I propose to take first steps towards understanding the evolutionary processes that shape gene regulation in primates, and in particular, to study the mechanisms of regulatory change in humans and our close evolutionary relatives. By using RNA sequencing, I propose to study and compare gene expression phenotypes in multiple tissues and across species at unprecedented resolution, as well as to characterize exon usage and alternative splicing patterns. Subsequently, by using a combination of genomic approaches that will allow me to characterize histone modification marks and methylation profiles at genome-wide scale, I propose to move beyond simple inter-species comparisons of gene expression levels to the study of underlying regulatory mechanisms such as chromatin state and epigenetic markers.
At the conclusion of this work I will have high-resolution gene expression data, methylation state, and histone modification profiles from a set of five tissues from multiple human, chimpanzee, and rhesus macaque individuals. These data will allow me to explore conserved inter- tissue regulatory differences, as well as to identify genes and pathways whose regulation evolved under natural selection in primates. In addition, my data will allow me to determine the mechanisms that explain, at least in part, regulatory differences between the species.