Secrets of Denisovan DNA

Science Researchers Sequence the Genome of the Denisovans, A Close Relative of the Neandertals
by Kathy Wren and Natasha Pinol, Advanced Science Serving Society

August 30, 2012 -- Researchers have now described the complete sequence of the Denisovan genome, shedding light on the relationships between these archaic humans, who were closely related to Neandertals, and modern humans.

The research team, led by Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, generated a list of recent changes in the human genome that occurred after modern humans diverged from the Denisovans. This list will help scientists understand what sets modern humans apart from the Denisovans and Neandertals.

The results were published online by Science, in the 30 August edition of ScienceExpress.

Fossil evidence of the Denisovans is scanty; the existence of this group only came to light in 2010 when DNA from a piece of a finger bone and two molars that were excavated at Denisova Cave in the Altai Mountains of southern Siberia was studied.

"We’ve remarkably been able to extract DNA from the Neandertals and Denisovans to compare them to ourselves," said Laura Zahn, senior editor at the journal Science, during a 29 August press teleconference.

Because they had only a tiny sample of genetic material recovered from the finger bone, Pääbo and his research team developed a treatment that "unzipped" the ancient DNA so that each of its two strands could be used to generate molecules for sequencing. This method allowed the team to generate an extremely thorough genome sequence, similar in quality to what researchers can obtain for the modern human genome.

"We have very few errors in the sequences, even less errors than we often have when you sequence a person today," Pääbo said. "[This genome] now allows us to look across the whole genome on all the mutations that have happened since we separated from Denisovans... such mutations that happened very recently in human history and have spread to everybody or almost everybody today."

The researchers compared the Denisovan genome with the genomes of several modern humans from around the world. The Denisovans share more genes with populations from the islands of southeastern Asia, including Melanesia and Australian Aborigines, than with populations elsewhere in Asia.

"We can confirm... that relatives of a Denisovan individual in Denisova Cave contributed genes to the ancestors of present-day people from New Guinea, in a gene flow event that did not affect the rest of the people in mainland Eurasia," said David Reich of Harvard Medical School and the Broad Institute in Massachusetts. "We find no trace of Denisovan genetic material in mainland Eurasia, including in mainland Southeast Asia, to the limits of our resolution."

"However, it’s clear that Denisovan genetic material has contributed 3-5% of the genomes of people in Australia and New Guinea and Aboriginal people from the Philippines and some of the islands nearby," Reich noted, "so we are able to confirm that quite powerfully."

The research team, which published a draft sequence of the Neandertal genome in 2010, uncovered another surprise with the Denisova genome. "What seems to be the case is that people in the eastern parts of Eurasia, in Native Americans, have more Neandertal material than people in Europe, even though Neandertals mostly lived in Europe," Reich said, "which is really, really interesting, and we were not able to detect this before in our paper we published in 2010."

The researchers also concluded that the Denisovan individual whose genome was sequenced carried genetic variants that in present-day humans are associated with dark skin, brown hair, and brown eyes, and that the genetic diversity of the Denisovans themselves was extremely low.

"By doing some more sophisticated analysis, one could actually track back the genetic diversity through time, and it became apparent that the genetic diversity was low over the last few hundred thousand years of the Denisovan history," said Matthias Meyer of the Max Planck Institute for Evolutionary Anthropology.

Given the Denisovans’ wide geographic range over time, it’s likely that their population was initially quite small but grew quickly, without time for genetic diversity to increase.

If further research shows that the Neandertal population size changed over time in a similar way, that may suggest that a single population expanding out of Africa gave rise to both the Denisovans and Neandertals, the study authors say.

http://www.aaas.org/news/releases/2012/0830sp_denisova.shtml