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Denisovan Genetic Analysis Uncovers Long History in Altai Mountains

NEW YORK (GenomeWeb) – Researchers have analyzed the genetic makeup of a fourth Denisovan individual, one much older than the three previously analyzed.

The Max Planck Institute for Evolutionary Anthropology's Svante Pääbo and his colleagues sequenced the first Denisovan genome in 2010. Only two other Denisovan samples have been uncovered since then.

As they reported today in Science Advances, Pääbo and his colleagues have now sequenced a fourth Denisovan sample that hails from the same cave in the Altai Mountains of Siberia, though from an older rock layer. This Denisovan individual was female and was some 50,000 years to 100,000 years older than the other Denisovan samples, which suggests that Denisovans lived near the Siberian cave for a long time.

"Beyond reinforcing the idea that both Neanderthals and Denisovans lived in the cave or its vicinity, our findings indicate that Denisovans were present over an extended period in the Altai region, where the two archaic groups may have met and mixed," the researchers wrote in their paper.

This new Denisovan sample, dubbed Denisova 2, is a deciduous molar tooth that was found in the Denisova cave in 1984 in a rock layer that's estimated to be 128,000 years to 227,000 years old. Based on the stratigraphy of the site, the researchers noted that Denisova 2 is one of the oldest hominin remains uncovered at the cave.

The researchers extracted DNA from the sample and analyzed part of it to estimate the frequency of cytosine-to-thymine substitutions — a feature of ancient DNA. They found that the sample likely contained authentic ancient DNA.

The other aliquot was converted into a single-stranded DNA library and underwent enrichment for mitochondrial DNA. It was then sequenced to an average 51X coverage.

A phylogenetic tree clustered this new Denisova 2 mtDNA genome with the three other Denisovan mtDNA genomes, though it differed from the other Denisovan mtDNA genomes by 29, 70, and 72 nucleotides, respectively. Additionally, they noted that the Denisova 2 mtDNA genome is more similar to that of Denisova 8. The researchers estimated that the Denisova 2 sample is some 20,600 years to 37,700 years older than the Denisova 8 sample, and that it is 54,200 years to 99,400 years older than the Denisova 3 sample.

This suggested to the researchers that Denisovans lived in and around the Altai Mountains for tens of thousands of years.

Pääbo and his colleagues also sequenced the nuclear genome of their new Denisovan sample — generating only 47 megabases — and aligned it to the human reference genome. Judging by the ratio of sequence coverage per base between the autosomes and the X chromosome, they determined that their sample belonged to a female Denisovan.

At the same time, the researchers examined sequence diversity among these four Denisovan samples. They found that sequence diversity among Denisovans was comparable to that among Neanderthals, but is in the lower range of what's observed in modern humans. However, the researchers noted that all the Denisovan samples come from one site. The estimate, then, could reflect the genetic diversity of an isolated Denisovan population and the wider Denisovan population might have been more diverse.

"Additional Denisovans from other locations are needed to more comprehensively gauge their genetic diversity across space and time," Pääbo and his colleagues wrote.