Mammalian mitochondrial DNA (mtDNA) shows a high mutation rate. It is inherited in a non-Mendelian manner only
from the mother. So, these maternally derived mtDNA molecules are segregated through cell division events in the developing embryo to generate
primordial germ cells with approximately 950–1,550 mtDNA copies. Replication of mtDNA is reinitiated as the primordial germ cells migrate and differentiate to generate oocytes transmitting mtDNA to the next generation. The mtDNA bottleneck appears to result from the replication of only a small subset of the mtDNA molecules as the primordial germ cells differentiate to generate oocytes. In humans, a considerable amount of mtDNA sequence is available from individuals as a result of studies into human evolution and human mtDNA diseases. Consensus is forming that
selection is an important part of mtDNA sequence variation in human mtDNA, but the strength and nature of this selection are unresolved.Though population-level studies detect signatures of purifying selection in mtDNA sequence variation, recent accumulated variation within human populations implies neutrality or weak selection on these variants. Findings from studies of mtDNA mutation inheritance in families with mtDNA-associated disease are compatible with the occurrence of only very weak or no selection on these mtDNA mutations. In this study, this high mtDNA mutation rate was utlised to study the transmission of random mtDNA mutations in the mouse germ line. Female lineages were derived from mtDNA mutator mice by continuous backcrossing, allowing us to isolate, segregate, and characterize germ line mtDNA mutations.