A rat without a Y chromosome could be a glimpse of our genetic future

A rat without a Y chromosome could be a glimpse of our genetic future

The spiny rat Amami

The spiny rat Amami

ASATO KUROIWA

For any mammal, the loss of the Y chromosome should mean the loss of the males and the disappearance of the species. So how the spiny rat Amami copes without a Y chromosome has puzzled biologists for decades. Now, Asato Kuroiwa from Hokkaido University in Japan and his colleagues have shown that one of the normal rat chromosomes has indeed evolved into a new male sex chromosome.

The Y chromosomes of many mammals, including us, have shrunk over tens of millions of years and could eventually disappear, Kuroiwa says. The prickly rat shows how this could happen, she says.

There are many different sex determination systems in the animal kingdom, but in virtually all mammals, sex depends on the X and Y chromosomes. If an embryo inherits two X chromosomes, it develops into a female. If he inherits an X and a Y, he becomes male.

This happens because the Y chromosome contains a gene called SRY which activates “male” genes on other chromosomes – the most important SOX9 Gene that triggers testicular development.

The spiny rat Amami (Tokudaia osimensis), found on the Japanese island of Amami ƌshima, is one of the few mammals that lacks Y chromosomes. Additionally, both females and males have only one X chromosome.

As the existence of female mammals shows, the shrunken Y does not contain any crucial genes, so cells and individuals can survive its loss. In fact, recent studies show that cells are often lost as men age. But the loss of the Y of an entire population should lead to extinction, because there would be no more males.

To find out how male spiny rats still exist, Kuroiwa and his team first sequenced the genomes of several males and females, but found no variants unique to males. They then took a closer look and found that in male rats, one of the two copies of chromosome 3 has a duplicated region, right next to SOX9.

The team did a number of experiments – including adding the duplicated region to mice – to show that this duplication stimulates the activity of SOX9 and thus effectively replaces SRY. This means that chromosome 3 with the duplication has become a “proto-Y”, while the version without the duplication is a “proto-X”.

To demonstrate this beyond doubt, the team would have to remove the duplication in spiny rats to show that no male develops, says Robin Lovell-Badge of the Francis Crick Institute in London, one of the researchers who discovered the SRY embarrassed. Such experiments cannot be done because the spiny rat is an endangered species. “However, the evidence they have is all pretty compelling,” he says.

Duplications of this type, known as copy number variations, are difficult to spot, which would explain why previous attempts to discover how male spiny rats became males have failed.

The duplication must have occurred 2 million years ago, as that is when spiny rats diverged from related species that still have a Y chromosome. Once the duplication is present, the loss of the Y chromosome would no longer result in the loss of all males. Kuroiwa thinks that, for a time, a mixed population of men with and without Y was probably present on the island.

Then most of the individuals died, probably due to rising seas, leaving only males without Y. “At some point in the past the sea level rose and the land area was much more small,” says Kuroiwa.

“I think it’s brilliant work. The evidence is very compelling,” says Jenny Graves of La Trobe University in Melbourne, Australia, who in 2002 argued controversially that the human Y chromosome will eventually disappear in about 10 million years. “There is no reason to think that our Y chromosome is more robust than that of the spiny rat,” she says.

“I absolutely agree with Jenny,” says Kuroiwa. “I also believe that the Y chromosome will disappear.”

But Lovell-Badge points to a number of studies suggesting that the Y chromosome is fine and not at risk of being lost by us or other mammals. “I think the paper makes it pretty clear that the loss of a Y chromosome in mammalian evolution is a very rare event,” he says.

Since both sexes of the Amami spiny rat now only have one X chromosome, this could also be lost over time. “Since it’s unstable and the mutations accumulate, I think X will eventually die out,” Kuroiwa says.

However, if descendants of the spiny rat Amami survive long enough, its proto-X and proto-Y chromosomes are likely to evolve in the same direction as the X and Y, with the proto-Y shrinking and distinguishing itself from the proto-X .

Journal reference: PNASDOI: 10.1073/pnas.2211574119

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