New Methods Let Scientists Analyze Neanderthal DNA

Complicating matters, prehistoric bones are heavily contaminated with DNA from bacteria and from scientists who have handled them. That is one reason no extinct animal has ever had its genome fully sequenced.

But the technology for detecting and reconstructing disintegrated DNA has evolved at a stunning pace. Machines can now tell whether a snippet of DNA came from the same organism as another snippet -- and if so, whether the two fragments were once attached. Bit by bit, an organism's genome, or full genetic code, can come into view.

To do so with Neanderthal DNA, Paabo's team focused on a bone discovered decades ago in a Croatian cave. Though more than 90 percent of the DNA was from bacteria, virtually all of the rest appeared to be Neanderthal, recognizable by its similarity to human DNA but with stretches resembling chimpanzee.

The bone had stayed clean, Paabo said, because "it's rather small and uninteresting and was thrown in a big box of 'uninformative' bones and was not handled much by people."

Paabo's team then turned to 454 Life Sciences of Branford, Conn., which is developing high-speed DNA analyzers with the goal of being able to offer affordable, personalized, full-genome analyses.

In a test run on 20 grams of pulverized bone, the machine placed in order 1 million letters -- or "bases" -- of Neanderthal genetic code, Paabo and his colleagues report in today's Nature.

That is less than one-thousandth of the entire anticipated genome. But a full cracking of the Neanderthal code should be complete in about 18 months, Paabo said.

"Clearly, we are at the dawn of Neanderthal genomics," said Edward M. Rubin of the Department of Energy's Joint Genome Institute in Walnut Creek, Calif., and the Lawrence Berkeley National Laboratory. Rubin led a second team that used a different method to sequence 65,250 bases from the same Neanderthal bone, landmark work complementary to Paabo's, described in tomorrow's issue of Science.

"We're going to be able to learn about their biology, learn things we could never learn from the bones or artifacts," Rubin said. "This data will serve as a DNA time machine."

Scientists have already identified a few lucky genetic glitches that may have helped launch humans to global dominance while our stocky cousins turned toward an evolutionary dead end. One, in a gene called FOXP2, may have facilitated language. Another may have driven a big increase in brain size.

Until now, the only Neanderthal DNA that scientists had looked at was a smidgeon of "mitochondrial" DNA, of limited value because it does not contain genes involved in appearance, intelligence or language.

The new reports confirm early suggestions that modern humans and Neanderthals split into two genetically distinct groups about 500,000 years ago. They also show no evidence of interbreeding, though a final answer to that question must await further analysis.

The most exciting thing about the new technology is its promise of allowing a first comparison of DNA from humans, Neanderthals and chimpanzees, our closest living relatives, said Chris Stringer of London's Natural History Museum.

"We should then be able to pin down unique changes in each genome," Stringer said, "to show how we came to be different from each other."