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November 12, 2009

Speech Gene Shows Its Bossy Nature

By NICHOLAS WADE

Of the 20,000 genes in the human genome, few are more fascinating than FOXP2, a gene that underlies
the faculty of human speech.

All animals have an FOXP2 gene, but the human version’s product differs at just 2 of its 740 units from
that of chimpanzees, suggesting that this tiny evolutionary fix may hold the key to why people can speak
and chimps cannot.

FOXP2 came to light in a large London family, half of whose members have severe problems in articulating
and understanding speech. All turned out to have a mutation that disrupted this vital gene.

This year, one inquiry bore fruit, although of a somewhat ambiguous nature, when biologists in Leipzig,
Germany, genetically engineered a mouse with the human version of FOXP2 substituted for its own. The
upgraded mice squeaked somewhat differently from plain mice and were born with subtle alterations in
brain structure. But mice and people are rather distant cousins — their last common ancestor lived some 70
million years ago — and the human version of FOXP2 evidently was not able to exert a transformative effect
on the mouse.

A scientific team led by Dr. Daniel H. Geschwind of the University of California, Los Angeles, has now
completed a parallel experiment, which is to put the chimp version of FOXP2 into human neurons and see
what happens. These were neurons living in laboratory glassware, not a human brain, so they gave a
snapshot of FOXP2 only at the cellular level. But they confirmed suspicions that FOXP2 was a maestro of
the genome.

The gene does not do a single thing but rather controls the activity of at least 116 other genes, Dr.
Geschwind’s team says in the Thursday issue of Nature.

Like the conductor of an orchestra, the gene quiets the activity of some and summons a crescendo from
others. Surprisingly, the chimp version of the gene had a more forceful effect in the human nerve cells than
did the human version.

“The human FOXP2 seems to be acting on a more refined set of genes,” Dr. Geschwind said in an interview
from London.

Several of the genes under FOXP2’s thumb show signs of having faced recent evolutionary pressure,

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FOXP2 Speech Gene Shows Its Bossy Nature - NYTimes.com

meaning they were favored by natural selection. This suggests that the whole network of genes has evolved
together in making language and speech a human faculty.

And some of the genes in FOXP2’s network have already been implicated in diseases that include disorders
of speech, confirming its importance in these faculties.

But the FOXP2 network is certainly not the only set of genes involved in language. For one thing, FOXP2 is
equally active on both sides of the human brain, whereas the language faculty is asymmetric, Dr.
Geschwind said.

By studying the other genes in the FOXP2 network, Dr. Geschwind said, he hoped “to use FOXP2 as a lever
to get a view of the molecular machinery in a biological language circuit.”

In a commentary on the new finding, Martin Dominguez and Dr. Pasko Rakic of Yale describe it as an
important discovery that “provides a starting point for future studies of the molecular basis of language and
human evolution.”

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