Aditi Trivedi

ELUCIDATING THE MECHANISM OF PURIFYING SELECTION USING C. ELEGANS

Inheriting healthy mitochondrial DNA from the maternal line is necessary for proper energy metabolism, growth and thus, organismal viability. Accumulating mitochondrial DNA mutations over many generations would lead to improper energy production, mitochondrial disease and, if kept unchecked, possible extinction of a line. Such malfunctions are prevented by the mechanism of purifying selection, an essential step towards transmission of healthy mtDNA. However, this mechanism is not well understood. Here we investigate the rate of purifying selection and genes involved, focusing on oogenesis in the germline using C. elegans. Because apoptosis in the germline kills >90% of potential oocytes, and can regulate the types of cells and DNA molecules inherited, we are specifically studying the involvement of germline apoptosis in mtDNA inheritance. We will compare the rates of purifying selection in both mtDNA and pro-apoptotic/mtDNA double mutants using qPCR. Preliminary experiments show the mitochondrial translation-inhibiting drug, Chloramphenicol, in combination with another antibiotic, acts as a possible selection condition for differential growth of WT and mtDNA-mutant (JR3630) strains, allowing for preferential viability. In addition, using molecular genetics techniques, we created a double mutant strain (ced-3(n717); uaDf5//++), which will be used to test germline apoptosis involvement in purifying selection. By understanding purifying selection through germline apoptosis, we hope to uncover exciting information that shows promise toward treating and curing inherited mitochondrial myopathies.