The DNA sequences of humans and chimpanzees are 98 percent identical. Yet that 2 percent difference represents at least 15 million changes in our genome since the time of our common ancestor roughly six million years ago. Now a new computational technique has identified 49 regions that have changed particularly quickly between humans and chimps, and may have revealed at least one gene critical to the development of our larger brains.

Katherine Pollard of the University of California, Davis, first used computers to search for segments of DNA that showed the most changes between human and chimp genomes. The computers identified 49 such areas in the human genome, dubbed human accelerated regions (HAR). The most radical revolutionary, tagged as HAR1, transformed 18 of its 118 nucleotides in the course of the last few million years; only two had changed in the prior 310 million years that separate chickens from apes. "It's really an extreme case," Pollard notes.

Closer observation of the region by Sofie Salama of the University of California, Santa Cruz, revealed that it overlaps with two neighboring genes: HAR1F and HAR1R. These genes do not code for proteins that then carry out a particular function in the body, rather they produce a messenger RNA (mRNA) molecule that guides the production of proteins by other genes.

Further experiments by an international team of collaborators revealed that HAR1F is strongly expressed in the developing neocortex of human embryos, starting in the seventh week. The mRNA is produced by Cajal-Retzius neurons, which previous research has shown to direct the creation of the layers of neurons in the human cortex. These cells also produce the protein reelin, which helps create the architecture of the human brain. The corresponding gene in other primates plays a similar role, according to experiments with crab-eating macaques.

Although this research does not definitively link this region to brain differences between humans and our closest relatives, it is intriguing. "We don't know what it does, and we don't know if it interacts with reelin, but the evidence is very suggestive that this gene is important in the development of the cerebral cortex, and that's exciting because the human cortex is three times as large as it was in our predecessors," notes team leader David Haussler of the University of California, Santa Cruz. "Something caused our brains to evolve to be much larger and have more function than the brains of other mammals."

And, of course, this is just the first of the 49 rapidly evolving regions to be studied. "Now we have to go through the other 48," Haussler says. Nature published the paper presenting the research online yesterday.