Reconstructed Genome of 45,000-Year-Old Man Offers Clues on Modern Humans

In 2012, Dr. Paabo and his colleagues took samples from this thigh bone to search for DNA. To their surprise, it held a number of genetic fragments.

Scientists have reconstructed the genome of a man who lived 45,000 years ago, by far the oldest genetic record ever obtained from modern humans. The research, published on Wednesday in the journal Nature, provided new clues to the expansion of modern humans from Africa about 60,000 years ago, when they moved into Europe and Asia.

And the genome, extracted from a fossil thighbone found in Siberia, added strong support to a provocative hypothesis: Early humans interbred with Neanderthals.

“It’s irreplaceable evidence of what once existed, that we can’t reconstruct from what people are now,” said John Hawks, a paleoanthropologist at the University of Wisconsin who was not involved in the study. “It speaks to us with information about a time that’s lost to us.”

The discoveries were made by a team of scientists led by Svante Paabo, a geneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Over the past three decades, Dr. Paabo and his colleagues have developed tools for plucking out fragments of DNA from fossils and reading their sequences.

Early on, the scientists were able only to retrieve tiny snippets of ancient genes. But gradually they have invented better methods for joining the overlapping fragments together, assembling larger pieces of ancient genomes that have helped shed light on the evolution of humans and their relatives.

In December, they published the entirety of a Neanderthal genome extracted from a single toe bone. Comparing Neanderthal to human genomes, Dr. Paabo and his colleagues found that we share a common ancestor, which they estimated lived about 600,000 years ago.

Recently, Dr. Paabo and his colleagues got an opportunity to test their new methods on an exceptional human bone.

In 2008, a fossil collector named Nikolai V. Peristov was traveling along the Irtysh River in Siberia, searching for mammoth tusks in the muddy banks. Near the settlement called Ust'-Ishim, he noticed a thighbone in the water. Mr. Peristov fished it out and brought it to scientists at the Russian Academy of Sciences.

The Russian researchers identified the bone as a modern human, not a Neanderthal. To determine its age, they sent samples to the University of Oxford. Scientists there measured the breakdown of radioactive carbon and determined the bone was about 45,000 years old — making it the oldest modern human fossil ever found outside of Africa and the Near East.

In 2012, Dr. Paabo and his colleagues took samples from the bone to search for DNA. To their surprise, it held a number of genetic fragments.

“This is an amazing and shocking and unique sample,” said David Reich, a geneticist at Harvard Medical School and co-author of the new study.

The researchers used the DNA fragments to recreate a high-resolution copy of the man’s complete genome. A Y chromosome revealed that the thighbone belonged to a man.

The scientists then compared the genome of the so-called Ust'-Ishim man to those of ancient and living people.

They found that his DNA was more like that of non-Africans than that of Africans. But the Ust'-Ishim man was no more closely related to ancient Europeans than he was to East Asians.

He was part of an earlier lineage, the scientists concluded — a group that eventually gave rise to all non-African humans.

Homo sapiens, our own species, appeared in Africa around 200,000 years ago. Previous studies — both on genes and fossils — have suggested that they then expanded through the Near East to the rest of the Old World.

The Ust'-Ishim man’s genome suggests he belonged to a group of people who lived after the African exodus, but before the split between Europeans and Asians.

Dr. Paabo and his colleagues also found that the Ust'-Ishim man had pieces of Neanderthal DNA in his genome, just as living non-Africans do. But his Neanderthal DNA has some important differences.

Fossils indicate that Neanderthals spread across Europe and Asia before becoming extinct an estimated 40,000 years ago. Today, the Neanderthal DNA in each living non-African human is broken up into short segments sprinkled throughout the genome.

Dr. Paabo and his colleagues have hypothesized that this arrangement is the result of how cells divide.

During the development of eggs and sperm, each pair of chromosomes swaps pieces of their DNA. Over the generations, long stretches of DNA get broken into smaller ones, like a deck of cards repeatedly shuffled.

Over thousands of generations, the Neanderthal DNA became more fragmented. Dr. Paabo and his colleagues predicted, however, that Neanderthal DNA in the Ust'-Ishim man’s genome would form longer stretches.

And that’s exactly what they found. “It was very satisfying to see that,” Dr. Paabo said.

By comparing the Ust'-Ishim man’s long stretches of Neanderthal DNA to shorter stretches in living humans, Dr. Paabo and his colleagues estimated the rate at which they fragmented. They used that information to determine how long ago Neanderthals and humans interbred.

Previous studies — based on only living humans — had yielded an estimate between 37,000 and 86,000 years. Dr. Paabo and his colleagues have now narrowed down that estimate dramatically: Humans and Neanderthals interbred between 50,000 and 60,000 years ago, according to the new data.

The findings raised questions about research suggesting that humans in India and the Near East dated back as far as 100,000 years ago. Some scientists believe that humans expanded out of Africa in a series of waves.

But Christopher Stringer, a paleoanthropologist at the National History Museum, said that the new study offered compelling evidence that living non-Africans descended from a group of people who moved out of Africa about 60,000 years ago.

Any humans that expanded out of Africa before then probably died out, Mr. Stringer said. “They made an insignificant contribution to modern humans.”