Early humans not only lived side-by- side with Neanderthal cave-dwellers, they probably mated with them, an analysis of ancient DNA showed.
As a result of these interspecies liaisons, as much as 4 percent of the genes of modern people living outside of Africa originated with Neanderthals, according to a report on the mapping of the Neanderthal genome published Thursday in the journal Science.
An international research team used dental drills to tease powder and DNA from the 40,000-year-old bones of three females found in a Croatian cave and then sequenced the DNA. By comparing these ancient genes to those of modern people, the scientists say they've settled the debate over human-Neanderthal sex and are filling in pieces of our evolutionary history.
"We're able to largely resolve the controversy," said study co-author David Reich, an associate professor of genetics at Harvard Medical School in Boston. "The main finding is that there was gene flow from Neanderthals into the genomes of all modern non-Africans."
The researchers, led by Svante Paabo of the Max Planck Institute for Evolutionary Biology in Leipzig, Germany, compared the genome of the Neanderthals to those of five modern humans from Africa, Papua New Guinea, China and France. They found that 1 percent to 4 percent of the genes of the Asians and Europeans came from Neanderthals, while the Africans had no genes that were uniquely Neanderthal in origin.
This suggests that Neanderthal genes made their way into the population of early humans shortly after some humans had left Africa and before they had migrated much further, Reich said in a telephone briefing with reporters Wednesday.
"The most simple explanation for where that might have occurred is somewhere in the Middle East or northern Africa at the gateway of Africa as modern humans were migrating out for the first time" at least 45,000 years ago, Reich said.
The genome sequence the team stitched together is about 60 percent complete, Reich said, enough to provide a representative look at the genetic makeup of the Neanderthals, who became extinct 30,000 years ago. Fossils with features typical of Neanderthals date to about 400,000 years ago and have been found in Europe and central Asia from Siberia to the Middle East.
The Neanderthals were stocky and muscular with short arms and legs and a large head, jutting brow and brain slightly larger than ours.
The scientists hunted for stretches of genes where variations frequently pop up in the human genome and not in the Neanderthal. That's a way to identify genetic changes that may have provided a survival advantage to humans, said Ed Green, a genome biologist at the University of California, Santa Cruz, and one of the study's authors.
"This is a very powerful method for shining light" and for "finding those important changes that happened at a really crucial time in human evolutionary history," Green said.
The scientists identified 212 regions with these types of variations including 20 where the evidence was strongest. Among them are three genes that, when mutated, affect cognitive development and have been linked to autism, schizophrenia and Down syndrome, the team reported.
"I really thought until six to seven years ago that it would remain impossible in my lifetime to sequence the entire Neanderthal genome," Paabo said.
That changed with the development of new high-speed gene- sequencing technology in the past several years, and of new techniques for extracting ancient DNA and separating it from the genetic material deposited over the centuries by animals and microbes. About 96 percent of the DNA they extracted from the bones was not from the Neanderthals themselves, Green said.
"It's not an easy thing to get a genome sequenced out of bones that are 40,000 years old," Green said in a May 4 telephone interview. "There's bacterial DNA and fungal DNA and they don't come with labels."
The team took advantage of huge libraries of DNA sequences that have been created from animal and microbial species to search for sections that could be recognized as non-Neanderthal and eliminated, Green said.
The researchers are just beginning the hunt for areas of the genome where there is evidence of significant change in a short period of time. Such rapid genetic change is a sign of evolution since mutations that provide a survival advantage tend to live on and be found in the genes of subsequent generations.
"The Neanderthals are not totally extinct," Paabo said. "Some of them live on in us."