No Y? No problem, apparently (Image: James Cavallini/SPL)

Being a male is easier than it looks. The defining genetic feature of maleness, the Y chromosome, contains only two genes that are absolutely essential for male function – at least in mice. The discovery may someday help develop new forms of assisted reproduction for infertile men.

Until recently, many geneticists thought of the Y chromosome as a vestigial ruin full of decaying genes and doomed to evolutionary oblivion because, unlike all the other chromosomes, it lacks a second copy to serve as a backup when mutation strikes. However, the Y turns out to have other ways of repairing mutations, and recent evidence suggests that the chromosome has been relatively stable over the last 100 million years of evolution. However, most of its genes are involved in a single function, male reproduction.

Researchers have known for more than two decades that a single gene on the Y chromosome, called Sry, is responsible for sex determination. Transgenic mice lacking a Y chromosome but with Sry inserted on another chromosome develop as males, though they can’t produce sperm. More recently, other researchers showed that the same mice could, in fact, produce immature sperm cells if they also inserted a second gene from the Y chromosome, Eif2s3y.


Y-less males

“This is where we came into the picture,” says Monika Ward, a reproductive biologist at the University of Hawaii in Honolulu. Ward and her colleagues had been developing methods for injecting immature sperm directly into the eggs. Would the technique work for the very immature sperm produced by Y-less “males” with only Sry and Eif2s3y?

Sure enough, when Ward’s team used a technique called round spermatid injection (ROSI) to insert the immature sperm into eggs, fertilisation was successful about 9 per cent of the time. That is a much lower success rate than the 26 per cent they see with normal, Y-bearing mice. Still, the offspring appeared to develop normally into healthy, fertile adults – evidence that just the two genes are enough to produce males that can reproduce, albeit with plenty of assistance.

That doesn’t mean that the rest of the Y is useless, Ward notes. The other genes it contains are important for production of fully mature, motile sperm capable of fertilising an egg in the normal way. “What we have achieved with only two genes is assisted fertilisation, which is a different story,” she says.

The picture is likely to be somewhat different in humans, since our Y chromosome lacks the Eif2s3y gene. However, a similar gene on another chromosome plays a role in some forms of male infertility. This raises the possibility that doctors might someday be able to encourage sperm precursor cells from these infertile men to develop far enough to be suitable for assisted reproduction, says Ward – though this has the drawback that any male children would carry the same genetic defect and thus require assisted reproduction themselves.

It is surprising that so few genes are essential, even for heavily assisted reproduction, says Michael Griswold, a reproductive biologist at Washington State University in Pullman, who calls Ward’s work “terrific”. “You’d think there would be more Y chromosome genes that would be necessary,” he says.

Journal reference: Science, DOI: 10.1126/science.1242544