Using remarkably well-preserved DNA extracted from a fossil thighbone, researchers have sequenced the genome of a 45,000-year-old anatomically modern human -- the oldest complete Homo sapiens genome on record. The work, published in Nature this week, revealed fragments of Neanderthal DNA and helps pinpoint when they interbred with our direct ancestors.

In 2008, a relatively complete left femur from an adult male was discovered on the banks of the river Irtysh (pictured below) near the settlement of Ust’-Ishim in western Siberia. A large international team led by Harvard and Max Planck researchers retrieved, sequenced, and analyzed his genome, which represent the oldest directly radiocarbon-dated modern human outside Africa and the Middle East. His diet consisted mostly of plants or plant-eating fish, and his genetic code suggests that he has no living descendants today.

The Ust’-Ishim man is more related to people living outside Africa today than to Africans -- making him a member of one of the most ancient non-African populations. They also compared him to other ancient skeletons -- a 24,000-year-old boy from Mal’ta in Siberia and an 8,000-year-old man from La Braña, Spain, Science reports -- and found that he’s equally related to both. That means he lived just before or around the time human populations in western and eastern Eurasia split from each other.

“The ancient Siberian was related equally to West European hunter-gatherers, North Asian hunter-gatherers, East Asians, and the indigenous people of the Andaman Islands off South Asia,” Harvard’s Qiaomei Fu tells the Harvard Gazette. Among present-day populations, however, he’s more closely related to East Asians than to Europeans -- suggesting that Europeans today inherited some of their genes from a different, unknown source, likely a population that left Africa in a later wave.

Neanderthals were still present in Eurasia while he was alive, and sure enough, he carried a similar level of Neanderthal ancestry as present-day Europeans and Asians: 2.3 percent of his genome. Just about everyone living outside of Africa today carry between 1.7 and 2.1 percent Neanderthal DNA. But because the segments in the Ust’-Ishim man are much longer, Neanderthal gene flow into his ancestors must have occurred 7,000 to 13,000 years before his time. That means his ancestors mixed with Neanderthals “about 50,000 to 60,000 years ago, which is close to the time of the major expansion of modern humans out of Africa and the Middle East,” Janet Kelso of the Max Planck Institute for Evolutionary Anthropology says in a news release.

Previous estimates of the timing of interbreeding between modern humans and Neanderthals ranged wildly from 37,000 and 86,000 years ago. "This new paper definitively says it was modern humans with modern human behavior that interbred with Neanderthals," Harvard’s David Reich tells New Scientist.

Furthermore, by measuring the number of mutations missing in this individual and comparing them with people now, the team found that between one and two mutations per year have accumulated in the genomes of European and Asian populations since the Ust’-Ishim man lived. This slow mutation rate might push back the human-Neanderthal split by hundreds of thousands of years.

Images: Bence Viola, MPI EVA