What's happening to the Y chromosome?

Although it appears that 97% of genes have been lost from the male-only chromosome, the latest research suggests its future is safe. Yi-Di Ng and Elizabeth Finkel report.

The Y chromosome carries genes that are not only crucial for sex determination, but individual survival. – iStock

The Y chromosome is highly prized. But in truth it is only one of many ways that nature ordains the male of the species. Reptiles rely on temperature, birds use two “Z” chromosomes and for fruit flies it all depends on how many X chromosomes they carry.

Until recently it seemed that the human Y chromosome was about to undergo a sea change. Researchers believe it was once the same size as its partner, the X chromosome. But over the past 180 million years, the Y shed its genes at an alarming rate. Today it’s a stumpy little sidekick, carrying less than 3% of the 800 or so genes of its partner. It’s been dubbed the “rotting Y” but how far can it rot? Could men become like the European mole vole, which lost its Y chromosome entirely?

Two papers in Nature this April suggest we do not need to worry. At least when it comes to the primate lineage, it looks like the rot has stopped. Part of the reason may be that the Y chromosome carries genes that are not only crucial for sex determination, but individual survival. The findings also suggest men and women are more genetically different than we ever perceived in the past. “The dominant theory has been that hormones drive the difference: we want to shake that up and look at the genes,” says Daniel Bellott, research scientist at the Whitehead Institute at MIT and lead author of one of the Nature papers.

Decoding the Y has lagged way behind the other chromosomes. For one thing, after chopping it up into bite-sized bits to read its DNA sequence, it’s been hard to put back together. That’s because its DNA code is full of repetitive and inverted stanzas and researchers liken it to piecing together a jigsaw puzzle of blue sky.

And then there is the problem of testing what the Y genes do. Of all our genes, these are evolving at the fastest rate. So in many cases there are no equivalent genes in mice or fruit flies where their functions might be quickly tested. The current research, however, brings us a big step forward.

Thanks to nearly a decade of dogged puzzling, the two groups of researchers have now pieced together the Y chromosome in species from marsupials to humans. Working back from these species, the researchers can infer what the Y chromosome looked like in the common ancestor of mammals 180 million years ago. Unnervingly, the human Y appears to have lost 97% of the genes it once had. But the good news is that in the past 25 million years it has stabilised and some new genes have even been added.

Both groups found that marsupials and humans still share several related chunks of the Y, known as strata. Like the rock layers that tell the history of the Earth, these strata are key to understanding the evolution of the Y. The common ancestor of mammals had two X-like chromosomes. One of these acquired a masterful gene, known as SRY (sex-determining region Y), that took over from temperature to trigger male development. SRY’s job, then and now, is to switch on the gene circuit that directs the embryo tissue to form the testes. The default state is to develop as a female, but once you have testes all the rest follows – a penis, a male body, testosterone release at puberty and sperm production.

Once the ancestral mammal decided a sex-determining gene was a good idea, it was crucial to keep the SRY gene for the Y chromosome alone. Most chromosome partners engage in intimate gene swapping but this would be a singularly bad idea for SRY and its partner on the X, the SOX3 gene. The Y put a stop to gene-swapping by inverting the chunk that carried SRY. Since those chunks of the X and Y chromosomes were now back to front, they could no longer cosy up and swap genes. These inverted non-swappable bits of the Y-chromosome are the strata. (After doing it for SRY, other genes also turned out to be best kept for the Y alone.)

Strata are helpful for separating the sexes, but bad for the survival prospects of the genes on board. The genes can no longer swap faults with their partners on the X and so they start accruing mistakes that can never be corrected. Faulty genes are then jettisoned, explaining why the Y is down to 3% of its original cargo – now sitting at 30 genes.

Men and women aren’t just different when it comes to their sexual functions. Their brains are slightly different, as are their immune systems.

A handful of these are crucial for making a testis or for sperm fertility. But the authors wanted to know: what is special about the rest?

It turns out they may be crucial not for sex-related but for important “housekeeping” duties. When it comes to the chores for running a human body, the sex chromosomes are unusual. In each of our other 22 chromosomes pairs, each member of the pair carries equal weight. But in the case of the sex chromosomes, only one copy of an X is enough to do all the chores. Females put their second copy to sleep. And since males have only one X to begin with, the genders were thought to be equivalent in terms of their genes, except of course for the testis-determining and sperm-making genes. It turns out things are a little more complicated than that. For a handful of housekeeping genes, one active copy is not enough. So in females a few genes on the sleeping X must be roused for duty. And in males, some of the Y genes must pitch in to do some essential chores too.

Interestingly, genes in the male that have been recruited to help with the chores possibly do them slightly differently from their counterparts in the female. And that opens up some intriguing lines of inquiry.

Men and women aren’t just different when it comes to their sexual functions. Their brains are slightly different, as are their immune systems, so men are more predisposed to autism, and women to Graves disease. In Bellott’s view, the male housekeeping genes could be responsible. As one potential example he points to a Y gene called neuroligin 4 (NLGN 4) which could play a role in brain development. “It’s still a guess but it bears more looking into.”

Despite the hints that the Y is pulling its weight with the important chores, not everyone is convinced that that’s enough to secure its future. Jenny Graves, a marsupial geneticist at La Trobe University in Melbourne and a long-time defender of the rotting Y theory, points to the cautionary tales of the mole voles of Eastern Europe and the spiny rats of Japan. The rodents have completely lost their Y – yet they still produce males, presumably having transferred their genes for maleness to a different chromosome. “No matter how useful these Y-linked genes are, there is evidence the Y chromosome may be lost in the blink of an evolutionary eye,” she cautions.

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