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

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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..