Molecular Genetics

Mendelian principles have been the cornerstone for identifying nuclear genes in biological and diseases processes and ordering these genes into functional cascades. However, the limitation of Mendelian genetics to explain many complex traits has redirected attention beyond the nucleus. In addition to the nuclear genome, each eukaryotic cell contains hundreds to thousands of copies of mitochondrial genome, the small circular DNAs inside mitochondria. Mutations on mitochondrial genome often impair cellular energy homeostasis and have been linked to many diseases including various age-related disorders. Despite the immense impact of mtDNA mutations on health and disease, our understanding of mitochondrial genetics remains rudimentary. Genetic analyses on mitochondrial genome are complicated by the peculiarities of the mitochondrial genetic system that features maternal inheritance, polyploidy, and amitotic segregation.

We are working with fruit flies and other model organisms to understand the basic principles guiding the transmission of mitochondrial genome. We are trying to understand why evolution favors the transmission of mitochondrial genome from the maternal linage exclusively, how mothers limit the transmission of harmful mtDNA variants to their offsring, how organisms prevent the accumulation of mtDNA mutations in somatic tissues and with aging. We are also exploring the coordination and potential genetic conflicts between nuclear and mitochondrial genome, and their impact on health and diseases. Additionally, we are actively developing new tools to advance the genetic study of mtDNA.