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Ran Shi

Blurred image of the arch used as background for stylistic purposes.
Graduate Student
Research Interests:

Mitochondria, like nuclei, cannot be generated de novo and must be inherited. While offspring inherit nuclei from both parents, in most eukaryotes, progeny inherit mitochondria DNA (mtDNA) from the maternal side. The term uniparental inheritance (UPI) is used to describe this phenomenon. In anisogamous species, the biased contribution of mitochondria from two gametes to the zygote and subsequent passive dilution of mtDNA largely explain UPI. For example, in mammals, an oocyte contains 1000 times more copies of mtDNA than a sperm. Additional mechanisms further ensure strict UPI and prevent mtDNA heteroplasmy. Mitochondria UPI (mtUPI) is prevalent in fungi despite the fact that both gametes are of a similar cell size. As isogamy is likely the ancestral state and mtUPI might have existed in the last common eukaryotic ancestor before the divergence of animals, plants, and fungi, studying mtUPI in isogamic species will provide useful insight into the evolution of mtUPI in eukaryotic lineages. Unfortunately, meiotic progeny of the two model yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, can inherit mtDNA from either parent, rendering them unsuitable for studying mtUPI. Here we propose to study mtUPI in Cryptococcus neoformans. This fungus has two mating types, α and a (no mating type switch), equivalent to males and females in mammals. C. neoformans mtUPI was discovered in 2000, and the vast majority of progeny only inherit mtDNA from the a parent. During bisexual mating, an α cell conjugates with an a cell and forms a dumbbell-shaped zygote without nuclear fusion. The two parental nuclei in the zygote duplicate and migrate in congress into the hypha that extends from the zygote. The aerial hyphal tip develops into a basidium head where the two nuclei fuse and meiosis occurs. Studies have shown that UPI is established early in the process of bisexual mating, likely soon after zygote formation. However, how mt-UPI is accomplished in Cryptococcus remains largely unknown. Several hypotheses could explain the mechanism underlying this phenomenon: (1) α mitochondria are excluded from entering the zygote or the resulting dikaryotic hyphae due to an uneven mix of organelles. (2) Alternatively, α mitochondria or its mtDNA is selectively degraded, or (3) a combination of both contributes to strict UPI. My goal is to test these hypotheses and figure out the cellular and molecular mechanism underlying mitochondria uniparental inheritance during sexual reproduction in C. neoformans

Labs (via personnel):
Selected Publications:

Shi, Ran, and Xiaorong Lin. "Illuminating the Cryptococcus neoformans species complex: unveiling intracellular structures with fluorescent-protein-based markers." Genetics (2024): iyae059.


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