http://www.sciencedaily.com/releases/2010/07/100715172000.htm

Human Sperm Gene Is 600 Million Years Old, Scientists Discover

ScienceDaily (July 15, 2010) — Just as styles in sexy clothes or
fashion change from year to year and culture to culture, "sexy" genes,
or genes specific to sex, also change rapidly. But there is one
sex-specific gene so vital, its function has remained unaltered
throughout evolution and is found in almost all animals, according to
new research from Northwestern University Feinberg School of Medicine.

The gene, called Boule, is responsible for sperm production.
Northwestern scientists also discovered in their research that Boule
appears to be the only gene known to be exclusively required for sperm
production from an insect to a mammal.

"This is the first clear evidence that suggests our ability to produce
sperm is very ancient, probably originating at the dawn of animal
evolution 600 million years ago," said Eugene Xu, assistant professor
of obstetrics and gynecology at Feinberg. "This finding suggests that
all animal sperm production likely comes from a common prototype."

Xu is senior author of a paper on the study that will be published
July 15 in PLoS Genetics.

The discovery of Boule's key role in perpetuating animal species
offers a better understanding of male infertility, a potential target
for a male contraceptive drug and a new direction for future
development of pesticides or medicine against infectious parasites or
carriers of germs.

"Our findings also show that humans, despite how complex we are,
across the evolutionary lines all the way to flies, which are very
simple, still have one fundamental element that's shared," Xu said.

"It's really surprising because sperm production gets pounded by
natural selection," he said. "It tends to change due to strong
selective pressures for sperm-specific genes to evolve. There is extra
pressure to be a super male to improve reproductive success. This is
the one sex-specific element that didn't change across species. This
must be so important that it can't change."

Boule is likely the oldest human sperm-specific gene ever discovered,
Xu said. He originally discovered the human gene in 2001.

Prior to the new findings, it was not known whether sperm produced by
various animal species came from the same prototype. Birds and insects
both fly, for example, but the fly wing and bird wing originated
completely independently.

For the study, Xu searched for and discovered the presence of the
Boule gene in sperm across different evolutionary lines: human,
mammal, fish, insect, worm and marine invertebrate.

In order to search for Boule's presence across the spectrum of
evolutionary development, Xu had an interesting shopping list. He
needed sperm from a sea urchin, a rooster, a fruit fly, a human and a
fish. The fish proved to be the most difficult.

Xu purchased a rainbow trout at a Chicago fish market, unwrapped it
and was dismayed to discover it had been gutted. "I need the
testicles!" he exclaimed to the seafood salesman. Xu decided he'd have
to catch his own. He cast a fishing line into a recreational pond
stocked with trout and reeled in a rainbow trout.

Discovery of this common gene involved in sperm production could have
many practical uses for human health, including male contraception.
When Xu's research group knocked out the Boule gene from a mouse, the
animal appeared to be healthy but did not produce sperm.

"A sperm-specific gene like Boule is an ideal target for a male
contraceptive drug," Xu noted.

Boule also has the potential to reduce diseases caused by mosquitoes
and parasites such as worms.

"We now have one strong candidate to target for controlling their
breeding," Xu said. "Our work suggests that disrupting the function of
Boule in animals most likely will disrupt their breeding and put the
threatening parasites or germs under control. This could represent a
new direction in our future development of pesticides or medicine
against infectious parasites or carriers of germs."

To further support his hypothesis that Boule is widespread across all
animals producing sperm and eggs, Xu also examined the genome of one
of the most primitive animals, a sea anemone, for the presence of
Boule. He looked at its genome because the sperm of the sea anemone is
difficult to find and few labs study the animal. When Xu identified
Boule in the sea anemone genome, his theory was clinched.

Xu's co-authors, all past or present members of his lab, include
Chirag Shah, Michael VanGompel, Villian Naeem, Yanmei Chen, Terrance
Lee, Nicholas Angeloni and Yin Wang.

Xu's research was supported by the National Institutes of Health and
Northwestern Memorial Foundation.


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