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A Bird "Language" Gene Pinpointed

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Duke Health News 919-660-1306

DURHAM, N.C. -- Neurobiologists have discovered that a
nearly identical version of a gene whose mutation produces an
inherited language deficit in humans is a key component of the
song-learning machinery in birds.

The researchers, who published their findings in the March
31, 2004, issue of the Journal of Neuroscience, said
that their finding will aid research on how genes contribute to
the architecture and function of brain circuitry for singing in
birds.

Among the lead researchers was neurobiologist Erich Jarvis,
Ph.D., of Duke University Medical Center and Constance Scharff
of the Max Planck Institute for Molecular Genetics in Germany.
Co-first authors of the paper were Sebastian Haesler of the Max
Planck Institute and Kazuhiro Wada, M.D., of Duke. Other
authors were Edward Morrissey of the University of Pennsylvania
and Thierry Lints of the City College of New York. The work was
supported by the U.S. National Science Foundation and the
German Research Foundation.

According to Jarvis, the search for the gene, called FoxP2,
began when other researchers reported that the human version of
the gene was responsible for a deficit in language production
in humans.

"In affected humans, the mutation causes a very specific
dysfunction," said Jarvis. "These people have largely normal
motor coordination, but an inability to correctly pronounce
words or form them into grammatically correct sentences. What's
more, they have trouble understanding complex language."

When evolutionary geneticists compared the DNA sequence of
the normal human FoxP2 gene with nonhuman primates and other
species, they found that humans have a specific sequence
variation not found in any other mammal, said Jarvis.

"Thus, since birdsong is a learned vocal behavior like
speech, we decided to find out if a version with this same
variation was present in vocal-learning birds," said
Jarvis.

Particularly significant, he said, is that the human version
of FoxP2 is a type of gene that regulates many other genes --
thus making it an ideal candidate for a gene in which a single
change during evolution could create a cascade of changes that
would influence an advance such as speech or birdsong.

"One advantage of using vocal learning birds," said Wada,
"is that there are thousands of songbird species and several
hundred parrot and hummingbird species that have vocal
learning, but only one primate species that has vocal learning,
us humans. Thus, vocal-learning birds provide a rich source of
material for evolutionary comparisons."

In their studies, Jarvis and Wada at Duke, and Scharff and
Haesler in Germany, compared brain expression of the FoxP2 gene
in birds that are vocal learners with those that are
nonlearners. Vocal learners included species of finches, song
sparrows, canaries, black-capped chickadees, parakeets and
hummingbirds. A vocal nonlearner included ring doves; and the
researchers also studied the gene in crocodiles, the closest
living relative to birds.

Specifically, they sought to measure where and when the
FoxP2 gene was expressed in the brains of birds; whether the
gene was expressed in song-production and song learning areas
of the brain, and whether it was expressed more actively during
times of song learning or production.

The teams also analyzed the structure of the songbird FoxP2
gene and compared it with the human gene.

Researchers in another laboratory headed by Stephanie White
at UCLA published a paper in the same issue of the Journal of
Neuroscience comparing the expression of FoxP2 and its close
relative FoxP1 in songbirds and humans.

Scharff, Jarvis and their colleagues confirmed that all the
non-mammals they studied, including crocodiles, did have a
FoxP2 gene. And although the genes in humans and song-learning
birds were almost identical (98 percent), the song-learning
birds did not have the specific variation characteristic of
humans.

"Thus, this human-specific mutation is not necessarily
required for vocal learning, at least not in birds," said
Jarvis. "Or perhaps there's another variation in the songbird
gene that also leads to vocal learning."

The researchers did find that the FoxP2 gene was expressed
in the same area of the brain -- called the basal ganglia -- in
both humans and song-learning birds. And most importantly, the
researchers found the FoxP2 gene to be expressed at higher
levels in the "vocal learning nucleus of the basal ganglia of
song-learners" at times during the bird's life when it is
learning song. This critical learning time might either be
during early development in the case of zebra finches, or
during seasonal changes in song learning, as in canaries.

"We found that the levels of FoxP2 seem to be increasing at
times just before the bird begins to change its songs," said
Jarvis. "So, this is consistent with a cause-and-effect role,
in which the gene switches on, allowing the song-learning
circuitry to become more plastic, which allows the birds to
imitate sounds."

"By contrast, when we analyzed the non-vocal-learning
species, we did not see this localization or difference in
level of FoxP2," said Jarvis.

Jarvis and Scharff are now completing a related study about
the precise variation in FoxP2 between vocal learning and
nonlearning birds, to pinpoint whether there are sequence
changes between birds that learn to sing and those that don't
-- analogous to the differences between humans and chimps. They
will also further explore the molecular signaling pathway
involving FoxP2, and attempt to alter the gene in birds to
explore how mutations affect vocal learning.

Jarvis emphasized that the discovery of FoxP2 represents
only the beginning of a major effort to explore the genetic
machinery underlying vocal learning and cautions that it has
not been proven that FoxP2 is required for vocal learning.

"We definitely don't think that FoxP2 is the single causal
gene for vocal learning," he said. "The difference between
vocal learners and nonlearners -- whether between humans and
nonhuman primates; or between learning and nonlearning birds --
is most likely to arise in connections of forebrain areas to
motor neurons that control the voice. It is intriguing though
that an ancient gene like FoxP2 appears to have something to do
with learned vocalizations both in humans and in birds.

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