Washington, USA
- The Y chromosome -- widely thought of as the seed
of manliness and a stretch of DNA containing few
functioning genes -- is relatively full of genes,
researchers reported here Wednesday.
The findings may shed
light on mutations that can lead to infertility, but
won't do much to explain the mysteries of male behavior,
researchers said.
While women usually have
two X chromosomes, men typically have an X and a
Y.
Scientists from the
Whitehead Institute for Biomedical Research
<http://www.wi.mit.edu/>
in Cambridge, Massachusetts, and the Washington
University School of Medicine <http://medschool.wustl.edu/>
in St. Louis unveiled their complete sequencing and
analysis of a section of the Y chromosome, which they
have dubbed the male-specific region of the Y, or the
MSY.
The tips of the Y had
already been sequenced and analyzed. The Whitehead and
Washington University work is reported in two papers in
the June 19th issue of the journal Nature
<http://www.nature.com/nature/>.
Francis Collins, director
of the National Human Genome Research Institute (NHGRI)
<http://www.genome.gov/>,
said the Y has long been considered the "Rodney
Dangerfield of all chromosomes."
But, he added, "the
analysis has revealed some surprising insights." The
NHGRI supported the research.
Senior investigator David
Page of Whitehead agreed with Collins that the Y has
gotten no respect, and said that just last year, a
Nature editorial prophesied that the chromosome
would be extinct in about 10 million years.
"We're here this morning
to defend the honor of the Y chromosome in the face of a
century of insults," said Page.
About 95 percent of the Y
consists of repetitive sequences. That identicalness
stymied previous efforts to map the area. But Page and
his colleagues painstakingly analyzed these "amplicons,"
and their work paid off with new discoveries.
Commenting in
Nature, Huntington Willard of Duke University's
Institute for Genome Science and Policy
<http://www.genome.duke.edu/research/centers/gelp/>
said their work shows that "even the most repetitive and
seemingly impenetrable stretches of the genome hold
secrets that justify the effort."
It has long been thought
that since the Y does not have much cross-over with the X
chromosome -- unlike other pairs of chromosomes that swap
information when egg and sperm meet -- that it has a long
stretch that is vulnerable to mutation, and thus,
eventual death.
"The Y has essentially
been viewed as a bumbling chromosome that is unable to
repair itself," said Page. But he and his colleagues
found that the highly repetitive string of sequences, the
MSY, actually contains eight massive palindromes --
sequences that read the same both forwards and backwards.
Those palindromes, formerly thought to be the genetic
equivalent of a wasteland, actually contain most of the
genes on the Y, and allow for swapping of DNA within the
Y, said Page.
In that way, the Y
repairs any mutations. Each male newborn undergoes an
estimated 600 changes in DNA base pairs in an effort to
overwrite any mutations, reports Page's colleague Steve
Rozen, lead author on the paper attempting to explain the
Y's recombination process. It seems that the repetitive
sequences swap between the two arms of the Y, leaving a
son's Y chromosome different from his
father's.
But the survival strategy
may also leave the Y vulnerable to deletions that lead to
infertility.
It has been known since
the mid-1970s that deletions in the Y are the most common
cause of male infertility. Page and his colleagues are
adding to that knowledge, having found that of the 78
genes in the MSY, 60 are active mainly in the testis, and
are involved in spermatogenesis.
Women hoping that the Y
analysis would lead to easy explanations of male behavior
will be disappointed, said Page. But, he added, it is
possible that future scrutiny of the chromosome may turn
up more genes or better-defined functions of the known
genes.
"It easily could play a
role in differences in disease susceptibility between men
and women," he said.
