The Quest For The "Y" Chromosome

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Scientists are close to deciphering the makeup of the Y chromosome, that essential core of maleness that's saddled with a bad reputation, a weird past and an uncertain future.

It's true, guys: Millions of years from now, your descendants might not have a Y chromosome at all.

But first things first. By this winter, scientists hope to have worked out the DNA sequence of the Y chromosome, the identity of its DNA building blocks. They plan to publish their analysis of the sequence sometime next year.

The work should help researchers learn about causes of male infertility, because it'll help them identify genes on the Y that men need to make sperm.

It should also give a big push to understanding the evolution and functions of the chromosome, a quest that went nowhere for decades until just the 1980s. In fact, one expert says earlier failures to understand the Y have given it a bad rap as a genetic couch potato, and he hopes new DNA studies will finally gain it some respect.

"There's been almost a century of ignorance-based misunderstanding of the Y," says David Page of the Whitehead Institute in Cambridge, Mass. "There aren't that many chromosomes that have an intellectual history" of thought and study by scientists, he said. "It's just that most of its intellectual history sounds like the life story of Rodney Dangerfield."

The Y chromosome probably didn't get much respect from your high school biology teacher. You did learn that chromosomes are the microscopic rods that hold genes. Chromosomes generally come in matched pairs, with one member of each pair from Mom and the other from Dad.

But men have one wildly mismatched pair, the X and the Y. The Y chromosome makes males. If you inherit it from your dad, you'll become a boy. If you get an X chromosome from Dad instead, you'll be a girl.

What else is there to say about the Y, this dinky chromosome with a paltry number of genes? Even now among scientists, Page concedes, beyond its sex-determining role "the general feeling is that it's at best a landfill."

But having studied it for about 20 years, Page sees it as more of a national park, full of unusual natural features.

"There's no doubt in my mind," he said, "that the Y will stand out as much as Yosemite and Yellowstone stand out from the landscape."

The sequencing of the Y is being overseen by Page and Robert Waterston and Rick Wilson of Washington University School of Medicine in St. Louis. The sequence will cover 20 million to 30 million of its 60 million building blocks, because the missing portion resists current sequencing technology and appears relatively inert anyway. Under scientific standards, the sequence will still be considered complete.

The effort is part of the Human Genome Project, which seeks to reveal the 3 billion chemical building blocks that make up all 24 of the human chromosomes. Only two chromosomes have been completely sequenced so far by the projet, which announced in June that it had finished a rough draft of all the human chromosomes.

Just this summer, Celera Genomics said it had sequenced all the human chromosomes, the collection called the human genome. But Celera shares its data only with paying clients. So for most scientists, data on the Y chromosome sequence will come from the efforts of Page, Waterston and Wilson.

By Malcolm Ritter
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