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Researchers at Broad Analyze Monkey DNA

By Carey Goldberg

What sets us apart from apes? At latest count, about four percent of our DNA.

Scientists announced Wednesday that they had completed analysis of the genome of a chimpanzee, humanity’s closest genetic relative, and found that the gap between humans and chimps is about 10 times smaller than the one between rats and mice.

“The philosophical goal is that we all want to know what makes us human,” said researcher Tarjei S. Mikkelsen of the Broad Institute of MIT and Harvard, which helped sequence the chimp genome. “The pragmatic goal is that it will help us understand diseases and conditions that are unique to humans.”

The analysis of the chimpanzee genome, performed by an international consortium and published Thursday in a series of papers in the journals Science and Nature, pinpoints genetic differences that have developed since chimpanzees and humans diverged from their common ancestor about six million years ago — differences that could prove useful in medical research.

For example, mutations in certain genes may help explain why chimpanzees are immune to some viruses that afflict humans. Another mutation makes chimps vulnerable to a blood parasite that cannot infect humans. A human mutation turned up in a gene connected to Alzheimer’s disease, important data for researchers working to seek a cure.

The chimp sequence also confirms several important predictions of evolutionary theory, researchers say. For example, regions of the genome that diverged the most between chimps and humans are the same ones that tend to be most different from human to human today, showing that the same evolutionary process is at work today.

“I can’t imagine Darwin hoping for stronger confirmation of his ideas than what we see when we compare the human and the chimp genome,” said Robert H. Waterston, whose University of Washington team also worked on the project.

Of the 40 million DNA differences found between humans and chimps, less than three million were in areas believed to be functionally important — meaning that a relatively small number of genetic differences account for the great divide between humans and apes.

But for anyone hoping that the chimp genome would reveal which genes contribute to defining traits of humanity — like standing on two legs or using complex language — more patience will be needed.

Researchers emphasized that, like the human genome, whose sequence has been known for four years, the chimp genome is only a starting point, a catalogue that will take years to mine.

For those who seek what makes humans unique, the latest genetic data offer “a long list, but it’s a much shorter list than it used to be,” said Eric Lander, director of the Broad Institute. “It’s not a very satisfying answer, but it’s the start of answering the question in a serious way.”

The chimp data turned up some good news for the Y chromosome, the set of genes that makes males male. Some scientists had argued in recent years that mutations have been causing the human Y to deteriorate to the point that it might even disappear in the far-distant future, depriving the world of men.

But work led by David Page, interim director of the Whitehead Institute in Cambridge, found that the human Y has been holding up better than the chimp Y. Contrary to descriptions of the human Y as a spacecraft out of control and soon to crash, Page said, the human-chimp comparison indicates that it is more like “a rocket that looks to be leveling out and has now re-established a very low orbit.”

The human genome differs most strikingly from the chimps’ in that a class of genes called transcription factors — genes that control other genes and can have dramatic effects on how an organism grows and develops — is changing much faster than in chimps.

It could be that the relatively fast changes in the transcription factors explain how human anatomy came to differ so strikingly from a chimp’s, said Mikkelsen, lead author of the main paper on the chimp genome published in Nature.

In any case, said Francis S. Collins, director of the National Human Genome Research Institute, “The real question about what it takes to be human, what makes us different, is more than a biological question.”