Evolutionary Annotation of Regulatory Sequences
Why are humans different from other mammalian species? This question is as compelling as any in science, but has been extremely difficult to answer. It is known that the distinctive features of human biology are largely the result of evolutionary changes to our genome. But most of the exact connections between genomic change and phenotypic innovation remain unclear. Professor Ma’s long-term goal is to utilize comparative genomics to better understand the relationship between genomic differences and phenotypic diversity across mammalian species, which will in turn help understand the human genome and identify key genetic variants related to diseases.
At the level of gene transcription, gene expression is controlled via transcriptional regulatory proteins that selectively bind to regulatory elements in non-coding regions of the genome. It is acknowledged that genetic changes in these gene regulatory elements are a major cause of phenotypic differences between human and other mammalian species. Despite the recent advancement in both experimental and computational methods to identify potential regulatory elements, we know very little about when these elements came to the human genome during evolution (e.g. did they emerge before human-chimpanzee divergence or before human-macaque divergence?), how they have evolved, and what would be their distinct functional impacts on human biology. Currently, there is no existing method that can comprehensively annotate the detailed history of regulatory elements. To tackle this challenge, Professor Ma and his research team will develop new algorithms to trace the history of regulatory elements in mammalian evolution. He will then annotate and validate the evolution of regulatory elements in the human genome by combining functional genomics with cross-species sequence comparisons. The project is highly interdisciplinary, involving research in genomics, computer science, evolutionary biology, and molecular biology. The research will have the potential to help discover regulatory elements that contribute to species-specific traits in mammalian evolution and human biology.