NATURAL selection may have changed almost one in ten of our genes since we split from other apes. Genes affected include ones connected to speech and hearing, and others involved in the development of the brain and skeleton. While it is too early to say whether these changes are the defining attributes that made us human, the researchers who made the discovery say it shows how fast our ancestors have evolved over the past 5 million years.
The results come from a comparison of over 7600 genes in humans and chimpanzees, the first study of its kind to compare so many genes in such closely related species. Because the analysis only looked at genes, which make up only about 3 per cent of the genome, it could be done before the sequencing of the whole chimpanzee genome, which was only completed earlier this month. The first analyses of the complete chimp genome are not expected until early 2004.
Michele Cargill at Celera Diagnostics in Alameda, California, and her team were examining the differences between the genomes of 39 humans when they realised that adding just one more individual, a chimpanzee, to their analysis would enable them to measure how much human genes have changed since our last common ancestor.
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Together with Andrew Clark and his colleagues at Cornell University in Ithaca, New York, Cargill’s team compared human and chimp sequences of each gene. By matching them to comparable sequences in the mouse, they identified mutations that were unique to the human lineage and then counted how many of these led to changes in the proteins produced by the genes, versus “silent” mutations that left proteins unchanged. If a gene shows more protein changes than expected, geneticists infer that evolution has been favouring changes in the gene.
And that’s what they found for 8.7 per cent of human genes. Of the 7645 genes for which the researchers had good data, 667 showed statistically significant evidence of evolution at work in the human lineage (Science, vol 302, p 1960). This is consistent with earlier work by Chung-I Wu and his team at the University of Chicago, which found that as many as a third of human genes have been modified by selection within the primate lineage in the past 30 million years. However, it calls into question the prevailing view that most differences between humans and chimps will be in the switches that turn genes on and off, rather than in the genes themselves.
“I think it’s a fantastic data set,” says Adam Eyre-Walker, an evolutionary geneticist at the University of Sussex, UK. “They’ve asked the right question, and we’ve potentially got a very interesting answer.” But he cautions that the genomes of chimpanzees and humans are so similar – they differ by only 1.2 per cent of their DNA bases – that each gene may bear too few mutations to draw trustworthy conclusions about what changes make us human.
Still, Cargill has pinpointed some intriguing genes that show signs of recent evolution – including several involved in the development of the skeleton and the brain, two structures that have clearly changed markedly since our lineage split from that of the chimp. Others of note include FOXP2, a gene involved in coordinating the movements of muscles in the face needed for speech, and alpha tectorin, which produces a protein used in the inner ear. People with a mutation in alpha tectorin have difficulty hearing high frequencies, which suggests that this gene might be important in speech perception. “It’s a little circumstantial, but the idea is that in order to understand speech we might have had to have changes in how the ear is made,” says Cargill.
Scientists have much more work to do to prove that these – or any other particular genes – have played a major part in the evolution of humans. But at the very least, Cargill’s results will help focus the search. “Rather than doing all of them, you could say I’m only going to look at the genes that are under selection in humans,” she says.