Plot: mitochondrial DNA can come from both parents

The vast majority of our DNA – the chromosomes located in the nucleus of each cell – corresponds exactly to what you expect: a mixture of genetic material from both 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 track 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 suffering from extreme fatigue during exercise, while they appeared healthy in many ways, they began to look at its mitochondria, the power plants electrical generating energy in each cell. What they found crushed them: the man had a mitochondrial DNA (mtDNA) identical to that of his father and mother

Since 2002, no other case of inherited mDNA inherited from the father has been reported, despite several research groups. However, an article this week in the PNAS reports mNA 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 daddy's DNA tips in

It is not clear why the mtDNA prefers to be exclusively. maternal, but a higher rate of mutation in the 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, especially mice and sheep, reports in humans have been very limited. In addition to the Danish case, a review of other reports showed that they could all be "attributed solely to contamination and mixing of samples".

Taosheng Huang and his colleagues were anxious to avoid this kind of problem. found strange patterns in the mitochondrial DNA of a patient, they sent new samples to resequencer. The results remained the same: the four-year-old boy had paternal and maternal mtDNA, as did his two sisters.

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, 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 whole families. they were able to establish the pattern of transmission between generations. 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 pbading 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 mtDNA, he pbaded on some of his own mtDNA to his children.

All 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 totally unknown. Understanding the mechanism that allows paternal transmission in these families would help a lot in understanding how mitochondrial transmission works in general – and could also be medically useful. "Two-parent babies", which have 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 a lot to explore: it is possible that evolution is also moving away from paternal mDNA for a very good reason.

Human lineages traced with the aid of mDNA are also likely to have consequences on 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 discovery can spark new and exciting work that will contribute to the pile of research that attempts to refine these estimates.

As fascinating as it may be, 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. The cases of paternal transmission of mtDNA are rare, they add, and seem to leave no fingerprint on the global human genetic record: "The central dogma of maternal transmission of mtDNA remains valid".

PNAS 2018 DOI: 10.1073 / pnas.1810946115 (About the DOIs).