A rare family has many more sons than daughters for generations

You probably know of a family where the children are almost all boys or all girls. In most cases it’s just a coincidence, but an analysis of a family in Utah dating back to the 18th century revealed a possible biological explanation: a selfish Y chromosome that somehow prevents women from giving birth.

“This is a very important family,” he says James Baldwin-Brown at the University of Utah. “Selfish genes of the kind we’re talking about have been found in many organisms, but they’ve been very difficult to study in humans.”

In most mammals, male cells have one X and one Y chromosome. When the stem cells in the heads divide to form sperm, half should carry Y and half X, meaning there should be a 50:50 chance that any offspring will be male or female. However, some chromosomes have genetic variants that allow them to skew this ratio, resulting in more male or female offspring. For example, some selfish chromosomes disrupt the ability of other sperm to follow a scent trail toward the egg. Other selfish chromosomes kill any sperm that don’t carry them, though it’s not clear how they manage this. “That’s a 100-year-old question that we’re still working on today,” he says Nitin Phadnisalso at the University of Utah.

In some cases even evolutionary battles between the selfish X and Y chromosomeswith each competing to skew the gender ratio in its favor and against the mechanisms used by its competitors. Because selfish chromosomes that skew the sex ratio have been found in many different animals, there is every reason to think they exist in humans, but identifying the selfish chromosomes that are active today is tricky. “Even if you have five, six or seven boys in a row, say, the likelihood of that happening by accident is pretty high,” says Baldwin-Brown.

The only way to get the numbers needed to show that a skewed ratio is extremely unlikely to be a coincidence is to look at multiple generations. Baldwin-Brown, Phadnis and their colleagues realized they could do this using a population-based database in Utah that contains details on millions of individuals, although they tracked only 76,000 for this study.

The team analyzed the data using two separate statistical methods, both of which picked the same family as a significant outlier. Over seven generations, 33 men inherited the same Y chromosome. Of the 89 children these men had, 60 were male and only 29 were female.

Because the data is anonymized, the team was unable to perform any genetic analyses. “It would be great if we could de-anonymize these samples and go to these people and say, ‘Hey, can we sequence your sperm and try to understand what’s going on here?'” says Baldwin-Brown. “But that’s a pretty big hurdle because ethically it requires a lot of paperwork and a lot of money.”

SarahH Zanders of the Stowers Institute for Medical Research in Missouri, says she would like to think the team has found a selfish Y chromosome, but that the numbers are still too small to be sure. When studying the microbes, her team found significant biases in the sex ratio more often than expected, but these findings were mostly noise that disappears when larger sample sizes are analyzed.

There’s also the potential issue of infidelity, Zanders says. “I’m not a people expert, but my heuristics based on watching trashy TV tell me that there could have been several times the wrong paternity was determined.” Baldwin-Brown says his team considered that possibility. “We still have a lot of reliable data that we think is reliable,” he says.

Identifying selfish Y chromosomes is not a purely academic concern, says Phadnis. They can contribute to surprisingly high rates of male infertility. A mechanism that kills half of all sperm will obviously reduce fertility, he says. What’s more, animal studies have also shown that selfish chromosomes can lead to infertility in some individuals.

The researchers now plan to analyze sperm samples to look for skewed ratios of X- and Y-carrying sperm.

In the latest study, they looked specifically for selfish Y chromosomes for several reasons. First, it is easy to trace male lines. Second, there are other potential explanations for the increased number of female children: they may be due to lethal mutations, not just selfish X chromosomes.

Selfishness is not limited to the X and Y chromosomes. More generally, any piece of DNA that can increase the probability of being inherited above 50 percent is known as a gene drive, and many different types have been discovered in animals. CRISPR gene editing technology has been used to create artificial gene units that are being considered to stop the spread of malaria or fight pests.

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