The vast majority of our DNA – the chromosomes in the nucleus of each cell – corresponds exactly to what you expected: a mixture of genetic material from mother and father. But mitochondria are an exception. They contain a relatively small amount of DNA and, in almost all mammals and even unicellular organisms, this DNA comes strictly from the mother. We even used this fact to trace the spread of humanity around the world.
But in 2002, researchers in Copenhagen announced a breathtaking discovery. In order to understand why one of their patients was extremely tired during exercise, while they seemed healthy in many ways, they began to look at its mitochondria, power plants producing energy in each cell. What they found was that the man had mitochondrial DNA (mtDNA) that matched that of his father and his mother's.
Since 2002, no other case of paternally inherited mtDNA has been reported in humans, despite research by several research groups. But an article in this week's newspaper PNAS reports mtDNA inherited from both parents of 17 different people belonging to three families. This type of inheritance is still extremely rare and seems potentially linked to mitochondrial disease, but its robust confirmation in humans is great news for biology and medicine.
The reason why mDNA prefers to be exclusively maternal is unclear, but a higher rate of mutation in paternal mDNA may be for something. With the huge array of mechanisms put in place by different species to prevent intertwined paternal contributions, it seems that evolution holds the contribution of men independently. And while some species have been shown to have a "leakage" of paternal DNA, including mice and sheep, reports in humans have been very limited. In addition to the case in Denmark, a review of other reports argued that they could all be "attributed solely to contamination and mixing of samples".
Taosheng Huang and his colleagues were eager to avoid this kind of problem. Thus, when they discovered strange patterns in a patient's mitochondrial DNA, they sent new samples for resequencing. The results remained the same: the four-year-old boy had paternal and maternal mtDNA, as did his two sisters.
The detective work was just beginning. Huang and his colleagues sequenced the DNA of 11 family members, finding a pattern of paternal contributions. When they examined two other families, both with a family member with a suspicion of mitochondrial disease, they found similar results. In total, they found 17 people in all three families with mixed mtDNA. In all cases, there was a backup check: the whole procedure was "repeated independently in at least two different labs by different lab technicians with newly obtained blood samples," write the researchers.
Because researchers have explored the genomes of entire families, they have been able to determine the mode of transmission from one generation to the next. Some people in families were not affected; they just had a typical maternal mtDNA. It seemed that if a mother had mixed mtDNA, she was passing it directly to the kids – these would inherit the same mix that she had, essentially getting male DNA higher up in the ### 39, family tree. But if a father had mixed mDNA, he passed some of his own DNA to his children.
All of this indicated that the men in the family were the likely source of the emergency exit from the normal paternal stalemate. The schema suggests that there might be a gene in families that would allow paternal DNA to attack the egg with its sperm – and that this gene is probably located in the genome normal nucleic rather than in the mtDNA itself. This genetic trait could then be transmitted, giving each male who inherits it the ability to transmit his mtDNA to his offspring.
Consequences for medicine and evolution
How precisely this happens is still completely unknown. Understanding the mechanism that allows for paternal transmission in these families would help a lot in understanding how mitochondrial transmission works in general – and it could also be medically useful. "Two-parent babies", which have a mtDNA from a donor to prevent the transmission of mitochondrial disease, are a recent, controversial and expensive development. Therefore, if there is a way to survive paternal mDNA, it may offer another treatment option. However, there is much to explore: it is possible that evolution is so far away from paternal mDNA for a very good reason.
With human lineages traced through mDNA, there are also consequences for our understanding of human evolution. That said, genetic estimates of population divergence are based on a wide range of data, much of which is still subject to ongoing debate and discovery. This finding could lead to new and exciting work that will contribute much of the research to refine these estimates.
As fascinating as this discovery is, the paucity of paternal transmission deserves to be underlined. "The maternal inheritance remains absolutely dominant on a scalable time scale," write Huang and his colleagues. Cases of paternal transmission of mtDNA are rare, they add, and seem to have left no fingerprints on the overall human genetic record: "The central dogma of maternal transmission of mtDNA remains valid".
PNAS, 2018. DOI: 10.1073 / pnas.1810946115 (About the DOIs).