Modern humans most likely interbred with Neanderthals, according to landmark genome analysis that shed light on how we evolved differently from our prehistoric cousins.
Experts are now convinced that early modern humans and Neanderthals interbred between 50,000 and 100,000 years ago.
Inter-human relations occurred as the first pioneering bands of Homo sapiens ventured out of Africa, scientists believe.
When they reached the Middle East they ran into groups of Neanderthals who preceded them.
The rest, as they say, is history.
As a result, between 1 per cent and 4per cent of the DNA of non-African people alive today is Neanderthal, according to the research.
The discovery emerged from the first attempt to map the complete Neanderthal genetic code, or genome.
It more or less settles a long-standing academic debate over interbreeding between separate branches of the human family tree.
Evidence in the past has pointed both ways, for and against modern humans and Neanderthals mixing their genes.
Technically the Neanderthals, Homo neanderthalensis, were a human sub-species which parted evolutionary company from our direct ancestors between 270,000 and 440,000 years ago.
Around 400,000 years ago early Neanderthals stepped out of their African cradle, where Homo sapiens was still evolving, and headed for Europe and Asia. At least 300,000 years later early modern humans followed the Neanderthals out of Africa.
The two populations co-existed in Europe and Asia until the Neanderthals vanished forever around 30,000 years ago – probably driven into extinction by the smarter and more competitive modern humans.
Previous genetic evidence has cast doubt on the likelihood of Homo sapiens and Neanderthals interbreeding.
But this was based on analysis of a limited form of DNA locked in the mitochondria, bean-shaped energy-generating bodies in cells.
The new genome sequence published today in the journal Science covers around 60 per cent of the whole Neanderthal genetic code, as imprinted in the chromosomes of cell nuclei.
To highlight any differences, scientists compared the Neanderthal genome to those of present-day humans from southern and west Africa, China, Papua New Guinea and France.
They were surprised to find that Neanderthals were more closely related to modern humans from outside Africa than to Africans.
Even more mysteriously, the relationship extended to people from eastern Asia and the western Pacific – even though no Neanderthal remains have been found outside Europe and western Asia.
The most likely explanation is that Neanderthals and Homo sapiens interbred before early modern humans struck out east, taking traces of Neanderthal with them in their genes.
Professor Svante Paabo, director of evolutionary genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, who led the international project, said: “Since we see this pattern in all people outside Africa, not just the region where Neanderthals existed, we speculate that this happened in some population of modern humans that then became the ancestors of all present-day non-Africans.
“The most plausible region is in the Middle East, where the first modern humans appeared before 100,000 years ago and where there were Neanderthals until at least 60,000 years ago.
“Modern humans that came out of Africa to colonise the rest of the world had to pass through that region.”
He added: “Those of us who live outside Africa carry a little Neanderthal DNA in us.”
The scientists calculated that Neanderthal DNA makes up between 1 per cent and 4 per cent of modern non-African genomes.
Such a faint genetic signature suggests only a small amount of interbreeding. When the first modern humans left Africa they did so in groups numbering just tens to hundreds of individuals.
But even a few instances of interbreeding among such a small population would have had a global impact as their numbers expanded.
Co-author Dr Richard Green, from the University of California at Santa Cruz, said: “How these peoples would have interacted culturally is not something we can speculate on in any meaningful way.
But knowing there was gene flow is important and it is fascinating to think about how that may have happened.”
The research, which took four years, involved disentangling and making sense of 1.1 billion DNA fragments taken from Neanderthal bones.
Over time the DNA had degraded into small pieces and much of it was chemically modified.
Most of the 400 milligrams of bone powder used came from three female bones recovered from Vindija cave in Croatia and dated to around 40,000 years old.
Other samples were from Russia, Spain and Germany. New cutting-edge techniques were used to avoid confusion with DNA from contaminating microbes and human contact.
The analysis highlighted certain parts of the Neanderthal genome which resembled those of chimpanzees more than modern humans.
Several genes were discovered that differed between Neanderthals and Homo sapiens and may have played important roles in the evolution of modern humans.
They included genes involved in mental functions, metabolism, and development of the skull, collar bone and rib cage.