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Identifying Denisovan remains from protein analysis when DNA isn't present. Article from May of 2019.

<Biggest Denisovan fossil yet spills ancient human’s secrets

Jawbone from China reveals that the ancient human was widespread across the world — and lived at surprising altitude.

Matthew Warren

A Denisovan jawbone was discovered on Tibetan Plateau at an altitude of more than 3,000 metres.Credit: Dongju Zhang, Lanzhou University

Scientists have uncovered the most complete remains yet from the mysterious ancient-hominin group known as the Denisovans. The jawbone, discovered high on the Tibetan Plateau and dated to more than 160,000 years ago, is also the first Denisovan specimen found outside the Siberian cave in which the hominin was uncovered a decade ago — confirming suspicions that Denisovans were more widespread than the fossil record currently suggests.

The research marks the first time an ancient human has been identified solely through the analysis of proteins. With no usable DNA, scientists examined proteins in the specimen’s teeth, raising hopes that more fossils could be identified even when DNA is not preserved.

Siberia’s ancient ghost clan starts to surrender its secrets “This is fantastic work,” says Katerina Douka, an archaeologist at the Max Planck Institute for the Science of Human History in Jena, Germany, who runs a separate project aiming to uncover Denisovan fossils in Asia. “It tells us that we are looking at the right area.”

Hunting for DenisovansUntil now, everything scientists have learnt about Denisovans has come from a handful of teeth and bone fragments from Denisova Cave in Russia’s Altai Mountains. DNA from these remains revealed that the Denisovans were a sister group to Neanderthals, both descending from a population that split away from modern humans about 550,00–765,000 years ago. And at Denisova Cave, the two groups seem to have met and interbred: a bone fragment described last year belonged an ancient-human hybrid individual who had a Denisovan father and Neanderthal mother.

But many expected that it was only a matter of time before researchers found evidence of Denisovans elsewhere. Some modern humans in Asia and Oceania carry traces of Denisovan DNA, raising the possibility that the hominin lived far away from Siberia. And some researchers think that unclassified hominin fossils from China could be Denisovan.

The latest specimen, described in Nature 1, consists of half a lower jaw, with two complete teeth. A monk found it in Baishiya Karst Cave in China in 1980, and passed on to Lanzhou University. But it wasn’t until the 2010s that archaeologist Dongju Zhang and her colleagues began studying the bone.

The team faced a problem. The Denisova Cave remains had all been identified because they still contained some DNA, which could be compared with genetic sequences from other ancient humans. But there was no DNA left in the jawbone.

Instead, the scientists looked for ancient proteins, which tend to last longer than DNA. In dentine from the teeth, they found collagen proteins suitable for analysis. The team compared these with equivalent proteins in groupsincluding Denisovans and Neanderthals, and found that they lined up closest with sequences from Denisovans.

The team were also able to piece together other snippets of information about the individual. One of the teeth was still erupting, for example, leading the authors to speculate that the jawbone belonged to an adolescent.

A virtual reconstruction of the jawbone.Credit: Jean-Jacques Hublin, MPI-EVA, Leipzig

Previous research 2 identified Neanderthal remains using both proteins and DNA — but the success of the latest study could lead to a greater emphasis on getting ancient proteins out of fossils that haven’t yielded DNA, says Chris Stringer, a palaeoanthropologist at the Natural History Museum in London. The method could prove particularly useful for older samples or those from southeast Asia and other warm climates, where DNA degrades quickest.

But the field is still in its early stages, Stringer adds, and ancient-protein analysis currently has a smaller sample of early hominins for comparison than does DNA analysis. “Although it’s certainly very suggestive of a link with the Denisovans, I think I’d like to see bigger samples to really pin that down more,” he says.

Douka agrees: for now, ancient DNA analysis remains the “gold standard” for this kind of work, she says. Although there is no genetic material in the jawbone, Douka wonders whether researchers could still find DNA in the Tibetan cave — perhaps in sediment.

The Roof of the WorldThe altitude of the new Denisovan’s home — 3,280 metres above sea level — surprised researchers, and helps to solve a mystery about Denisovans’ genetic contribution to modern Tibetans (see ‘Denisovan hang-outs’). “It is astonishing that any ancient humans were at that altitude,” says Stringer.

Some Tibetans have a variant of a gene called EPAS1 that reduces the amount of the oxygen-carrying protein haemoglobin in their blood, enabling them to live at high altitudes with low oxygen levels. Researchers 3 had thought that this adaptation came from Denisovans, but this was difficult to reconcile with Denisova Cave’s relatively low altitude of 700 metres. The latest study suggests that Denisovans evolved the adaptation on the Tibetan Plateau and passed it to Homo sapiens when the species arrived around 30,000–40,000 years ago, says co-author Frido Welker, a molecular anthropologist at the University of Copenhagen. If Denisovans in Asia were adapted to high altitudes, similar sites could harbour more of their remains.

Mum’s a Neanderthal, Dad’s a Denisovan: First discovery of an ancient-human hybrid He points to Sel’Ungur cave in Kyrgyzstan, about 2,000 metres above sea level, where a hominin child’s arm bone was found but did not yield any DNA. “Now I ask myself — maybe that specimen is also a Denisovan and not a Neanderthal, like we usually assume,” says Bence Viola, a palaeoanthropologist at the University of Toronto in Canada.

Re-evaluating fossils? And the fossil is likely to prompt scientists to reconsider the classification of other remains. “We can kind of work ourselves through the fossil record, and link up more and more specimens with the Denisovans,” says Viola.

One? candidate is a jawbone known as Penghu 1, which was caught in a fishing net near Taiwan and has many similarities to the latest mandible. Welker and his colleagues hypothesize that this jaw could be Denisovan — but the ultimate proof will come from DNA or protein analysis, says Welker.

Sampling any remains for proteins or DNA is by its nature destructive, so there must good justification for doing so, he adds. “It’s not a light-hearted decision to make.”

Nature 569, 16-17 (2019)

doi: 10.1038/d41586-019-01395-0


1.Chen, F. et al. Nature (2019).

Article Google Scholar2.Welker, F. et al. Proc. Natl Acad. Sci. USA 113, 11162–11167 (2016).

PubMed Article Google Scholar3. Huerta-Sánchez, E. et al. Nature 512, 194–197 (2014).>
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