Doctoral Dissertation Improvement: A Genomic Analysis of Primate Orthologous Trios With Application to Craniofacial Evolution

利用遗传学的现代进步，有可能以前所未有的方式增加科学界对人类头部以及其他灵长类动物的性质、发育和形态的理解。该项目将比较来自人类的完整基因组（DNA）序列数据，以及来自黑猩猩和猕猴的新数据。韦斯和同事们从这三个物种的全基因组DNA序列中提取并比对了相同的基因。 通过搜索已知这三个序列的基因，韦斯和劳森将识别出那些在人类谱系、黑猩猩谱系和猕猴中显示出积极适应性变化证据的基因，猕猴是一个与人类和黑猩猩具有共同差异程度的物种。 人类最重要的特征之一是大脑和围绕它的头盖骨，韦斯和劳森将通过与其他两个物种的基因进行比较，识别出人类特有的这些结构的基因，并将大脑与大脑病例联系起来。 头骨包括许多完整的元素，必须作为一个整体结构进化和发展。 这种协调最可能的目标是整个发育过程及其分子相互作用。 韦斯和劳森将联合收割机DNA序列比较与蛋白质形状和相互作用数据相结合，以确定差异的总体模式。 这些结果将被用来检查颅面和大脑发育之间的相关性，使用现有的基因表达数据，该项目的智力价值包括识别基因变化，表征人类，非洲猿和旧世界猴之间的大脑和头骨的差异。 这为更详细地研究所涉及的特定基因和遗传系统提供了基础，许多其他研究人员将能够使用这一基础。 我们打算为基因和性状之间的关系的知识做出贡献，激发可以外推的假设，以提高我们对化石记录的理解，这将为重新解释以前的工作提供有价值的信息。这项研究的更广泛的影响将涉及人类学和生物信息学的几位专家之间的互动，将过去通常没有很好整合的专业之间的合作汇集在一起。 一个主要目标是建立一个多个灵长类动物相同基因的公共数据库，包括关于它们的汇总统计数据，这将是许多不同领域科学家的宝贵资源。 当然，这一主题在公众中以及广泛的科学家中具有极大的兴趣，并且非常受欢迎的媒体关注人类适应性的独特性，特别强调自然集中在头部及其奇妙的内容上，即人类大脑。

Using modern advances in genetics, it is possible to increase the scientific community's understanding of the nature, development, and morphology of the human head, as well as that of other primates, in ways not before possible. This project will compare complete genome (DNA) sequence data from humans, and new data from chimpanzees and macaques. Weiss and colleagues have extracted and aligned the same genes in these three species that were isolated from their whole-genome DNA sequences. By searching genes for which all three sequences are known, Weiss and Lawson will identify those genes that show evidence of positive adaptive change in the human lineage, in the chimpanzee lineage, and in the macaque as a species with common degrees of difference from both humans and chimpanzees. One of the most important traits in humans is the brain and the cranium that surrounds it. Weiss and Lawson will identify genes that are specific to the human form of these structures in comparison to those in the other two species, and relate the brain to the brain case. The skull includes many integrated elements and must evolve and develop as a whole integrated structure. The most likely target of this coordination are the overall developmental processes and their molecular interactions. Weiss and Lawson will combine DNA sequence comparison with protein shape and interaction data, to identify overall patterns of difference. These results will be used to examine correlations between craniofacial and brain development using available gene expression data.The intellectual merit of this project includes the identification of genetic change that characterizes the differences in the brain and skull among humans, African apes and Old World monkeys. This provides a foundation for more detailed research on specific genes and genetic systems that are involved, a foundation that many other investigators will be able to use. We intend to contribute to knowledge of the relationships between genes and traits, to stimulate hypotheses that can be extrapolated to improve our understanding of the fossil record, and this will provide information valuable for reinterpretations of previous work.The broader impact of this study will be to involve interaction among several specialists in anthropology and bioinformatics, bringing together collaborations among specialties that have generally not been well integrated in the past. A major goal is the creation of a public database of the same genes in multiple primates, including summary statistics about them, which will be a valuable resource for scientists in many different fields. Of course, this subject holds great interest in the general public, as well as to a wide range of scientists, and much highly popular media attention is given to human adaptive uniqueness, with special stress naturally focused on the head and its marvelous contents, the human brain..