How One Woman Brought the ‘Mother’s Curse’ to Canada

The first King’s Daughters—or filles du roi—arrived in New France in 1663, and 800 more would follow over the next decade. Given their numbers, they were not literally the king’s daughters of course.

They were poor and usually of common birth, but their passage and dowry were indeed paid by King Louis XIV for the purpose of empire building: These women were to marry male colonists and have many children, thus strengthening France’s hold on North America.

And so they did. The filles du roi became the founding mothers of French Canadians, for whom these women are a source of historical pride. A grand old restaurant in Montreal was named after the filles du roi. So is a roller-derby team. French Canadians can usually trace their ancestry back to one or more of these women. “French Canadian genealogy is so well documented, it’s just a piece of cake to trace any line you have,” says Susan Colby, a retired archaeologist who comes from a French Canadian family and has done some of that tracing herself.

So well-documented is French Canadian genealogy that professional geneticists and demographers use the data for research, too. Whenever a small group of people leave a large population (France) to found a new one (New France), they bring with them a particular set of mutations. Some of these mutations will by chance be more common in the new population and others less so. As a result, some rare genetic disorders disproportionately impact French Canadians.

One of these is Leber’s hereditary optic neuropathy, which causes vision loss, usually in young men. Recently, geneticists using French Canadian genealogy have reexamined the effects of Leber’s and found a striking pattern of inheritance: It seems to show a long-theorized but never-seen-in-humans pattern called the “mother’s curse.”

Before all this, the most convincing evidence of the mother’s curse came from fruit flies.

The idea for the mother’s curse goes like this. Most human genes are on chromosomes, but a tiny number are in mitochondria, little power factories in human cells that for reasons of evolutionary history have their own loops of DNA. Sperm do not pass on any mitochondria, but eggs do. Therefore, all sons and daughters inherit their mitochondrial DNA from their mother. If a harmful mutation in mitochondrial DNA ends up in a woman, she will be less evolutionarily “fit” and thus less able to pass it along. But if the mutation ends up in a man, nothing happens. He never passes along mitochondrial DNA anyway.

The trouble comes when the mutation harms men but not women; then there is no way for natural selection to weed it out. The mother’s curse is passed on to her children. (There is no equivalent father’s curse, because the Y chromosome is passed only to men and cannot affect women.) For example, Damian Dowling, a geneticist at Monash University, has found a gene in fruit flies that makes males completely sterile but somehow seems to be selected for in females.

Read: Your body acquires trillions of new mutations every day

For many years, says Dowling, Leber’s hereditary optic neuropathy has been on the radar of evolutionary biologists interested in the mother’s curse. Doctors knew that the mutation causing the disorder sits on mitochondrial DNA, and they have noticed that it seems to affect men eight times more than women.

In 2005, researchers at the Université de Montréal actually traced the ancestry of 11 modern-day patients with Leber’s back to a single fille du roi who came to New France at the age of 18. Her particular mutation is responsible for 89 percent of Leber’s cases in the Quebec population. By following her daughters, granddaughters, great-granddaughters and so on all the way to the present, it is possible to identify people who had lived with this particular Leber’s mutation over a 290-year period in the area. “It was the ideal setup to test the mother’s-curse hypothesis,” says Emmanuel Milot, a geneticist at Université du Québec à Trois-Rivières.

Milot and his colleagues ended up sorting people in the French Canadian genealogy databases by whether they had the Leber’s mutation and counting up their number of descendants. In straight evolutionary terms, the more descendants you have, the more “fit” you are. The men carrying the Leber’s mutation, it turned out, were indeed slightly less fit than men who did not, as well as women who did. Because of this pattern, the mutation harmful in males does not get weeded out at all over 290 years. It appears to be an example of the mother’s curse at work.

If the mother’s curse is real in humans, that opens up a whole host of other questions in biology. Women usually live longer than men—could some of that difference be explained by mother’s-curse mutations that have accumulated in mitochondrial DNA? (Milot thinks so.) And how is it, exactly, that the same mutation can be harmful in men but benign in women?

One hint comes from a recent study published in the European Journal of Human Genetics, which linked mitochondrial dysfunction to lower fertility in men. Sperm do not contribute any mitochondria to an embryo, but they themselves are packed with mitochondria that power their swim toward the egg. “Anything goes wrong with mitochondria, those sperm are not going to fertilize an egg,” says Dowling. That could be why mitochondrial mutations may impact fertility in men more than women.

When scientists first coined the “mother’s curse” years ago, it was a just an evocative name for a hypothesis. After publishing his study, Milot heard from a woman who wrote to him lamenting she had the mother’s curse. She had passed a mutation, though not for Leber’s, on to her son. “When I received her message,” says Milot, “I thought, ‘My God, maybe we should have chosen another name.’”

The “mother’s curse” has been used in the scientific literature for years—long before anyone applied it to a specific human mutation, before anyone traced it to a single fille du roi. It is only now that theoretical evolutionary biology has to confront human reality.