Mitochondrial genotype segregation and the bottleneck

Mitochondria can produce a wide range of effects on many physiological systems, and these effects and their severity can vary with the ratio of mutant and wild-type mitochondrial genotype, i.e. heteroplasmy. It is therefore critical to understand the biological mechanisms controlling the segregation of mitochondrial genes, not only in somatic tissue, but also in the germ cell lineage, since the latter is the means of transmission of pathological mutations across generations. The bottleneck hypothesis was proposed to explain the homogeneity of mitochondrial genomes within organisms. This review addresses information available both from in-vitro cellular models and in-vivo animal models that have been designed to investigate mitochondrial DNA segregation in somatic and in germ cells at different stages of development. It appears that segregation occurs in multiple steps during development, and not in a single location or a single time during germ cell transmission. Nonetheless, persistent heteroplasmy of some lineages, replicative advantage of seemingly neutral genotypes and the effect of nuclear background on mitochondrial DNA segregation patterns are only a few of the observations that remain unexplained. Only after further characterization of these mechanisms will we be able to provide proper reproductive counselling to women carrying heteroplasmic mitochondrial DNA.