X and Y chromosomes can compete against each other to skew sex ratios in their favour
KATERYNA KON/SCIENCE PHOTO LIBRARY
You probably know of a family where the children are almost all boys, or all girls. In most cases, it is just due to chance, but an analysis of a family in Utah going back to the 1700s has identified a possible biological explanation: a selfish Y chromosome that somehow prevents females from being born.
“This is a very significant family,” says James Baldwin-Brown at the University of Utah. “Selfish genes of the kind that we’re talking about have been found in lots of organisms, but they’ve been very hard to study in humans.”
In most mammals, male cells have one X and one Y chromosome. When stem cells in the testes divide to form sperm, half should carry a Y and half an X, which means there should be a 50:50 chance of any offspring being male or female. But some chromosomes have genetic variants that enable them to skew this ratio, resulting in more male or female offspring. For instance, some selfish chromosomes disrupt the ability of other sperm to follow a scent trail towards an egg. Other selfish chromosomes kill off any sperm that don’t carry them, though how they manage this is unclear. “That’s a 100-year-old question that we’re still working on today,” says Nitin Phadnis, also at the University of Utah.
In some cases, there are even evolutionary battles between selfish X and Y chromosomes, with each competing to skew sex ratios in its favour and counter the mechanisms used by its competitors. Because selfish chromosomes that distort sex ratios have been found in many different animals, there is every reason to think they exist in people, but identifying selfish chromosomes that are active today is tricky. “Even if you have five, six or seven boys in a row, say, the odds of that happening by chance are pretty high,” says Baldwin-Brown.
The only way to get the numbers needed to show that a skewed ratio is extremely unlikely to be down to chance is to look at multiple generations. Baldwin-Brown, Phadnis and their colleagues realised they could do this using the Utah Population Database, which has details on millions of individuals, though for this study they looked at just 76,000.
The team analysed the data using two separate statistical methods, which both picked out 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 just 29 were female.
Because the data are anonymised, the team hasn’t been able to do any genetic analyses. “It’d be great to be able to de-anonymise these samples and go to these people and say, ‘Hey, can we sequence your sperm, try to understand what’s going on here?’” says Baldwin-Brown. “That’s a pretty big hurdle, though, because to do that ethically requires a lot of paperwork and a lot of money.”
SaraH Zanders at the Stowers Institute for Medical Research in Missouri says she would like to think that the team has found a selfish Y chromosome, but that the numbers are still too small to be sure. While studying microbes, her team has found significant biases in sex ratios more often than would be expected, but these findings have mostly been noise that disappears when larger sample sizes are analysed.
There is also a potential issue with infidelity, says Zanders. “I am not an expert on humans, but my heuristics, built on watching trashy TV, tell me that mis-assigned paternity may have happened a few times.” Baldwin-Brown says his team has considered this possibility. “We still have a lot of solid data that we think is reliable,” he says.
Identifying selfish Y chromosomes isn’t purely of academic interest, says Phadnis. They may contribute to the surprisingly high rates of infertility among men. A mechanism that kills half of all sperm will obviously reduce fertility, he says. What’s more, studies in animals have also shown that selfish chromosomes can result in infertility in some individuals.
The researchers now plan to analyse sperm samples to look for skewed ratios of X- and Y-carrying sperm.
They looked specifically for selfish Y chromosomes in the latest study for a couple of reasons. Firstly, they are easy to trace down male lineages. Secondly, there are other potential explanations for an increased ratio of female children: they can be due to lethal mutations, not just selfish X chromosomes.
Selfishness isn’t limited to X and Y chromosomes. More broadly, any piece of DNA that can boost its odds of being inherited beyond 50 per cent is known as a gene drive, and many different kinds have been discovered in animals. CRISPR gene-editing technology has been used to create artificial gene drives whose use is being considered for stopping the spread of malaria or tackling pest species.
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