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.
