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February 2012, Week 4

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Fri, 24 Feb 2012 23:37:42 -0500
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The Human Y Chromosome Is Here to Stay

     The male sex-determining chromosome has lost only
     one gene in 25 million years.

Ewen Callaway
22 February 2012
Nature
http://www.nature.com/news/the-human-y-chromosome-is-here-to-stay-1.10082

Men can breathe a sigh of relief - their sex-determining
chromosomes aren't going anywhere. A study of human and
rhesus monkey Y chromosomes questions the notion that
the Y is steadily shedding genes and is doomed to
degenerate.

In fact, the version of the Y chromosome that every
human male carries around has lost just a single gene in
the 25 million years since humans and rhesus macaques
shared a common ancestor.

"I think it should finally put an end to the speculation
about the demise of the Y. Twenty-five million years is
a big chunk of the history of the Y," says Jennifer
Hughes, a geneticist at the Whitehead Institute for
Biomedical Research in Cambridge, Massachusetts. She and
colleague David Page led the study, which is published
online today in Nature[1].

A brief history of Y

The Y chromosome emerged around 200 or 300 million years
ago, in a common ancestor of most mammals. Males and
females already existed, but their sex was determined by
environmental factors such as temperature, rather than
genetics.

This all changed when a gene called SRY evolved from a
related gene, SOX3. For reasons that scientists are
still studying, SRY, and not the environment, now made
males male. The chromosome on which SRY evolved became
the first Y, and its former pair, home to SOX3, became
the X chromosome.

Like normal pairs of chromosomes, or autosomes, the
early X and Y chromosomes reshuffled their genetic
material in each generation. Gradually the Y withered
away, losing hundreds of genes and most of its ability
to recombine with the X. The chromosomes now reshuffle
their DNA at the tips only.

In a 2002 article in Nature, two Australian scientists
examined the rate at which the Y has withered and
estimated that it "will self-destruct in around 10
million years"[2]. Some mammals, including mole voles and
spiny rats, have lost their Ys already, and sex-
determining genes have emerged on other chromosomes. It
seemed that this could be the destiny of the human Y.

Monkey business

Hughes, Page and their team published[3] the sequence of
the chimpanzee Y chromosome in 2010, and found vast
differences between it and the human Y. Chimpanzees have
shed many protein-coding genes in the roughly 6 million
years since their lineage diverged from that of humans.
But other parts of the chimp Y had been duplicated over
and over again in that time.

Hughes theorizes that the amplifications endowed chimps
with extra copies of genes involved in sperm production
- a useful trait for a promiscuous species in which
multiple males mate with fertile females. "If you have a
chromosome that is really good at making sperm, it might
not matter" that it has lost these other genes, she
says.

To gaze even further back into the history of the Y,
Hughes and her team decoded the Y chromosome of the
rhesus macaque (Macaca mulatta), which has a common
ancestor with humans and chimps that lived around 25
million years ago. Macaques are promiscuous, and Hughes
expected to see that the macaque Y had dropped some
genes and duplicated others involved in making sperm.

"It couldn't have been more different," she says. The
macaque Y contained just one gene that humans have lost,
and that gene resides on a particularly unstable portion
of the Y. The human Y has grown much longer than the
macaque's, but the genes were mostly the same.

"Those are the genes that give me confidence that in
another 50 million years, the Y chromosome will still be
there. They're not going away," says Scott Hawley, a
geneticist at the Stowers Institute for Medical Research
in Kansas City, Missouri. He suggests that the genes
have stuck around because, without them, men would be
infertile.

"I'm more worried about global warming than the Y
chromosome disappearing," says Hawley. "I'm hoping that
this paper has settled this controversy."

Jennifer Graves, a geneticist at La Trobe University in
Melbourne, Australia, and one of the scientists to
predict the demise of the human Y in the 2002 Nature
article, commends the new study, but she still questions
the Y's long-term prospects. The human version is full
of inverted DNA duplications containing both active and
broken genes. Graves considers these duplications to be
the chromosome's dying gasps.

"The Y could disappear tomorrow if another sex-
determining gene were to arise on an autosome," she
says.

Nature doi:10.1038/nature.2012.10082

References
[1] Hughes, J. F. et al. Nature
http://dx.doi.org/10.1038/nature10843 (2012).

[2] Aitken, R. J. & Graves, J. A. M. Nature 415, 963 (2002).

[3] Hughes, J. F. et al. Nature 463, 536-539 (2010).

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