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What do a trout, sea anemone, rooster, fly and man
have in common? 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."
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.
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.
Xu is senior author of a paper on the study that
will be published July 15 in PLoS Genetics.
For more information
http://www.northwestern.edu/
(MDN)
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