THE genetic sequence of the human Y chromosome has been published, unveiling surprises that will advance research on fertility, rekindle debates on the evolution of the sexes and challenge the controversial idea that the Y chromosome is a genetic junkyard destined for extinction.
The male-determining Y has been considered a vestigial chromosome with a tiny, ever-dwindling collection of about 40 genes. The reason for the genetic attrition, scientists thought, was Y鈥檚 inability to pair and swap genetic material with other chromosomes. That takes place during a process called crossing-over, which is key to repairing genetic mutations and preserving genes.
Because Y can鈥檛 repair itself, the idea went, its genes have slowly disappeared over time. Controversially, some scientists believe they might all wither away within 5 million years (快猫短视频, 24 August 2002, p 29).
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But now David Page and his team at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and Washington University School of Medicine in St Louis, Missouri, have found evidence suggesting the Y chromosome is mightier than we gave it credit for, containing about 78 genes. 鈥淚f the Y is a corpse, we better start seeing it as a vampire, because it鈥檚 really alive,鈥� says Scott Hawley of the Stowers Institute for Medical Research in Kansas City.
The researchers discovered that a portion of genes, especially those essential for male fertility, lie in complex regions of the Y chromosome that are mirror images of each other and repetitive in nature. That unique arrangement allows the genes to pair up, repairing each other in a process called gene conversion, which is related to crossing-over. 鈥淪o [the Y] has a mechanism to correct itself,鈥� says Hawley. 鈥淎ll of a sudden, you have a powerful selective force to maintain the chromosome.鈥�
Page suggests that gene conversion in that portion of the Y is as frequent as crossing over in regular chromosomes. A Y passed down from father to son will have about 600 base pairs overwritten, and hence repaired, within just that one generation.
Humans are the first species to have their Y chromosome sequenced in such detail, and the results mark the culmination of decades of research (Nature, vol 423, p 825 and p 873). Figuring out a way to sequence the intricate structure of the Y is a major achievement in itself, as it is laden with repetitive genetic sequences called amplicons. Only by accurately sequencing each amplicon can researchers distinguish one from another 鈥� a laborious process that wasn鈥檛 used in sequencing much of the human genome.
The work is already increasing our understanding of the causes of male infertility. It turns out many men are infertile due to deletions of the mirror-image regions of their Y chromosome 鈥� the same regions that undergo gene conversion. Ironically, the very areas of the Y that help it save its genes from annihilation are especially susceptible 鈥� due to their repetitive nature 鈥� to deleting themselves in individuals, says Page.
The revelation that the Y chromosome may carry important genes could shatter the conventional wisdom that many differences between males and females in susceptibility to disease 鈥� such as women鈥檚 higher likelihood of getting autoimmune disease 鈥� are due to differences in sex hormones. Instead, genes on the Y chromosome, which women lack, could be responsible. 鈥淣ow we know there are a lot of genes on the Y, we have to go back to square one,鈥� says Page.
