What happened to the Neanderthals? Check their DNA.

Humans' closest cousins, the Neanderthals, vanished 30,000 years ago after sharing turf with humans for millenniums. But why they disappeared remains a mystery.

Two research teams decided to try a new approach: Instead of studying tiny fragments of DNA from one of these cousins, they looked for ways to string fragments together to get a more complete source of potential genetic clues. Conventional wisdom held that this task was impossible for material this old. But using the 38,000-year-old remains of a 38-year-old male, found in a Croatian cave, each group now says it has rebuilt, or sequenced, long segments of Neanderthal DNA – the twisted, ladder-shaped molecule in the nucleus of cells that holds an organism's genetic blueprint.

The technique is not only yielding new insights into Neanderthals, reported in Thursday's issue of the journal Nature and Friday's issue of Science, it's also likely to prove an important tool in teasing out secrets about how plants and animals evolved, researchers say. DNA "is the ultimate forensic record of evolution," says Sean Carroll, an evolutionary biologist at the University of Wisconsin-Madison. "There's never been a more exciting time to be an evolutionary biologist."

Within the next two years, one team hopes to finish a rough draft of the Neanderthal's full genome. This would help scientists answer nagging questions about the Neanderthals' evolutionary history, including factors contributing to their demise. It also would yield insights into the evolutionary history of modern humans.

"We are at the dawn of Neanderthal genomics," says Dr. Rubin, with the US Department of Energy's Joint Genome Institute in Walnut Creek, Calif. He likens the effort to those of archaeologists who deciphered hieroglyphics to learn about ancient Egyptians in detail.

The results that will be published this week are "really a big teaser," says Anne Stone, who heads the Molecular Anthropology Laboratory at Arizona State University. But it's an important one, she adds. The sequences the two teams have produced cover 65,000 to 1 million base pairs. Each base pair is built from four basic chemicals that make up an organism's genetic "code." Each base pair forms a "rung" on the DNA molecule's ladder. By comparison, the human genome, and presumably the Neanderthal's, consists of some 3 billion base pairs. But the DNA strands that the teams have strung together are far longer than any previous length of Neanderthal DNA.

The samples are based on DNA in the cell nucleus. This DNA carries contributions from a father and a mother. Earlier DNA sequences involved so-called mitochondrial DNA, which an offspring inherits from its mother. Thus, the sequences the two teams are building represent a fuller biological picture of Neanderthals than previous efforts would paint.

Although the genome is far from complete, the teams have used the data to test questions about the history of humans and Neanderthals. One centers on the contentious issue of whether the two species interbred during the 10,000 to 20,000 years they shared the same territory in Europe and western Asia. Several paleo-anthropologists hold that the fossil record points to some interbreeding.

Dr. Rubin's group says that the genetic information his group has gathered so far shows no signs of interbreeding. The second team, led by Dr. Paabo of the Max Planck institute for Evolutionary Anthropology in Leipzig, Germany, suggests genes may have been mixed, but only in one direction – from male humans to Neanderthal females. Both groups, however, note that the data are still too sparse to be conclusive.

Both teams estimate that anatomically modern humans and Neanderthals trace their roots to a common population of hominids some 500,000 to 700,000 years ago. The ultimate split came between 370,000 and 516,000 years ago. These rough estimates dovetail with the fossil record, notes Erik Trinkaus, a physical anthropologist at Washington University in St. Louis.

Still, Dr. Trinkaus says he sees problems with how the two teams interpret some of their information. On the question of interbreeding, he continues, the teams need to compare genes from Neanderthals with those from early modern humans, not the 21st-century humans for which genetic information exists.

The full genome of an individual Neanderthals would go a long way, Dr. Stone adds. It would enable researchers to answer a range of questions about human and Neanderthal evolution as scientists compare genes from the two hominid groups, as well as from chimpanzees (the closest living relative to Homo sapiens)

The two teams are trying to address the sampling issue by developing more ways to glean more information from smaller samples. And Rubin's team has established a living library of Neanderthal DNA – cloning segments, then cataloging it and storing it in bacteria. Thus, the teams expect to have enough raw material from their sample to make several copies of the genome, turning it from a sketch into a finished blueprint for Neanderthal biology.

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