NEW YORK TIMES December 18, 2013
Toe Fossil Provides Complete Neanderthal Genome
By CARL ZIMMER
Scientists have extracted the entire genome of a 130,000-year-old Neanderthal from a single toe bone
in a Siberian cave, an accomplishment that far outstrips any previous work on Neanderthal genes.
The accuracy of the new genome is of similar quality to what scientists would achieve if they were
sequencing the DNA of a living person.
“It’s an amazing technical accomplishment,” said Sarah A. Tishkoff, an expert on human evolution at
the University of Pennsylvania, who was not involved in the research. “Twenty years ago, I would have
thought this would never be possible.”
The new Neanderthal genome, which is described in the current issue of Nature, is part of an
extraordinary flurry of advances in studying ancient human DNA. Earlier this month, for example,
scientists reconstructed a small segment of genes from a 400,000-year-old fossil in Spain, setting a
record for the oldest human DNA ever found.
While the Spanish DNA only provided faint, tantalizing clues about human evolution, the new
Neanderthal genome is more like a genetic encyclopedia, rich with new insights. The Neanderthal to
whom the bone belonged was highly inbred, for example, offering a glimpse into the social lives of
Neanderthals.
The new Neanderthal genome also contains evidence of more interbreeding between ancient human
populations than previously known.
The authors of the new study also compared the Neanderthal genome to modern human DNA to
better understand what makes our own lineage unique. They have come up with a list of mutations
that evolved in modern humans after their ancestors branched off from Neanderthals some 600,000
years ago.
“The list of modern human things is quite short,” said John Hawks, a paleoanthropologist at the
University of Wisconsin who was not involved in the study.
Neanderthals have intrigued scientists ever since their first fossils were found in 1856. Experts argued
whether they were part of our own species or a separate one. Since the initial discovery, researchers
have found remains of these heavy-browed, solidly built humans from Spain to Central Asia. Their
fossil record now stretches from about 200,000 years ago to about 30,000 years ago.
Some of these fossils still hold fragments of Neanderthal DNA. In 1997, Svante Paabo of the Max
Planck Institute for Evolutionary Anthropology and his colleagues extracted a snippet from a 40,000year-old Neanderthal fossil. In 2010, after gathering more DNA from fossils, Dr. Paabo’s team
published a rough draft of the entire Neanderthal genome.
Using improved methods, the scientists were able to reconstruct the genome from another trove of
DNA from an 80,000-year-old finger bone retrieved by a team of Russian explorers from a cave called
Denisova.
Much to their surprise, the genome belonged to a separate lineage of humans that had not been
known from the fossil record before. The scientists called these mysterious people the Denisovans.
By comparing the rough drafts of the Denisovan and Neanderthal genomes to modern human DNA,
Dr. Paabo and his colleagues found clues to how we’re all related. Modern humans, Neanderthals and
Denisovans all descended from a common ancestor that lived several hundred thousand years ago.
The ancestors of modern humans then branched away on their own lineage. It wasn’t until later that
Neanderthals and Denisovans split apart from each other.
The researchers also discovered some Neanderthal and Denisovan DNA in the genomes of living
humans.
Dr. Paabo and his colleagues concluded that modern humans interbred with both Neanderthals and
Denisovans before those two lineages became extinct.
The scientists then developed better methods for reconstructing ancient DNA. They were able to
create a new version of the Denisovan genome that was extremely accurate and complete.
There was just one catch: the latest reconstruction methods demanded a lot of ancient DNA, which is
a rare thing to find in fossils. But when Dr. Paabo and his colleagues studied more bones from
Denisova, they hit the jackpot again, discovering an abundance of DNA in a toe bone.
“We thought it would be a Denisovan toe,” said Dr. Paabo, “but it very clearly was a Neanderthal.”
The scientists were able to reconstruct the new Neanderthal genome even more accurately than the
Denisovan one.
The crisp focus of the new genome is yielding new discoveries about Neanderthals. For example, Dr.
Paabo and his colleagues can distinguish the origin of each piece of DNA — whether it came from the
Neanderthal’s mother or father. With an X chromosome from each parent, the toe belonged to a
female.
A closer look at these two sets of DNA revealed that the Neanderthal female was extremely inbred.
Her two parental sets of genes were identical for long stretches. Such similarity can only come about
when close relatives have children.
“We don’t know if this is typical of all Neanderthals, or just this population in Siberia,” said Dr. Paabo.
It will take more high-caliber Neanderthal genomes to settle that question.
The new genome reveals not just inbreeding but interbreeding. The accompanying diagram
summarizes the flow of DNA between human lineages over the past half million years, based on a
comparison of the new Neanderthal genome with other Neanderthal DNA sequences, the Denisovan
genome and the genomes of living humans.
Dr. Paabo and his colleagues were able to detect not one, but two injections of Denisovan DNA into
the modern human gene pool.
Intriguingly, the Denisovan genome also contains hints of even more exotic interbreeding. A few
percent of their DNA appears to have originated from a more distant branch of our evolutionary tree.
Dr. Paabo said it was possible that the branch was a species known as Homo erectus, which lived
across much of the Old World from 1.8 million to about 50,000 years ago.
Dr. Tishkoff thinks this is a possible explanation of the data, but not the only one. She thinks it is
possible that the same pattern could have emerged if the ancestors of humans, Neanderthals and
Denisovans in Africa became separated from each other early on, evolving different DNA sequences.
Despite all the flowing DNA, Neanderthals, Denisovans and modern humans did not become one big
genetic blur. After Denisovan and Neanderthal DNA made its way into the modern human gene pool,
most of it gradually disappeared. And modern humans took their own evolutionary path.
By comparing their high-quality ancient genomes to human genomes, Dr. Paabo and his colleagues
are drawing up a list of mutations that are unique to our own lineage. “I would say it is a definitive
list,” said Dr. Paabo.
Dr. Paabo is intrigued by some mutations that affect genes involved in the development of the brain.
But he sees the list as only a starting point for research.
“What lies ahead is to understand which of these is important,” said Dr. Paabo. “That’s totally up in
the air.”