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Y chromosomes evolving rapidly 2010.01.14

By comparing human and chimpanzee Y chromosome sequences, Whitehead Institute geneticists show the Y is undergoing swift change.

The Y chromosome, right, is dwarfed by the much larger X chromosome.
Photo: MITnews
 
January 14, 2010

Massachusetts Institute of Technology

The Y chromosome is often considered somewhat of a genetic oddball.
Short and stubby, it carries hardly any genes, most of which are related to traits associated with maleness.
Most of the chromosome consists of highly repetitive sequences of DNA, known as massive palindrome sequences, whose function is unknown.

 
   
 
Evolutionary biologists have long believed that the mammalian Y chromosome is essentially stagnant, having lost most of its genes hundreds of millions of years ago. But new research from MIT's Whitehead Institute, published in this week's issue of Nature, overturns that theory.
The research team, led by Whitehead Institute director and MIT biology professor David Page, showed that the Y chromosome is actually evolving rapidly and continuously remaking itself.

For the first time, the researchers sequenced the Y chromosome of the chimpanzee, allowing for the first interspecies comparison of the chromosome.
They found significant differences between the two species' Y chromosomes, suggesting that those chromosomes have evolved faster than other chromosomes during the six million years since humans and chimpanzees emerged from a common ancestor.

The findings offer the first evidence that a Y chromosome as evolutionarily old as the human Y is in fact still evolving, says Andrew Clark, a genetics professor at Cornell University who studies Y chromosome evolution in fruit flies.

"There's a dramatic amount of turnover, and it's not just degeneration — it's gain and loss of genes that do something on the Y chromosome," says Clark, adding that the new sequence comparison may also help researchers study male infertility, which is often driven by defects in the Y chromosome.

Hundreds of millions of years ago, the Y diverged from its sister X chromosome and became specialized for male-specific traits.
Evolutionary biologists have theorized that it quickly lost most of its genes through a process known as degeneration, then lapsed into a fairly static state.

However, this theory was difficult to test because all of those repetitive DNA stretches make the Y chromosome very tricky to sequence, says Jennifer Hughes, a postdoctoral associate at the Whitehead Institute and lead author of the Nature paper.
Most genome sequencing studies completely exclude the Y chromosome.

In 2003, Page's laboratory and collaborators at the Genome Center at Washington University (who were also involved in the new chimpanzee study) were the first team to sequence the human Y chromosome.
They found that the Y carries 78 genes, more than expected, but still far fewer than the 1,000 or so located on the X chromosome.

"Having the human sequence tells us quite a bit, but to obtain information about the evolution of the Y, we needed to do a comparative analysis," says Hughes.

As its next target, the Whitehead team chose the chimpanzee, humans' closest living relative.
Human and chimpanzees genomes differ very little: 98.8 percent of DNA base pairs are identical between the two species.

Page's team expected that the chimpanzee and human Y chromosomes would also be very similar.
To their surprise, they found that chimp and human Y chromosomes differ considerably — far more than the rest of the chromosomes.
During the six million years of separation, the chimp Y has lost one-third to one-half of the human Y chromosome genes.
However, the chimp Y has twice as many massive palindrome sequences as the human Y.

Page compares the Y chromosome changes to a home undergoing continual renovation.
"People are living in the house, but there's always some room that's being demolished and reconstructed," says Page, who is also a Howard Hughes Medical Institute investigator.
"And this is not the norm for the genome as a whole."

The researchers suspect several factors are at play in the divergent evolution of human and chimp Y chromosomes, including differences in mating behaviors. Because a female chimpanzee may mate with many male chimpanzees around the same time, any genes on the Y chromosome that lead to enhanced sperm production offer a distinct competitive advantage.

If a Y chromosome with genes for enhanced sperm production also carries mutations that alter or eliminate a gene not related to sperm production, those less advantageous mutations also get passed on, resulting in a Y chromosome with far fewer genes than the human Y.

"The gene loss seen in chimps and the possibility that this has been driven by the influence of sperm competition in chimps but not humans is interesting, and we will be able to judge this more readily once we have functional information about the gene products, which is still sketchy in many cases," says Mark Jobling, professor of genetics at the University of Leicester, who studies the evolution of the Y chromosome.

Researchers in the Page lab and the Washington University Genome Center are now sequencing and examining the Y chromosomes of several other mammals, to investigate whether rapid evolution is occurring in species other than humans and chimpanzees.


Anne Trafton

MIT News Office

http://web.mit.edu/newsoffice/2010/y-chromosome-0114.html  



ASTROMAN magazine


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