BioEd Online

Geneticists have finished reading one of the most important volumes in the library of life: the DNA of the chimpanzee. Decoding the sequence of our comrade in apehood may help to answer the age-old question of what makes us human.

The US-led Chimpanzee Sequencing and Analysis Consortium, which presents the sequence in this week's Nature¹, has already begun making such comparisons. By lining the Pan troglodytes sequence up against the human genome, it has spotted six areas of our own DNA that have been rigorously sculpted by natural selection. The areas include one that contains a gene known to be crucial for that most human of traits, speech.

"We have targeted regions of genes that look like they'll be really important for investigating the differences between chimps and humans," says consortium member Evan Eichler of the University of Washington School of Medicine in Seattle.

In the lists

The chimpanzee joins an extensive roster of species that have been given the genome-sequencing treatment. The list now numbers in the hundreds, including a host of bacterial species and pathogens, the mouse, rice, and family favourites such as the dog.

Waiting in the wings are a diverse bunch including guinea pigs, domestic cats and a motley crew of parasites and moulds (see ' Decoders target 18 new genomes').

The chimpanzee consortium assembled its sequence using the now de rigeur method of whole-genome shotgun sequencing. This involves cutting up the entire sequence, some 3 billion letters of code in the chimp's case as in the human genome, sequencing each section, and reassembling the jigsaw by computer.

The process has got cheaper and easier since the human genome was unveiled in 2001, after more than a decade of struggle costing hundreds of millions of dollars. The chimp genome cost no more than an estimated US$50 million.

Some 98% of the data came from blood samples from a single common chimpanzee, called Clint, who lived at the Yerkes National Primate Research Center in Atlanta, Georgia. Clint died after a heart failure in January this year at the tender age of 24; most chimps live into their 50s.

Home truths

So what does Clint's DNA actually tell us? For a start, humans and chimps are not quite the close cousins we thought. Crude past comparisons of our DNA showed that our sequences were between 98.5% and 99% identical. That is indeed the case when considering single-letter differences in the DNA code, of which there are 35 million, adding up to about 1.2% of the total sequence.

But there are other differences, Eichler says. The two sequences are littered with duplicated segments that are scattered in different ways in the two species, he reports in a separate analysis². These regions add another 2.7% of difference to the tally. "So the 1.2% figure is woefully inaccurate," says Eichler.

Much of the difference is seen in genes involved in the immune system. The contrast suggests that humans and chimps came up against different diseases during our evolutionary upbringing, Eichler explains.

The most fertile grounds for human gene duplications are regions near the ends of chromosomes called subtelomeres, reports a team led by Barbara Trask of the Fred Hutchinson Cancer Research Center in Seattle³. These areas are still poorly understood, she says, and could tell us more about our own evolution.

But in terms of what makes us human, the most exciting areas of our genome are six regions, containing a few hundred genes, that show very little variation from human to human, but more variation in chimps. This implies they were important in our evolution. Enticingly, says Eichler, one of these regions is home to a gene called FOXP2, which is crucial for producing coherent speech.

Could this be the thing that really sets us apart from other apes? Eichler warns against getting too excited just yet. "I'm a bit pessimistic that this is the silver bullet," he says. "But it's a part of it."