Genetic analysis of systematic mitochondrial heteroplasmy in rabbits

One unusual property of rabbit mitochondrial DNA (mtDNA) is the existence of repeated 153-bp motifs in the vicinity of the replication origin of its H strand. Furthermore, every individual is heteroplasmic: it carries mtDNA molecules with a variable number of repeats. A systematic study of 8 females and their progeny has been devised to analyze mtDNA transmission through generations. The results suggest that three mechanisms are acting simultaneously. (1) Genetic drift in the germ line is revealed by the evolution of heteroplasmy when two major molecular forms are present in a female. (2) A high mutation rate (around 10(-2) per animal generation) generating molecular diversity, by deletion and addition of repeated units, is required to explain the observation of heteroplasmy in every individual. Moreover, the rates of mutation from the most frequent type to the other types are unequal. The deletion of one unit is more frequent than a deletion of two units, which is in turn more frequent than a deletion of three. (3) Selection for shorter molecules in somatic cells is probable. The frequency distribution of mtDNA types depends on the organ analyzed (kidney-spleen and liver vs. gonads).