Scientists Reconstruct Neanderthal Gene Code

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WASHINGTON — Scientists said yesterday that by unleashing a new kind of DNA analyzer on a 38,000-year-old fragment of fossilized Neanderthal bone that they had reconstructed a portion of that creature’s genetic code — a technological tour de force that has researchers convinced they will soon know the entire DNA sequence of the closest cousin humans ever had.

Such a feat, unanticipated even a few years ago, could tell a lot about what Neanderthals were like, from their hair and skin color to their relative facility with language. It could also clear up what sort of relationship existed between them and the first modern humans — including whether the two tribes continued to interbreed after they diverged onto separate evolutionary trajectories.

Perhaps most tantalizing, the newfound capacity to reconstruct prehistoric DNA should allow scientists to home in on the less than one-half of 1% of the human genome that is expected to be different from that of Neanderthals, who went extinct 30,000 years ago.

Those differences, scientists said, essentially spell out in biological terms what makes humans human.

The new findings, by research teams in Germany and California, “are perhaps the most significant contributions published in this field since the discovery of Neanderthals 150 years ago,” David Lambert and Craig Millar wrote in a commentary in the journal Nature, which along with the journal Science is publishing the work this week. Messrs. Lambert and Millar, who were not involved in the work, are both specialists in molecular evolution at universities in New Zealand.

“Personally, I was blown away when I first heard wind of this,” a Howard Hughes Medical Institute investigator and evolutionary geneticist at the University of Wisconsin at Madison, Sean Carroll, said.

As the most closely related and recently departed members of the human family tree — and as the widely recognized, boney browed icons of stonier times — Neanderthals have long fascinated scientists and armchair paleo-anthropologists alike. They and their counterparts — our human forebears — started as equals hundreds of thousands of years back, but took very different paths.

One line went on to develop all that human culture is today, from haute couture to DNA synthesizers. The other, while not as primitive as often described, mysteriously disappeared in a wave of die-outs that started in Western Asia about 45,000 years ago and ended with their extinction in Europe about 15,000 years later.

Some say climate change did them in. Some blame the modern humans who were expanding throughout Europe at the time and who, thanks apparently to some fortuitous genetic mutations, were enjoying an intellectual and socio-cultural awakening.

The quest to understand Neanderthals on the level of molecular genetics was for a long time seen as hopeless. DNA, which holds the instructions for life that are contained in virtually every living cell, breaks down with time.

A few researchers — most notably Svante Paabo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany — have managed to extract DNA fragments from 5,000-year-old Egyptian mummies, and even stitch a few together in proper sequence. But the DNA pieces from much older specimens are so small that no technology could put them all together again with any semblance of accuracy.

Complicating matters further, prehistoric bones are heavily contaminated with the DNA from bacteria, as well as with modern human DNA from the scientists who discovered and handled them. That is one reason why no extinct animal has ever had its genome fully sequenced.

But the technology for detecting, analyzing, and reconstructing disintegrated DNA has evolved at a stunning rate. As part of an ongoing, ambitious effort to catalogue every life form on Earth, companies have developed machines that can tell whether a snippet of DNA came from the same organism as another snippet — and if so, whether the two DNA fragments were once attached to one another. Stitch by stitch, an organism’s genome, or complete genetic code, can quickly come into view.

To do so with Neanderthal DNA, Mr. Paabo and his colleagues first tested more than 70 Neanderthal tooth and bone samples to see which had the smallest proportion of contaminating DNA. (Some 300 partial skeletal remains are known worldwide, their preservation and discovery aided by the Neanderthals’ tradition of burying their dead.)


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