ACSH Tries to Explain: The Mother’s Curse

By Chuck Dinerstein, MD, MBA — Jul 05, 2023
For the most part, our genetic heritage is a “crap shoot” mixture of mom and dad. But the DNA of the engines powering our bodies, mitochondria, are inherited only from mom, which makes for some biological differences, including the Mother’s Curse.
Image by PublicDomainPictures from Pixabay

Most of our genes lie within the nucleus of our cells. Mutations in the DNA that constitutes our genome can be beneficial, neutral, or harmful. Through cellular repair and natural selection, harmful mutations tend to get weeded out. But 37 of our genes lie within our mitochondria cellular powerhouses. Our mitochondrial genome, mtDNA, comes exclusively from our mothers; they are maternally inherited. [1] For our sisters, the same rules apply; mutations that would be harmful to them are weeded out.

But for the males, no such luck. Mutations harmful to us that might indeed kill or maim us continue to be passed along through the unharmed females. This difference allows for deleterious mutations to bypass the normal evolutionary pressures creating a high frequency of male-specific mutations and decreasing our evolutionary “fitness.”  This was a hypothesis in the 1960s but became a scientific fact in the 2000s. To understand that, we must visit our friends to the North, Canada.

Optical Neuropathy and the Sun King

There is a disease called Leber hereditary optical neuropathy (LHON) which can cause many neurologic problems, including blindness. It is due to a genetic mutation T14484C and affects males 8-fold more than females. Ironically, the increased prevalence of T14484C in French Canadians is due to an attempt to correct another disparity between men and women. That disparity, a lack of women, was present in the early colonies in what was to become Canada and was, at the time New France.

To incentivize migration, Louis XIV, the Sun King, began shipping unmarried French women,  filles du roi or “king’s daughters,” to New France, along with generous dowries. [2] Over ten years, 800 women married and had children in New France.

Using a genealogical database and marriage records, researchers traced the T14484C mutation back to one of the King’s Daughters, who married in Quebec City in 1669 at age 18. This mutation accounts for 89% of French Canadians with LHON. Of the 2,000 carriers of the mutation they unearthed, not literally, male carriers had a 20% lower survival rate in the first year of life than females, along with a lower chance of marrying and becoming a father. T14484C was a man-killer.

As a result of this maternal inheritance, evolutions’ selective pressure is disparately employed against the male. There are other examples, most interestingly, a finding in fruit flies that variations in mtDNA resulted in increased aging in males but not in females. Could the Mother’s Curse help explain females' ever-present, more remarkable survival over males?

The impact of the Mother’s Curse is not complete. Paternal leakage, where some of the paternal mtDNA survive, exists, albeit at a low frequency, and may counteract the deleterious effects of maternal mtDNA. The Mother’s Curse also helps to explain a recent breakthrough, the three-parent child.

One child, three parents

The technique, mitochondrial replacement therapy (MRT), was approved in the UK in 2015 and is directed at the problematic mitochondria present in the mother. The nucleus of her fertilized egg is removed and placed in an egg of a donor where the nucleus has been removed, leaving only the healthy mitochondria. The baby has its parents' genes and the healthy donor's mitochondria.

There have been five babies born after MRT in the UK, and Australia has become the second country to approve the use of this technique; it remains unapproved in the US. Preliminary reports indicate that the children are healthy, although there was a reversal and return on the original mother’s mitochondria in one instance.


[1] The mitochondria of sperm are destroyed when they enter an egg cell.  

[2] British colonies to the South did not have such problems for two interesting reasons. First, most British colonists were farmers and brought their wives along; the French were primarily hunters, trappers, and Jesuits and led a more solitary life. Second, the British let anyone migrate; the French were not keen on allowing the Protestants to spread their “evil ways” to the colonies and kept them close at hand.


Source: The Mother’s Curse: how a French king’s legacy revealed a loophole in evolution Massive Science


Chuck Dinerstein, MD, MBA

Director of Medicine

Dr. Charles Dinerstein, M.D., MBA, FACS is Director of Medicine at the American Council on Science and Health. He has over 25 years of experience as a vascular surgeon.

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