From a tiny bone, clues to a new human

By Leah Eisenstadt, Broad Communications, December 23rd, 2010
  • A tooth discovered in Denisova Cave in southern Siberia is from a
    new class of hominin, the Denisovans
    Image courtesy of Max Planck Institute for Evolutionary Anthropology,
    Leipzig, Germany

In 2008, a team of archaeologists was excavating in Denisova Cave, located in the Altai Mountains in southern Siberia, when they discovered a small finger bone at least 30,000 years old. The team put the bone in a box labeled “modern human” and sent it for analysis by scientists in the laboratory of Svante Pääbo at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Although the bone was not thought to be extraordinary, Pääbo’s team analyzed the bone’s mitochondrial DNA, which is passed down from mother to child and could reveal secrets about the identity of the bone’s owner.

Earlier this year, the scientists published their astounding discovery about the bone: it belonged to neither a Neandertal nor a modern human, the two main hominin forms living at the time. Now, from work led by Pääbo, along with David Reich, associate professor of genetics at Harvard Medical School and an associate member of the Broad Institute, the sequence of the bone’s nuclear DNA reveals that it belonged to a member of a new class of hominin never before recognized, which the team has named the Denisovans. In addition to enriching the picture of hominin diversity at the time, the work, which appears in the December 23 issue of Nature, also uncovers more evidence of a close relationship between anatomically modern humans living at the time and other hominin types, leaving imprints on our genome that persist today.

When the bone was first discovered, archaeologists knew it was very old and from a juvenile hominin, but they couldn’t tell from its shape or size whether it was from a modern human, a Neandertal, or something else. After the mitochondrial DNA analysis revealed it was unique, scientists were shocked. “The discovery of DNA like this is really shocking to people who study these things all the time,” said Reich, who was not involved in the initial study. “It’s out of the ballpark.”

Paabo and his colleagues next set out to sequence the nuclear genome of the new hominin, for comparison to genomes of modern humans and the Neandertal, sequenced earlier this year both at the Max Planck Institute and at the Broad Institute. Ancient DNA is typically difficult to analyze, due to several challenges. First, a sample must have enough DNA to be sequenced. “That’s very hard to find,” said Reich, who led the data analysis effort in the new study. Luckily, genetic material from the finger bone was in extremely good condition, comparable in quality to samples of DNA taken from humans living today. “This is the best-preserved, non-permafrost sample that’s ever been found from this time period,” he said. Another problem stems from contamination by microbes, whose DNA can cloud the sample. In this case, microbial contamination was very low. Additionally, ancient DNA is often damaged over time, and Pääbo’s group recently developed a technique to deal with that damage.

The quality of the finger bone DNA enabled the scientists to achieve a high 1.9-fold coverage of the genome during sequencing, compared to 1.3-fold for the Neandertal genome. “We feel incredibly fortunate,” said Nick Patterson, a Broad researcher and co-first author on the new work. “For all we know, this is the only bone we’ll ever get like this.”

After generating relatively high-quality DNA sequence from the finger bone, the scientists compared it to the genomes of modern humans and Neandertals and saw different patterns in the bone’s genome. This is strong evidence that it belongs to a new class of hominin that shared common ancestry with Neandertals several hundred thousand years ago. Additionally, the research team in Russia discovered an adult tooth in the Denisova Cave that had physical features unlike those of teeth from any known hominins, supporting the conclusion that it came from another member of this new class.

The earlier study on Neandertals showed that these hominins interbred with modern humans at some point and left an imprint on the genome of all non-Africans living today, with 1-4% of their genome derived from that of Neandertal. When the research team compared the Denisovan genome to that of various modern human populations living today, they saw evidence of another “gene flow” event — the integration of genetic material from one population into another. In the genome of people living in Melanesia, an area including Papua New Guinea and Bougainville Island, the team discovered signs that Denisovans interacted with the Melanesian ancestors. Today, 4-6% of the genome of Melanesian people is derived from genetic material related closely to the Denisovan hominin, in addition to the portion derived from Neandertals seen in all non-Africans.

The very large geographical distance between Denisova Cave in southern Siberia and the likely migration path of modern humans as they left Africa to colonize Melanesia more than 45,000 years agoleads the research team to suspect that the Denisovans had a broader range than even the Neandertals. “That’s perhaps one of the most exciting things to emerge from this,” said Reich. “There’s a Neandertal-like population which was not just living in Denisova Cave, but which had a huge range if it interacted with the ancestors of Melanesians.”

Reich added that the new finding suggests an even greater diversity of humans living at the time, including modern humans, Neandertals, the “hobbits” of Flores island, and Denisovans. The scientists hope that more Denisovan fossils or artifacts may be found in the future, and that previously unidentified or misidentified materials, such as some particularly “confusing” fossils from East Asia, might be reexamined in light of the new findings. “I’m hoping that archaeologists will revisit the record and reinterpret it,” said Patterson.

Along with the earlier Neandertal findings, this new work provides more evidence of gene flow and close interaction between archaic hominins and modern humans, something not broadly accepted in the genetics community until recently, according to Reich. He said it’s plausible that other unknown archaic groups interacted with modern humans, but scientists have yet to discover DNA from those groups to probe. “This work is changing views of how common gene flow was in evolution,” he said.

The work also represents a shift in the view of genetics in the field of archaeology. “Perhaps the most interesting thing that comes from this is that the genetics suggests that there’s an interesting archaeological and fossil record to find,” said Reich. Normally, an unusual skull or skeleton would stimulate the genetic research, but in this case it may be reversed. “We have next to nothing in terms of bones. We don’t have a skull. We have just a finger bone and a tooth,” said Reich. “And now we have a genome, and the genome tells us a lot.” For the Denisovans, more evidence may yet be found that can help reveal the history of our new, strange cousin and help us see the origins of our own genome more clearly.

Paper(s) cited: 
Reich et al., Genetic history of an archaic hominin group from Denisova Cave in southern Siberia Nature. December 23, 2010. DOI: 10.1038/nature09710