Y chromosome uses trick to repair its own most crucial genes, analysis finds

Wednesday, June 18th 2003, 12:00 am
By: News On 6

Scientists have discovered that the Y chromosome uses a neat trick to repair its most crucial genes, a strategy that apparently helps keep it from rotting away over evolutionary time.

The Y chromosome, of course, is best known for supplying the biological signal that makes males rather than females.

Some scientists have it might disappear millions of years from now because it can't eliminate genetic defects in the usual way, and broken genes tend to erode away over the long haul.

But there are reasons to be optimistic about the chromosome's future, and the new work adds one more.

``Y chromosomes really have a big trick up their sleeves,'' said David Page, a Howard Hughes Medical Institute investigator at the Whitehead Institute for Biomedical Research in Cambridge, Mass.

The gene-fixing trick was already known to happen occasionally in human DNA, but the surprise is that the Y chromosome has elevated it to standard operating procedure, said Page, who led the research.

The work by scientists at the Whitehead and the Washington University School of Medicine in St. Louis appears in Thursday's issue of the journal Nature. It's the first comprehensive and detailed analysis of the genetic code of the Y chromosome, which is best known for supplying the signal to make males.

The work is ``a landmark for the history of sex determination,'' declared Dr. Francis S. Collins, director of the National Human Genome Research Institute.

Scientists said followup work could illuminate basic biological differences between the sexes, perhaps shedding light on causes of differences in disease susceptibility, for example.

The Y chromosome can't fix its genes in the usual way because it doesn't meet up with other Y chromosomes. The body's other chromosomes are inherited in pairs, with one member coming from a mother and the other from a father. That pairing lets them swap corresponding pieces of themselves, a mechanism that lets the species get rid of damaged genes.

But the Y chromosome comes by itself. It can't trade appreciable amounts of DNA with its partner, the X chromosome, so it can't get rid of damaged genes that way.

The new work reports evidence that the Y chromosome makes extensive use of a process called gene conversion. The chromosome carries backup copies of its important genes, and it can use one copy to fix a flaw in the other.

Page said the gene-fixing technique comes at a price. When the chromosome makes a mistake in the procedure, it can delete stretches of DNA. Such deletions, occuring in one in every couple thousand boys, are a recognized cause of male infertility.

Huntington Willard, director of the Institute for Genome Sciences and Policy at Duke University, said the new work provided the clearest demonstration in human DNA of the gene-fixing process at work.