Life

It is often thought of as one of the things that make humans unique. Now, researchers are uncovering the suite of genes that gave us our gift of the gab.

All of them appear to be controlled by a master-switch gene called Foxp2. When inactive, this gene causes severe speech and language problems in humans. Although other animals have versions of Foxp2, in 2002 a German team identified two small alterations in the protein the human Foxp2 produces that are not carried by our closest living relative, the chimpanzee. This suggested that the human version of Foxp2 may function differently, and be a key element in our unique linguistic abilities.

Earlier this year, Wolfgang Enard's team at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, spliced this human version of Foxp2 into mice. The mice didn't start speaking, but their sub-sonic vocaliszations changed, as did the shape and activity of neurons in a brain area that goes awry in people with Foxp2-related language disorders.

To discover what Foxp2 does differently in humans, neuroscientists Genevieve Konopka and Daniel Geschwind at the University of California, Los Angeles, grew human brain cells lacking Foxp2 in Petri dishes. To some they added human Foxp2 and to others the chimp version. They then recorded all the genes that were affected. Out of the hundreds of genes controlled by Foxp2, they identified 116 that responded differently to the human version of Foxp2.

This set of genes fits well with Foxp2's suggested role in the evolution of language and speech, says Konopka. Many control brain development or have been linked to cognition. Others are involved in controlling body movement and guiding the development of facial and laryngeal tissues that are essential for articulation.

Evolutionary studies of Foxp2 suggest it acquired its human-specific changes in the last half million years of human evolution – roughly when language is thought to have emerged. Geschwind has done preliminary studies of the evolution of the 116 genes that Foxp2 affects, which suggest they may have a similar history. "It brings up the possibility, which is not at all remote, that these genes may have evolved in concert," he says, adding that this may even be true for other genes involved in language.

While the results hint at a central role for Foxp2 in the evolution of language, Geschwind cautions against calling it "the language gene" as some have in the past. "Either Foxp2 itself is pretty damn important," he says, "or it's part of a regulatory circuit – something else is regulating Foxp2 that no one else has found yet."

Geschwind's team carried out a second experiment, comparing patterns of gene activation in adult human and chimpanzee brain tissue. They found a striking overlap between the genes whose activity was different in the human brain tissue and the set of genes that are controlled differently by human Foxp2.

The finding is preliminary, but if confirmed, it might mean a significant part of the difference between human and chimpanzee brains could be explained by two small changes in one gene, says Wolfgang Enard. "That would be really amazing."

With 116 genes to follow up on, Geschwind and Konopka have their work cut out for them, says Pasko Rakic, a neuroscientist at Yale University. "This paper provides a starting point for future molecular studies on the basis of the evolution of language."

Faraneh Vargha-Khadem, a neuroscientist at University College London, who studies patients with Foxp2-linked language disorders, says Geschwind's list makes sense. In addition to their speech problems, her patients' lower faces are partly misshaped as well.

However, Vargha-Khadem cautions against distilling the evolution and development of language down to a single gene and its multitude of effects. Foxp2 may have helped endow humans with the machinery to produce speech, but this does not explain how abstract ideas get translated into utterances, she says.

"Almost by magic these muscles move to produce the sound sequence that makes sense to the listener," Vargha-Khadem says, adding that science has a long journey ahead to understand how the machinery works, let alone how it expresses our thoughts.

Journal reference: Nature, DOI: 10.1038/nature08549 (in press)

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