The DNA of eukaryotic organisms (such as animals, plants and fungi) is stored in two cellular compartments: in the nucleus and in organelles called mitochondria, which transform nutrients into energy to allow the cell to function. The nucleus harbours most of our genes, tightly packaged into 46 chromosomes, of which half are inherited from our mother’s egg and half from our father’s sperm. By contrast, mitochondrial DNA (mtDNA) was thought to derive exclusively from maternal egg cells, with no paternal contribution1. Writing in Proceedings of the National Academy of Sciences, Luo et al.2 challenge the dogma of strict maternal mtDNA inheritance in humans, and provide compelling evidence that, in rare cases, the father might pass on his mtDNA to the offspring, after all.
Human eggs contain more than 100,000 copies of mtDNA, whereas sperm contain approximately 100 copies3. Early hypotheses suggested that paternal mtDNA molecules became diluted in number relative to maternal mtDNA ones in the fertilized egg, but these ideas were replaced when evidence from various organisms, such as the uni-cellular alga Chlamydomonas reinhardtii4 and medaka fish5, showed that paternal mtDNA is rapidly eliminated after fertilization. For decades, researchers have speculated on why healthy organisms obtain their cellular powerhouses from just one parent and on the possible evolutionary advantages conferred by mitochondrial genes inherited in this fashion.
A healthy individual’s mtDNA molecules are mostly identical. But in people with diseases caused by mtDNA mutations, normal and mutant mtDNA molecules typically coexist in a single cell — a situation termed heteroplasmy6. Disease severity is often associated with the amount of mutant mtDNA in cells, which is in turn determined by events that occurred when the person’s mother was still an embryo7. The developing eggs in the female embryo go through an ‘mtDNA bottle-neck’, in which the number of mtDNA copies is first reduced and then amplified to more than 100,000 copies8,9. Accordingly, variable amounts of mutant and normal mtDNA are present in the mature eggs of an individual woman, and, therefore, in the cells of her offspring. This phenomenon influences the severity of diseases caused by mtDNA mutations, and can lead to very different manifestations between individuals from the same family7.