By LINDA SEEBACH
Scripps Howard News Service
August 26, 2005
People who have a defective copy of the gene experience a wide variety of language difficulties. Some of them are physical, related to inability to control the lower part of the face well enough to produce intelligible speech. But others are purely linguistic, involving vocabulary and grammar.
On his Web site evolutionpages.com, Alec MacAndrew tells the story of the hunt for FOXP2. Around 1990, scientists began studying a three-generation family in London, identified in the literature as "KE," about half of whose members had the same severe speech difficulties. The pattern of inheritance strongly suggested that the condition was the result of a mutation in a single gene, but left unanswered the question of what the gene did that could cause such a variety of effects.
A paper published in 1995 (full citations in MacAndrew's article) identified "defects in processing words according to grammatical rules; understanding of more complex sentence structure such as sentences with embedded relative clauses; inability to form intelligible speech; defects in the ability to move the mouth and face not associated with speaking (relative immobility of the lower face and mouth, particularly the upper lip); and significantly reduced IQ in the affected compared with the unaffected in both the verbal and the non-verbal domain."
In 1998, Simon Fisher and colleagues identified a short stretch of DNA on chromosome 7 as the likely location of the gene, and in 2001 C.S.L. Lai and others found the exact mutation, which changes a single letter in the genetic code, which changes a single amino acid in a protein the gene codes for. The gene is one of a class called forkhead binding domains, or FOX for short. It is so named because fruit flies with a mutated version of the gene have bizarrely spiked heads, according to a paper on FOXP2 from the Wellcome Trust.
"The particular amino acid that is mutated in the unfortunate members of the KE family is extremely highly conserved," MacAndrew writes. "In all cases where FOX genes have been sequenced, from yeast to people, that amino acid is always an arginine: always, every time, except in affected members of the KE family where the residue is a histidine."
In the 75 million years since the evolutionary line that led to mice separated from the line that led to primates (and eventually to us), only one amino acid of the protein FOXP2 codes for differs between rhesus monkeys, gorillas and chimpanzees, which are identical, and mice. There have been two changes in the human lineage since it split with the chimpanzee line about 6 million years ago.
Yeast? Fruit flies? Mice? Whatever this thing is doing, it can't be primarily "a language gene," as it was widely hailed in the press at the time. (To MacAndrew's proper scorn, it should be noted.) The real story, he says, is what kind of gene it is; namely, one that produces a protein that turns other genes on or off.
"The key point, that all the popular reports missed, is that FOXP2 is a transcription factor - in other words it has the potential to affect the expression of an unknown, but potentially large number of other genes. No wonder the syndrome presents in such a diffuse way."
He predicted that if researchers "broke" the gene in mice, where is it known to be important in the embryonic development of the brain, they would see abnormalities in brain function and structure.
And that's what happened. MacAndrew added a link to a paper published in June, by Weiguo Shu and others, which concluded: "Disruption of both copies of the FOXP2 gene caused severe motor impairment, premature death, and an absence of ultrasonic vocalizations that are elicited when pups are removed from their mothers. Disruption of a single copy of the gene led to modest developmental delay but a significant alteration in ultrasonic vocalization in response to such separation."
The researchers said the gene likely "plays an instrumental role in the developmental process that subsumes social communication functions in diverse organisms."
Not language exactly, therefore, but not entirely unrelated to it, either.
The changes in the human amino acid are believed to be relatively recent, from 100,000 years ago to 10,000, and of a kind that might well have been functionally significant in the development of human language. But they're obviously not the entire story. Anatomy counts, too. "The larynx has descended so that it provides a resonant column for speech (but, as an unfortunate side-effect, predisposes humans to choking on food)," MacAndrew says. "Also, the nasal cavity can be closed thus preventing vowels from being nasalised and thus increasing their comprehensibility." Those changes, he believes, could not have happened in as short a time as 100,000 years.
Tracing the evolution of language is a huge challenge; we're not going to find fossils. But we may find the evidence written in our own cells.