Y chromosome sequence completed

JOHN WHITFIELD

The Y chromosome has sex with itself to guard against mutation. © GettyImages

Reports of the demise of the Y chromosome and an impending extinction of men may have been exaggerated. The Y's full genome sequence reveals that we have underestimated its powers of self-preservation.

Instead of doubling up to protect its genetic cargo like other chromosomes, the lone Y safeguards its genes by having sex with itself, an international consortium has found.

"We're on a quest to bring respectability to the Y chromosome," says geneticist David Page of the Massachusetts Institute of Technology, leader of the sequencing team. The male-defining chromosome was previously thought of as a wasteland where genes go to die.

The Y's defences are double-edged, however, sometimes leading to infertility. The sequence should help us to diagnose and treat such genetic mishaps.

Two-way street

Human chromosome pairs swap genes to minimize bad mutations. Y, which has no partner, faces being whittled away by mutation. Some estimate that the chromosome could be complete junk in about ten million years.

The finished sequence shows that the chromosome fights entropy with palindromes. About six million of its 50 million DNA letters reside in sequences that read the same, in opposite directions, on both strands of the double helix. The longest is nearly three million letters long¹. "The Y chromosome is a hall of mirrors," says Page.

These palindromes house many genes - which means that there is a copy at each end of the palindromic sequence. These provide back-ups should harmful mutations arise. The mirror-image structure also allows the arms to swap position when DNA divides. Genes are shuffled and bad copies are purged.

There are 50 million letters in Y's finished sequence. source: Nature

Page's team has calculated the amount of swapping needed in each generation to produce the near-perfect palindromes of the human Y. They estimate that every man's Y contains 600 DNA letters that differ from his father's². This is thousands of times more than the normal mutation rate.

"No one had contemplated that there would be this level of gene conversion in our own genome," says Huntington Willard of Duke University, Durham, North Carolina. "It gives us a glimpse of how the Y has protected itself."

Other researchers see swapping as an evolutionary accident, not a safeguard. "It's a daring suggestion, but I find it a bit difficult to believe," says geneticist Mark Jobling of the University of Leicester, UK.

Jobling is sceptical because the trick has a high cost: good genes are just as liable to be lost as bad. This is a major cause of male infertility, as most of the genes within the palindromes control testes development. One in every few thousand men is infertile because key genes have been deleted.

Y files

Genetic testing is already used to diagnose male infertility. A fuller understanding of the Y's make-up will help refine these tests, and improve doctors' advice to couples. "We have a greater knowledge of where the Y tends to break," says Page. "Testing needs to be updated to reflect our better understanding from the finished sequence."

The palindromes, and other forms of repeated DNA, made the Y chromosome very tricky to sequence. So the finished sequence comes from just one man's Y. Getting more sequences is essential, says Jobling, as the chromosome's structure, and hence biology, varies greatly around the world.

"We have a beautiful snapshot of the Y chromosome," he says. "Now we need to look in other lineages to build up a photo album of its diversity."

1. Skaletsky, H. et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature, 423, 825 - 837, (2003). |Article|
2. Rozen, S. et al. Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature, 423, 873 - 876, (2003). |Article|

© Nature News Service / Macmillan Magazines Ltd 2003