In The Field

ASHG 2009: If mice could speak

Everyone wants to find the genes that “make us human.” The problem is, when we find them, how will we know?

A talk last night by Raymond Clarke of the University of New South Wales in Australia posed this dilemma. Clarke and his colleagues, Zhi Fang of the University of New South Wales and Zhongming Zhao of Vanderbilt University in Nashville, Tennessee, believe they have found a new gene that could have been crucial to the development of human language. Unlike FOXP2, the most famous “language gene,” Clarke and his coworkers believe their gene regulates the development of the human larynx – the tissue in the human throat that allows us to speak. (FOXP2, in contrast, is involved in brain development).

Clarke and his colleagues have studied a family that has an inherited speech impairment caused by a malformed larynx; the worst affected members of the family can hardly speak above a whisper. Clarke’s group traced the root of the problem to a broken gene on chromosome 8. The gene, which Clarke’s group calls tospeak, is not transcribed into a protein. Rather, Clarke’s group claims, it contains a regulatory element called an “enhancer” that promotes the transcription of another gene, growth and differentiation factor 6 (GDF6), which, when mutated in mice, causes malformations in the larynx and joints that look similar to those seen in the family affected by the speech problem.

Clarke says tospeak is unique to primates – humans and their relatives, such as chimpanzees – and doesn’t exist in its exact current form in other mammals. That raises the question of how he can be sure that it does what he thinks it does. Usually, scientists can check this out by knocking out the gene in mice, and watching what happens. But if the gene doesn’t exist in mice, this isn’t possible. And since mice don’t speak like humans do, it’s not clear what good it would do to engineer mice containing the gene. Clarke was challenged on this point by the audience: how do you know that you’re not just seeing some other genetic perturbation that affects GDF6? How do you really know tospeak is involved? Clarke appeared apologetic: “I’m sorry; I can’t put it in a mouse,” he said.

This is not a dilemma unique to tospeak; any other gene responsible for “uniquely human” traits will be similarly difficult to study in other model organisms. There is another way to check them out, however; part of the rationale for sequencing the genome of another human species, the Neanderthal, was that it would help shed light on human evolution and uniquely human traits.

Clarke, in fact, said that he had asked the scientists studying the Neanderthal genome for any information they had about tospeak. “They declined,” Clarke said, “and said they would publish their data within the month.” That drew murmurs of disapproval from the audience.

It’s surely a coincidence that Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, is both a leader of the Neanderthal genome project, and has made his reputation with studies on what had previously been the only really famous language gene – FOXP2.


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