Humans and their close Neanderthal relatives began diverging from a common ancestor about 700,000 years ago, and the two groups split permanently some 300,000 years later, according to two of the most detailed analyses of Neanderthal DNA to date.
Using different techniques, two teams of scientists separately sequenced large chunks of DNA extracted from the femur of a 38,000-year-old Neanderthal specimen found in a cave 26 years ago in Croatia.
One team sequenced more than one million base pairs, and the other 65,000 pairs, of the genome.
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The achievements could help shed light on the evolution of our own species, and it paves the way for building a complete library of the Neanderthal genome, the scientists say.
No evidence of interbreeding
In popular imagination, Neanderthals are often portrayed as prehistoric brutes who became outsmarted by a more advanced species, humans, emerging from Africa.
But excavations and anatomical studies have shown Neanderthals used tools, wore jewelry, buried their dead, cared for their sick and possibly sang or even spoke in much the same way that we do.
Even more humbling, perhaps, their brains were slightly larger than ours.
The results from the new studies confirm the Neanderthals' humanity, and show that their genomes and ours are more than 99.5 percent identical, differing by only about 3 million bases.
"This is a drop in the bucket, if you consider that the human genome is 3 billion bases," said Edward Rubin of Lawrence Berkeley National Laboratory, who led one of the research teams.
By comparison, the genomes of chimpanzees, our closest living relatives, differ from humans by about 30 million to 50 million base pairs.
The findings also appear to refute speculation by some scientists that Neanderthals and humans interbred in more recent times.
"We see no evidence of mixing 30,000 to 40,000 years ago in Europe," Rubin said. "We don't exclude it, but from the data that we have, we have no evidence that pages were ripped from one genome and put in the other."
Ruling out contamination
One of the biggest challenges in sequencing Neanderthal DNA is finding a bone sample that hasn't been too contaminated by human handling.
Fortunately, the femur fragment used in the studies was relatively small and uninteresting, causing it to be largely overlooked.
The femur "was thrown in a big box of uninformative bones and not handled very much," said Svante Paabo of the Max Planck Institute for Evolutionary Anthropology in Germany, leader of the other sequencing project. "Whereas more interesting bones — where you can study the muscle attachment and the morphology of Neanderthals — had been extensively cleaned and handled and thus tend to be much more contaminated."
The researchers also relied on other clues, such as chemical damage unique to ancient DNA, to help verify that the genetic material was indeed Neanderthal.
"One of the crucial things is that we feel confident that the DNA we have, which we're calling Neanderthal, is truly Neanderthal," Rubin said.
The success of the two team's sequencing projects were made possible by recent advances in DNA sequencing technology, which now allow scientists to sequence DNA over 100 times faster than in the past.
Paabo's team recovered more than a million Neanderthal base pairs using a new automated technique called pyrosequencing.
In this process, DNA fragments are attached to tiny artificial beads, sequenced and then matched to similar sections on human chromosomes.
Rubin's team employed "metagenomics," which involves integrating short fragments of extracted Neanderthal DNA into the genomes of bacteria.
The Neanderthal DNA gets amplified as the bacteria divide, and then scientists pluck out human-matching bases using "probes" made with snippets of human DNA.
The researchers say their achievements mark the "dawn of Neanderthal genomics," and they estimate that further advances in DNA sequencing technology could allow the completion of a very rough draft of the entire Neanderthal genome within two years.
"There's no question that we're going to have a Neanderthal genome, and likely, we're going to have several Neanderthal genomes," Rubin said.
The team hopes to extract and sequence DNA from the bones of other individuals and to complete several drafts of the Neanderthal genome.
Clues to our past
A complete Neanderthal genome would help scientists identify the genetic changes in our own genome that set us apart from other hominids.
The comparison between recently sequenced chimpanzee genomes and ours is already shedding light on the evolutionary changes our ancestors went through to make them less ape-like.
But because chimps and humans began diverging some 6.5 million years ago, examination of the chimp genome cannot reveal what happened in the more recent stretches of our own evolution.
"Humans went through several stages of evolution in the last 400,000 years," said study co-author Jonathan Pritchard of the University of Chicago. "If we can compare humans' and Neanderthals' genomes, then we can possibly identify what the key genetic changes were during that final stage of human evolution."
A completed genome will also reveal new insights about Neanderthals, who disappeared mysteriously about 30,000 years ago.
"In having the Neanderthal genome sequence ...we're going to learn about the biology, learn about things that we could never learn from the bones and the artifacts that we have," Rubin said.
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