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ENTER THE GENOME:
Y is for Guy

February 10, 2001

For scientists, the difference between the sexes comes down to one very small thing: the Y chromosome. Having a Y is what makes a guy a guy. Now researchers have published the first map of the Y chromosome in this week’s issue of Nature magazine. By deciphering its genes, they’ve learned just how this one unique chromosome is responsible for the difference between being a man or a woman, as well as its role in infertility.

Guy with a Y

"The Y chromosome is really quite unique within the human genome," says Dr. David Page, a member of the Whitehead Institute for Biomedical Research, whose Center for Genome Research is part of the International Human Genome Project. "It’s unique in two respects. One is, it’s the only chromosome that’s present in only one sex, but not both sexes…The second respect in which the Y is unusual is that it doesn’t have a partner with which it trades parts in the making of eggs and sperm."

Genetically speaking, men and women are really very much alike. The difference between them is that whereas women have two X chromosomes, men have an X and a Y. Scientists suspect, however, that 300 million years ago, the X and the Y were actually identical, an ordinary pair of non-sex chromosomes, according to Page.

But somewhere along the way, the Y lost probably 99 percent of its genes. "It is in that sense a rotted out X chromosome and it has just a tiny fraction of the genes that it once shared with the X," says Page. The genes that the Y still shares with the X are thought to hark back to their shared ancestry.

Researchers at Sanger Center
Researchers at the Sanger Centre
image: Wellcome Trust

This common heritage is the key to recessive diseases that are linked to the X chromosome and affect only males, such as hemophilia, Duchenne muscular dystrophy, or color blindness. "When we think about the Y chromosome we have to think about the X, and when we think about the X we have to think about the Y because they have this common ancestry," explains Page. Because males have only one X chromosome, if a gene on it is defective, it’s more likely to show up as a disease. "Girls have a backup copy, boys fly without a co-pilot on the X chromosome," says Page. "So in a sense the rotting out of the Y chromosome has created the X-linked recessive mode of inheritance that gives rise to all these diseases that are so much more common in boys than in girls."

While other chromosomes shuffle their genes regularly in a process called sexual recombination, the Y doesn’t. As a result, it can’t do a good job of maintaining the health of its genes as it evolves. "It’s like a house that can’t be properly maintained, so it slowly crumbles," says Page.

What a difference a gene makes

With all of these seeming weaknesses, the Y certainly knows how to do its job. After all, it is responsible for men being men. But perhaps not in the way that most people imagine. "There are all sorts of things that in popular cartoons have been attributed to the Y chromosome," says Page. "People talk about channel surfing and belching genes and all sorts of things like that on the Y chromosome." In reality, he says that the genes on the Y that have to do with the difference between males and females are mostly dedicated to sperm production.

Dr. David Page of the Whitehead Institute for Biomedical Research talks about the Y chromosome.

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Apparently at some point during evolution, a number of genes whose main job was the making of sperm migrated to the Y from other chromosomes. As a result, the Y ended up becoming very specialized in this one aspect of maleness. Page says that a sizable portion of male infertility can be traced to deletions on the Y chromosome. It was also found that fathers can pass infertility onto sons.

"Today, the Y chromosome looks like a very specialized entity and not many years ago it was thought that the Y was essentially a genetic wasteland that carried virtually no genes," says Page. Although scientists now know that the Y does carry genes, Page’s group found only a few dozen of them on the Y. But these are evidently enough to account for the difference between being male and female.

Or perhaps even one gene is enough. Page says that a gene on the Y chromosome called the SRY causes a human embryo to develop testes and become a male. If this gene isn’t there, the embryo will develop ovaries and become a female. "It’s quite interesting to think about the dramatic impact that one gene by its presence or absence has on each of our lives," he says.

Future Y

With its dynamic evolutionary history, Page says he can imagine three possible outcomes for the Y chromosome over the next hundred million years or so. One is that it could disappear, completely shrivel up and become unnecessary, as in the case of the nematode worm, which has an X but no Y chromosome.

Another possibility is that it could continue its present course of incorporating a select few new genes from other chromosomes—such as the sperm producing genes it already recruited—thereby making it indispensable. Yet another scenario is that both the X and the Y could both become very large by taking on genetic material from the other chromosomes, until they essentially absorb the rest of the genome.

We won’t be around to see which of these scenarios plays out, but in the meantime, scientists are keeping busy by trying to answer questions about the Y chromosome in its present evolutionary state. One of the most intriguing is whether the Y’s role in maleness is really limited to genes that produce the necessary physical equipment. "Could there be more to it?" wonders Page. "Could the Y for instance play a role in the differences between the brains of males and females? We don’t have any evidence to suggest that at present, but it remains an interesting possibility."



by Jill Max


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