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International Team Sequences Ancient Hominin Genome

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – In a paper appearing in today's issue of Nature, an international research group reported that it has sequenced the draft nuclear genome of a 30,000 to 50,000-year-old hominin belonging to a group distinct from both Neanderthals and humans.

The researchers used DNA extracted from a finger bone fragment found in Russia's Denisova Cave in 2008 to sequence the genome. Through comparisons with human, Neanderthal, and chimpanzee sequences, the team found evidence supporting their previous claim that this "Denisovan" individual represents an ancient hominin group that is neither human nor Neanderthal.

Even so, they found, Denisovans do share some sequences with present day populations in Papua New Guinea, hinting at inter-breeding between Denisovans and the ancestors of modern-day Melanesians.

"In combination with the Neanderthal genome sequence, the Denisovan genome suggests a complex picture of genetic interactions between our ancestors and different ancient hominin groups," senior author Svante Pääbo, director of the Max Planck Institute for Evolutionary Anthropology's evolutionary genetics department, said in a statement.

Earlier this year, Pääbo and his colleagues sequenced and analyzed the Denisovan individual's mitochondrial genome, garnering evidence indicating that it belonged to a previously unrecognized ancient hominin group.

Now, the team used the Illumina Genome Analyzer IIx to sequence the ancient female's nuclear genome to around 1.9 times coverage from well-preserved DNA found in a fragmented piece of finger bone.

They also used sequence capture-based sequencing to sequence the mitochondrial genome from a tooth found in the same cave as the finger bone to an average of 58 times coverage. The tooth was morphologically distinct from other hominin teeth, they noted, but its mitochondrial genome sequence differed from the finger bone mitochondrial genome at just two sites.

By comparing the newly sequenced Denisovan genome with human, Neanderthal, and other sequences, the researchers were able to place the Denisova individual within the hominin tree, showing that she came from an ancient group that was likely more closely related to Neanderthals than to ancient humans.

Based on the evidence available so far, they suspect that a hominin group that left Africa some 300,000 to 400,000 years ago eventually diverged into a Neanderthal group that eventually ended up in Europe and a Denisovan group, which migrated to Asia.

The researchers estimate that the Denisova and Neanderthal sequences diverged from one another around 640,000 years ago, while Denisovans diverged from human populations in Africa more than 800,000 years ago.

Even so, they noted, modern humans who left Africa around 70,000 to 80,000 years ago seem to have interacted with Neanderthals and, more recently, with Denisovans.

When researchers compared the Denisova sequence with sequence patterns in more than four-dozen modern day human populations from parts of Africa, Melanesia, and elsewhere, they uncovered sequences that are shared between the Denisovans and some Melanesian populations living in Papua New Guinea today.

Their findings suggest that as much as four to six percent of some Melanesian genomes are comprised of Denisovan-derived sequence — a relationship that parallels the apparent inter-breeding between Neanderthals and non-African humans reported by Pääbo and his co-workers in Science this past spring.

"Instead of the clean story we used to have of modern humans migrating out of Africa and replacing Neanderthals, we now see these very intertwined story lines with more players and more interactions than we knew of before," co-lead author Richard Green, an evolutionary genetics and biomolecular engineering researcher affiliated with the University of California at Santa Cruz and the Max Planck Institute, said in a statement.

"[W]e would like to know much more about the Denisovans and their interactions with human populations," he added. "And you have to wonder if there were other populations that remain to be discovered."

Moreover, this finding offers additional clues about when and where these ancient hominins lived, hinting that they may have been found across East Asia during the Late Pleistocene period.

Indeed, the researchers argued that "on the Eurasian mainland there existed at least two forms of archaic hominins in the Upper Pleistocene: a western Eurasian form with morphological features that are commonly used to define them as Neanderthals, and an eastern form to which the Denisova individuals belong."

"In the future, when more complete genomes from these and other archaic hominins will be sequenced from remains that allow more morphological features to [be] assessed, their relationships will become even better understood," they concluded.

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