[
International Worm Meeting,
2015]
The mitochondrial genome (mtDNA) is present in many copies within each cell and follows a maternal pattern of inheritance. mtDNA experiences a high mutation rate which leads to heteroplasmy, in which a mixed population of both wildtype and altered mtDNA exist within the same cell. While each mtDNA can act as a "selfish DNA" element, purifying selection is used to eliminate from the germline mtDNAs that are defective and debilitate mitochondrial function. We are investigating the mechanisms used in purifying selection in the germline. One level at which purifying selection might act is during the early embryonic divisions that establish the germline (P lineage). We have obtained preliminary evidence that the most active mitochondria (those with the highest membrane potential) are enriched in the germline lineage during the early embryonic cell divisions. Following this early phase, we found that germline mitochondria are then fully quiescent (no detectable membrane potential) until after the initiation of larval development. We have taken advantage of a 3 kb mtDNA deletion, uaDf5 [Tsang et al 2002], to investigate further the mechanisms that remove defective mtDNAs. This deletion exhibits stable heteroplasmy, raising the suggestion that it is maintained as a result of complementing mutations on the non-deleted mtDNAs in the strain [Tsang et al 2002]. However, we found that the uaDf5-bearing strain appears to contain fully intact, wild-type mtDNA, suggesting that the deletion may be maintained as a result of replicative advantage. Further, we found that the uaDf5 strain gives rise to arresting embryos with many cell corpses, reminiscent of cells that have undergone programmed cell death. Lines that generate arresting embryos at highest frequency also show extended lifespan in the survivors, consistent with a trade-off between mitochondrial function required for survival and lifespan extension. Finally, we have obtained preliminary results suggesting that physiological state of worms influences the rate of removal of mtDNAs encoding defective proteins. We are investigating the trans-generational dynamics of this apparent purifying selection.