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Denisovan - Humpath.com - Human pathology

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Wednesday 26 December 2012

Researchers have sequenced the genome of an archaic Siberian girl 31 times over, using a new method that amplifies single strands of DNA.

More than 99% of the nucleotides are sequenced at least 10 times, so researchers have as sharp a picture of this ancient genome as of a living person’s.

That precision allows the team to compare the nuclear genome of this girl, who lived in Siberia’s Denisova Cave more than 50,000 years ago, directly to the genomes of living people, producing a "near-complete" catalog of the small number of genetic changes that make us different from the Denisovans, who were close relatives of Neandertals.

In 2011, the same lab shared our spotlight for piecing together the genome of the Denisovans, an archaic human that lived in Siberia at least 50,000 years ago.

But those ancient DNA sequences and others were blurry snapshots next to the high-resolution genomes that researchers can now sequence from living people.

Much of the fragile DNA from fossils is degraded into single strands that automatic sequencers can’t copy.

Researchers were resigned to deciphering only parts of the code of ancient genomes, whether from archaic humans, animals, or pathogens.

In 2012, however, a persistent postdoc developed a remarkable new method that enabled his team to revisit the Denisovan DNA and sequence it 31 times over.

The resulting genome, of a girl who lived in Siberia’s Denisova Cave, reveals her genetic material in the same sharp, rich detail that researchers typically get from the DNA of living people.

This technological feat promises to give a major boost to the field of ancient DNA, as researchers begin to apply the method to other samples and species.

Ancient DNA researchers typically have adapted the tools used to sequence DNA from living humans, which start with samples of double-stranded DNA. But ancient DNA usually breaks into single strands.

So postdoc Matthias Meyer at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, set out to sequence single-stranded ancient DNA from scratch.

He failed at first, but then managed to bind special molecules to the ends of a single DNA strand, holding it in place for sequencing.

As a result, using only 6 milligrams of bone from the Siberian girl’s pinky finger, Meyer and colleagues were able to copy 99.9% of her genome at least once and 92% of the genome 20 times—the benchmark for reliably identifying nucleotide positions.

The results confirmed that Denisovans interbred with the ancestors of some living humans; people living in parts of island Southeast Asia have inherited about 3% of their nuclear DNA from Denisovans.

The genome literally offers a glimpse of the girl, suggesting that she had brown eyes, brown hair, and brown skin.

It also allowed the team to use DNA to estimate that the girl died between 74,000 and 82,000 years ago—the first time researchers had used genomic information to date an archaic human.

The high quality of the genome gives researchers a powerful new tool to fish for genes that have recently evolved, providing a “near-complete” catalog of the handful of genetic changes that separate us from Denisovans, who were close kin to Neandertals.

These details are all the more remarkable because the Denisovans are so poorly known from fossils: Only a tiny scrap of finger bone and two molars have been reliably assigned to them so far.

In contrast, the Neandertals are known from hundreds of fossils but from a much less complete genome.

Neandertal experts may catch up soon. Meyer and colleagues have been trying “Matthias’s method” on fossil samples that previously failed to yield much DNA. A detailed Neandertal genome comparable to the Denisovan one is expected in 2013.


- A High-Coverage Genome Sequence from an Archaic Denisovan Individual. Matthias Meyer et al. Science 12 October 2012: Vol. 338 no. 6104 pp. 222-226. DOI: 10.1126/science.1224344

- A Crystal-Clear View of an Extinct Girl’s Genome!. Ann Gibbons. Science 31 August 2012: Vol. 337 no. 6098 pp. 1028-1029. DOI: 10.1126/science.337.6098.1028