Research Project
9439382
Mitochondria are components of cells that generate molecules of energy used to power critical processes that sustain life. At fertilization, most sexually reproducing organisms, like humans, obtain half of their genes from each parent. Mitochondria have their own DNA genomes, which encode the proteins responsible for the generation of that cellular energy. However, the existing paradigm in biology is that offspring in most species, including humans, obtain their mitochondria not from both parents but only from the mother. This establishes the situation where mutations in mitochondrial DNA that disrupt energy production are passed from affected mothers to all of their children at fertilization. Sperm contain mitochondria as well, but they are not normally passed on to offspring. Consensus is weak on whether eggs have components that recognize and destroy sperm mitochondria and/or whether sperm initiate their own mitochondrial self-destruction prior to fertilization. Although much is known about how mitochondria produce energy, much less is known about this process of paternal mitochondrial elimination, including the identities of all of the molecular components and whether and how oocytes distinguish sperm mitochondria from their own. The long term objective of this project is to identify the genetic and molecular basis of paternal mitochondrial elimination. Interestingly, previous studies have suggested that paternal mitochondrial elimination does not occur effectively in hybrids of some species, suggesting genetic mapping of paternal mitochondrial transmission in those species as a method for identifying genes involved in paternal mitochondrial elimination. As part of this project, existing hybrids of an animal model system will be generated and phenotyped for the presence of paternal mitochondria. Existing genotype data from those hybrids will be analyzed along with the phenotype data to map loci involved in paternal mitochondrial transmission. In a complementary approach, new hybrids will be generated to assess how widespread is paternal mitochondrial transmission in this system. Separately, existing sex determination mutants will be used to address the question whether sperm inherently generate their own signal that marks sperm-borne mitochondria, or whether production of that signal is directed by male somatic tissue. Outcomes of this research project are directly relevant to informing policy decisions about the use of three-parent fertilization and other clinical interventions for circumventing maternal mitochondrial inheritance and also to diagnosing heritable mitochondrial genetic disorders in humans.
