Contrary to conventional belief that mitochondrial DNA (mtDNA) is generally passed down from mother to offspring, particularly in humans, a new study claims to have identified three “unrelated multigeneration families” in which 17 individuals were found to have inherited a good part of their mtDNA, ranging from 24% to 76%, from their father.
Unlike the rest of our DNA, which reside within the cell nucleus, mtDNA exists separately inside the mitochondria within each cell.
The study, which was led by Dr. Taosheng Huang from the Division of Human Genetics at the Cincinnati Children’s Hospital Medical Center in Ohio, was published Monday (Nov 26) in the Proceedings of the National Academy of Sciences (PNAS).
So entrenched is the belief that mitochondria are inherited from the mother’s side that it is often referred to as the Eve Gene – the logic behind the misnomer being that it can, potentially, be traced back to some primordial matriarch of all humans.
The findings do not only put a big question mark on genetic testing to determine maternal ancestry, but it could also change the way mitochondrial diseases are treated today.
Dr. Huang and his team found their first case of biparental inheritance of mtDNA in a four-year-old boy suffering from fatigue, muscle pain, and other symptoms that hinted at a possible mitochondrial disorder.
Not satisfied with the results of the first sequencing of the boy’s mitochondria, which he thought was “impossible,” Dr. Huang ran subsequent tests at different research labs just to be sure no mistakes were made the first time.
However, each time the results told the same story; Dr. Huang’s four-year-old patient was carrying biparental mitochondrial DNA.
This meant the boy had two sets of mtDNA – one from his mother, which was normal, and the other from his father, which was an aberration – at least as far as the established belief in this regard is concerned.
In pursuance of further confirmation, Dr. Huang and his team tested the boy’s sisters and found the same evidence of biparental mtDNA transmission, which led them to test their mother and, again, the result was no different.
Still not 100 percent convinced, or perhaps in pursuance of more conclusive evidence, the team ran tests on the mother’s parents too, and guess what, 60 percent of her mtDNA came from her mother, while 40 percent had been passed down from her father.
Determined to pursue this further, the researchers ended up identifying 17 individuals from three unrelated families who were carrying biparental mtDNA.
Ten of these mixed mtDNA carriers belonged to the boy’s family alone, while the remaining seven were from the other two unrelated families.
“This upends entire fields based on genetics: under exceptional circumstances, mitochondrial DNA can be passed from father to offspring,” tweeted Trevor Branch – an associate professor at the University of Washington who was not involved in the study.
“This is a really groundbreaking discovery,” Xinnan Wang, a biologist at the Stanford University in California – also not part of the study – was quoted by NOVA Next as saying.
“It could open up an entirely new field… and change how we look for the cause of [certain] diseases,” he told NOVA.
While the original belief that mtDNA is generally a maternal inheritance still stands, the findings do indicate that there are exceptions.
Potentially, the discovery can play a significant role in developing more effective ways for treating mitochondrial diseases, say the researchers.
“Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring,” the researchers wrote in their paper.
“Elucidating the molecular mechanism for this unusual mode of inheritance will provide new insights into how mtDNA is passed on from parent to offspring and may even lead to the development of new avenues for the therapeutic treatment for pathogenic mtDNA transmission,” the authors wrote.
While it’s a fact that each one of us carries a mix of both our parents’ genes, it only holds true in the nucleus.
However, DNA is not just restricted to a cell’s nucleus but also found in the cell’s mitochondria, the so-called “power centers” of the cell, and are referred to as mitochondrial DNA, or mtDNA.
In nearly all known animals, the mtDNA is an exclusive maternal inheritance; hence the “Eve Gene” moniker and the established practice of sequencing mtDNA to determine maternal ancestry.
In our embryonic form, we receive mitochondrial DNA from both Mom and Dad, but Dad’s mtDNA gets discarded long before birth; the reason why this happens still remains a genetic mystery that needs to be researched further.
It is not uncommon for mutant mitochondrial genes to co-exist with healthy ones inside cells, often causing serious diseases; however, the intensity of the affliction is determined by the proportion of mitochondria carrying the mutant gene.
For example, a woman carrying low levels of defective mitochondria can easily pass on higher concentrations to her offspring, with far more serious consequences than what she may have herself experienced.
Apart from the three families researched for the paper, Dr. Huang and his team have traced several other families with biparental mtDNA that are potential subjects for more research.
According to the team, an estimated 1 in every 5,000 individuals has mtDNA from both parents, which is indicative of the fact that biparental transmission of mtDNA may not be as few and far between as was previously thought.
“Clearly, these results will need to be brought in agreement with the fact that maternal inheritance remains absolutely dominant on an evolutionary timescale and that occasional paternal transmission events seem to have left no detectable mark on the human genetic record,” wrote the team.
“Still, this remains an unprecedented opportunity in the field.”