UC San Diego

Anthropogeny asks the deepest questions of human curiosity: “Where did we come from? How did we get here?” This dissertation of biomedical sciences takes advantage of molecular and cellular methods to investigate these questions. The human genome is highly similar to the genome of our closest living evolutionary relative, the chimpanzee. Parsing the molecular mechanisms responsible for distinctly-human phenotypes is a daunting challenge. Over recent decades, it has become apparent that the biology of sialic acids, monosaccharides that coat the surface of all cells, is rapidly evolving in the human species. SIGLEC12 and ST8SIA2 are two specific genes involved in sialic acid biology which each contain such human-specific amino acid changes. SIGLEC12 is a cell-surface sialic acid receptor which, in addition to a fixed amino acid change in the human lineage, is experience selection throughout human populations. We discover implications of these evolutionary changes in human cancer risk and progression. ST8SIA2 is a sialyltransferase that is involved in neuroplasticity, neurodevelopment, and in psychiatric and neurodegenerative disease. We identify a single amino acid change in ST8SIA2 that has functional consequences and may contribute to many distinctly human properties of the brain.