Research led by Professor Patrick Chinnery (Department of Clinical Neurosciences & MRC Mitochondrial Biology Unit) has uncovered how mitochondrial DNA (mtDNA) is inherited down the maternal line in humans. The results of the research, published in Nature Cell Biology, shows that Mammalian cells contain many copies of mtDNA. When a mutation is present it can affect different proportions of the mtDNA molecules (mtDNA heteroplasmy). Isolating germ cells from early human embryos, the researchers discovered heteroplasmic mtDNA variants in all of the healthy embryos studied by high depth sequencing.
Measuring the amount of mitochondrial DNA in single germ cells, they observed a drastic reduction in the amount of mitochondrial DNA during germ cell development which creates a “bottleneck effect”, explaining the dramatic shifts in percentage heteroplasmy level they observed during germ cell development. ‘This is explains how mtDNA disease can present without a prior family history, and why different siblings can have very different clinical phenotypes’ said Prof Chinnery. Intriguingly, they also saw evidence of selection against deleterious mtDNA variants, explaining why there has not been a relentless accumulation of mtDNA mutations in human species which, if left unchecked, would lead to ‘mutational meltdown’ and extinction of the species.