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Why, O Y? (Image: Alfred Pasieka/Getty)

The Y chromosome, which makes men male, has been shrinking for 180 million years. But there’s more to this rotting husk than anyone suspected

THERE’S nothing very macho about the Y chromosome. Even though it’s what makes men male, the human Y, like its counterparts in almost all mammals, is tiny compared with its partner, the X chromosome. It’s lost hundreds of genes – and if the Y continues to lose them, it could someday wink out of existence entirely.

Claims of its impending demise are starting to look premature, however. Far from being a rotting husk, the modern Y, tiny though it is, is turning out to be a highly evolved and surprisingly important part of men’s wider genetic endowment, responsible for far more than just maleness.

It is easy to see why some biologists thought the Y was destined for oblivion: it is all on its own. There are two copies of all other chromosomes, which are basically containers for holding genes. Each copy acts as a backup for the other. The pairs line up and swap bits when organisms reproduce. Some offspring get landed with chromosomes full of damaged genes and are eliminated by natural selection, whereas others inherit undamaged copies and survive to reproduce.

Way back in the evolutionary past, there was no Y, just a regular pair of chromosomes. Sex was determined by environmental factors such as temperature. But then a gene on a single chromosome mutated in a way that made any individual that inherited it male. At first this proto-Y could still swap genes with its partner, the proto-X chromosome. About 180 million years ago – in the line of mammals that branched away from the platypus and echidna – a section of it containing the gene variant for maleness got flipped back to front. This section no longer lined up properly with the corresponding part of the proto-X, so damaged genes in this section could no longer be swapped for good ones.

Beyond repair

Further inversions put more and more of the Y beyond repair. The X was fine because females inherit two copies that can swap parts. The Y, however, started to lose bits because men have just one copy. The human version now has just 78 genes, far less than its original 600 or so. At this rate of decay the Y ought to disappear altogether within 5 million years, as famously predicted a few years ago by Jenny Graves at La Trobe University in Melbourne, Australia.

“At this rate, it was famously predicted, the Y ought to disappear in 5 million years”

But there is growing reason to believe that what’s left of the Y is here to stay. For one thing, even though it has lost almost all of its original set of genes, it has gained others: we now know that 61 of the human Y’s 78 genes were not present before the first inversion took place. Almost all the new genes play a role in sperm production, making the Y a perfect home for them. There are often several copies of these genes, too, so there are backups.

An even stronger reason to think the Y chromosome has a bright future comes from the discovery, by Daniel Bellott at the Whitehead Institute in Boston, that its decay seems to have ground to a halt. His team compared the Y chromosomes of eight mammals – human, chimp, rhesus macaque, marmoset, mouse, rat, bull and opossum – to trace its evolutionary history (). They found bursts of gene loss directly after inversions happen, followed by long periods of stability. In fact, not a single gene has been lost from the oldest part of the human Y in the past 44 million years.

The remaining genes may simply be too essential to lose. A team led by Henrik Kaessmann at the University of Lausanne, Switzerland, surveyed the Y-chromosomes of 15 different mammal species and one bird. They found that a chromosome linked with maleness evolved three distinct times – once in birds, once in the ancestor of the platypus and echidna, and a third time in the ancestor of all other mammals. The ancestors of the three Ys each started with different kinds of genes, but to Kaessmann’s surprise, , which is what Bellott’s team also found. “You play this evolutionary game with different sets of genes, and you get the same kinds of genes retained in each case,” he says. “It’s always the regulatory genes that remain.”

Why? When a gene is lost from the Y, males are left with one copy of the gene, on their single X chromosome. That means less of the protein the gene codes for gets made – roughly half the usual dosage. Evolution can fix this in males by ramping up production from the single X, but then their female descendants get a double dose from their two Xs. To keep gene output the same in the two sexes despite this difference, females have evolved to inactivate one of their two copies of most genes on the X. Perhaps the amount of protein produced by the regulatory genes retained on the Y had to be so precisely calibrated that organisms couldn’t survive the awkward intermediate stage when this workaround did not yet function perfectly, suggests James Turner at the MRC National Institute for Medical Research in London. Regulatory genes are particularly vital because they control many other genes.

So important are the Y genes, in fact, that even during a man’s lifetime, losing the Y in some tissues takes a toll. Chromosomes can be lost when cells divide, and men who lose the Y chromosome in their bone marrow – which happens in about 8 per cent of elderly men – than other men.

Stable Y

All these findings seem to point in one direction. “The rotting-Y-chromosome theory is dead,” says Turner. Most people agree. Graves remains a holdout, however, noting that many of the genes Bellott and Kaessmann single out as essential on the human Y have disappeared from the Y of some other mammals, suggesting they are not so essential after all.

Nor is Graves reassured by the finding that the human Y has been stable. “Just the fact that we’ve had pretty much the same Y chromosome for millions of years doesn’t mean it won’t disappear tomorrow,” she says, pointing out that it already has in a few rodents, insects and other organisms.

Whatever the human Y chromosome’s ultimate fate, the new findings are raising interesting issues. Since the Y chromosome no longer interacts with the X, even the genes they still have in common have been evolving separately for tens of millions of years. So might they now play subtly different roles in the body? A Y-chromosome copy of a regulatory gene that turns on a slightly different set of genes in a slightly different group of cells than the X copy could make male and female cells act quite differently from each other. “This could have important consequences for differences in disease prevalence between males and females,” says Bellott.

Kaessmann agrees. “It’s going to be very interesting to find out what the Y genes might regulate, compared to the X copies,” he says. So not only is the Y chromosome no longer shrinking, it may be growing in importance – at least in the minds of biologists.

This article appeared in print under the headline “Why oh Y?”