Mitochondrial DNA (mtDNA) sequences are currently studied mainly by three disciplines: molecular evolution (including anthropology), functional genomics and analyses of genetic disorders. Strangely, these disciplines can use the relatively short sequence of mtDNA in opposing manners, by attributing to it either lack of function, as is the case in (some) molecular evolution studies, or conversely, functional relevance in the aetiology of genetic disorders.

In the field of molecular evolution, mtDNA has been considered an excellent marker for tracing ancient migrations because of its uniparental (maternal) inheritance and lack of recombination. These mtDNA characteristics prompted Rebecca Cann, Mark Stoneking and Allan Wilson to analyse the mtDNA in 147 human samples collected from people representing all major global populations. The most important discovery of their work was that the highest degree of mtDNA variation was found among Africans, attesting to their antiquity. The other finding was that although mtDNA from across the globe contained African types, Africans had many unique mtDNA types.

mtDNA has been considered an excellent marker for tracing ancient migrations because of its uniparental (maternal) inheritance and lack of recombination

These two findings, in addition to other data, prompted Cann et al. (1987) to propose that the origin of all current human populations (at least the maternal lineage) is likely African. Many criticized this study, especially because their African samples originated mainly from Afro-Americans rather than from indigenous African populations. Nevertheless, subsequent studies, which used more advanced techniques and better-sampled populations, supported this pioneering and game-changing work of Cann et al.

In the year following the publication of the above article, Douglas C. Wallace and colleagues published the first report of mtDNA mutations causing a disease — Leber’s hereditary optic neuropathy. As disease-causing mutations are amenable to natural selection, how could one consider the mtDNA to be merely a neutral marker? It was this contradiction that drew me into studying mitochondrial biology and to discovering that even common population variants of mtDNA are both subjected to natural selection and alter the tendency to develop genetic disorders.