The vast majority of our DNA-the chromosomes in the cell of every cell is just what you expect: a mix of genetic material from both mother and father. But mitochondria are an exception. They contain a relatively tiny amount of DNA, and in almost all mammals and even unicellular organisms, that DNA comes from strictly from the mother. We've been also used to trace the humanity around the world.
But in 2002, researchers in Copenhagen reported a jaw-dropping finding. In many cases, they started examining his mitochondria-the energy-generating power stations in each cell. What they found floored them: the man had mitochondrial DNA (mtDNA) that matched both his father's and his mother's.
Since 2002, no other cases of paternally inherited mtDNA have been reported in humans, despite many research groups actively looking. But a paper in this week's PNAS reports mtDNA inherited from both parents in 17 different people from three families. This kind of inheritance is still very rare and seems potentially linked to mitochondrial disease, but the robust confirmation of it in humans is a huge news for biology and medicine.
Dad's DNA butts in
It's not clear why mtDNA prefers being exclusively maternal, but a higher rate of mutation in mtDNA may have something to do with it. With the huge array of mechanisms that different species have evolved to prevent interloping paternal contributions, it seems that the evolution is holding men's contribution at arm's length. And while some species have found to have "leaking" paternal DNA, including mice and sheep, reports in humans have been very limited. Aside from the case in Denmark, they could all be "ascribed solely to contamination and sample mix-up."
Taosheng Huang and his colleagues were keen to avoid that kind of problem, so when they found the weird patterns in a DNA, they sent new samples to be resequenced. The results came back the same: the four-year-old boy had both paternal and maternal mtDNA, and so did his two sisters.
The detective work was just beginning. Huang and his colleagues sequenced the mtDNA of 11 people in the family, finding a pattern of paternal contributions. When they looked at two other families, both with a family member with suspected mitochondrial disease, they found similar results. Altogether, they found 17 people across the three families with mixed mtDNA. In all cases, there was a backup check: the whole procedure was "repeated independently in at least two different laboratory technicians with newly obtained blood samples," the researchers write.
Because the researchers explored genomes of whole families, they were able to work out the transmission of transmission across generations. Some people in the families were not affected; They just had typical maternal mtDNA. It seemed that if a mother had mixed mtDNA, she passed that mixture directly to the kids-the kids would inherit the same mixture she had, essentially getting male mtDNA from further up in the family tree. But if a father had mixed mtDNA, he passed some of his own mtDNA on to his kids.
All of these pointed to the men as the source of the escape hatch to the normal paternal dead-end. The pattern suggests that there could be a gene running in the family that allows paternal mtDNA to hitch a ride into the egg with their sperm-and that gene is in the normal, nucleic genome rather than the mtDNA itself. That genetic trait could then get down, giving every male that inherits it the capacity to pass their mtDNA to their offspring.
Consequences for medicine and evolution
How, precisely, this happens is still completely unknown. Understanding the mechanism that allows paternal transmission in these families would be a huge boost to understanding how mitochondrial transmission works in general-and it could be useful medically, too. "Three-parent babies," who have mtDNA from a donor to prevent transmission of mitochondrial disease are recent, controversial, and expensive development-so if there is a way to get paternal mtDNA to survive, it could provide an alternative possibility for therapy. There's a lot to explore there, however: it's possible that evolution veers so strongly away from maternal mtDNA for a very good reason.
With human lineages traced through mtDNA, there are potential consequences for our understanding of human evolution, too. That said, genetic estimates of when populations diverged on a wide range of data, much of which is still subject to debate and ongoing discoveries. This finding may spark new and exciting work, which will contribute to the assessment of those estimates.
As thrilling as this discovery is, the rarity of paternal transmission is worth emphasizing. "Maternal inheritance remains absolutely dominant on an evolutionary timecale," write Huang and his colleagues. Cases of paternal mtDNA transmission are rare, they add, and seem to have left no fingerprint on the overall human genetic record: "The central dogma of maternal inheritance of mtDNA remains valid."
PNAS, 2018. DOI: 10.1073 / pnas.1810946115 (About DOIs).