来自一系列灵长类动物的DNA序列数据的增长机构。 利用这个挖掘的序列，感兴趣基因（大脑皮质细胞表达的基因）的数据通过系统发育分析来识别发生在基因调节区或蛋白质编码区中并且受到自然选择青睐的实际突变变化。 迄今为止获得的结果表明，这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、生物化学家、神经科学家和人类学家的大量专业知识，这项研究将弥合不同学科，以阐明人类大脑的相关基因型-表型进化，从而为寻求对人类起源的基本理解的研究做出贡献。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，它将识别那些编码的蛋白质和DNA调控元件，这些蛋白质和DNA调控元件在更近的人类祖先中在正选择的力量下进化而来。 这些信息在心理健康领域可能具有很大的价值，例如为心理健康从业者寻找新的治疗药物。

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.