30 August 2012

Denisovans, an ancient human group, have genome mapped

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The complete genome of Denisovans – an ancient human group that lived at the same time as Neanderthals – has been sequenced using a tiny finger bone and a new, cutting-edge technique offering unprecedented accuracy.
Denisova Cave excavation – Denisovan genome sequence.

Researchers excavating in Denisova Cave in southern Siberia, where the Denisovan remains were discovered in 2008. Credit: Max Planck Institute for Evolutionary Anthropology

Finger bone – Denisovan genome sequence.

A replica of the Denisovan finger bone from which the entire Denisovan genome was sequenced, placed on a modern human's hand. Credit: Max Planck Institute for Evolutionary Anthropology

Molar – Denisovan genome sequence.

One of two Denisovan teeth also discovered in the cave in Siberia. Credit: Max Planck Institute for Evolutionary Anthropology

Denisova cave – Denisovan genome sequence.

Outside the Denisova Cave in southern Siberia, where the Denisovan remains were discovered in 2008. Credit: Max Planck Institute for Evolutionary Anthropology

SYDNEY: The complete genome of a Denisovan – an ancient human that lived at the same time as Neanderthals – has been sequenced using a tiny finger bone and a new, cutting-edge technique offering unprecedented accuracy.

As a result of the new technique and an extremely well preserved bone, the sequence is more precise than the famous culmination of the Human Genome Project published in 2003 – and on par with what is achievable when sequencing modern humans today.

“There is actually today no difference in what we can learn genetically about a person that lived 50,000 years ago and from a person today, provided that we have well-enough preserved bones,” Svante Pääbo, paper co-author and a geneticist from the Max Planck Institute for Evolutionary Anthropology in Germany, said in a press conference.

Papuans have 6% Denisovan DNA

Using the DNA, the researchers dated the Denisovan remains, which appear to have belonged to a female child, who died between 74,000 and 82,000 years ago. The findings, which were the result of a massive international collaboration involving more than 30 scientists, are published in the journal Science.

The new research adds evidence to the recently challenged theory that our species, Homo sapiens, interbred with Neanderthals as well as, it now seems, Denisovans.

While Neanderthals contributed to the DNA of all modern humans excluding indigenous Africans, Denisovan DNA can only be found in people indigenous to Papua New Guinea, Fiji, Australia and other parts of Melanesia. In fact, the researchers estimate that up to 6% of the genomes of modern-day Papuans derive from Denisovans.

Different human groups, not species

The new research also confirmed earlier studies that showed the Denisovan individual carried the same genes that are today associated with having dark skin, brown hair and brown eyes.

“However, since we have access to only a single Denisovan individual, we expect that only a subset of these would have been shared among all Denisovans,” the researchers wrote in the paper. In other words, the little girl may simply have had dark hair and eyes, traits that may not have been shared by all Denisovans.

Pääbo said that he avoids referring to archaic humans, such as Denisovans, as separate species, during a press conferences

“We say it’s a different group of humans,” he said. “[Denisovans] are about as different from Neanderthals … as people in Africa would be from people in Scandinavia. I wouldn’t call the Neanderthals a different species from [modern] humans, either, actually,” he added.

Revolutionary new sequencing technique

While tiny, the Denisovan fingertip bone discovery was an enormous stroke of luck. The bone turned out to contain 70% ‘endogenous’ DNA – DNA belonging to the owner of the finger, and not to bacteria and other contaminants. That is compared to an average of about 1–5% endogenous DNA in other ancient human remains.

This, combined with the innovative technique that allows geneticists to sequence from single-stranded DNA, meant the researchers could map the Denisovan genome with an extremely high ‘coverage’, or accuracy – better than anything achieved with Neanderthals, despite the much larger volume of Neanderthal remains available.

‘Coverage’ in genome sequencing refers to the average number of times each DNA base is sequenced – the higher the number, the higher the overall accuracy. The Denisovan genome was sequenced with 30-fold coverage. By comparison, when the first human genome was sequenced in 2003, it had a 10-fold coverage. For the first draft of the Neanderthal genome presented in 2010, each DNA base was sequenced just once on average.

“This new sequencing technology brings tears to my eyes,” said David Lambert, a geneticist and evolutionary biologist from Griffith University in Queensland, Australia. Lambert wasn’t involved with the Denisovan research, but is working on sequencing the genomes of the oldest human remains found in Australia. “Technology like this is very important to us. Let’s hope it’ll be a major assistance,” he said.

Genomes are best sequenced from whole, double-stranded DNA. However, DNA found in ancient remains has usually degraded over time to fragmented strands. The new technique works by manipulating these ancient DNA fragments by attaching artificial ‘adapters’ from which the fragments can be copied or ‘amplified’.

“By doing this, we kind of succeeded to develop a more efficient way of extracting information from the few DNA fragments preserved in the bone,” explained another paper co-author Matthias Meyer, also from the Max Planck Institute.

Denisovan population declined as Homo sapiens numbers grew

Using this new technique, the researchers were also able to track the genetic diversity of the Denisovans and therefore any historic fluctuations in population numbers. A striking find was that around the same time modern-day human populations spiked, between 125,000 and 150,000 years ago, Denisovan population saw a “drastic decline”, researchers said in the paper.

Based on the findings of this population “bottleneck”, “it is tempting to think that there was an interaction between the two [human groups],” said Lambert.

The research paper also pinpointed certain genes that were fixed in modern humans after the divergence from our ancient relatives between 170,000 and 700,000 years ago.

“It is very interesting that a lot of those genes are important in terms of things like brain function and the the nervous system,” said Lambert. “Things like that are really starting to give us a much better idea of what it means to be Homo sapien.”

The scant remains of the Denisovan girl were discovered in the remote Denisova Cave in the Altai Mountains, southern Siberia, in 2008. Originally thought to belong to a Neanderthal variant, the remains turned out to be that of a previously unknown type of human, which was named after the discovery site.

Denisovans represent the first time an extinct group of humans has been defined as such from DNA sequencing alone, and not from the form and structure of the bones. The researchers said they hope to sequence the Neanderthal genome to a similar level of accuracy and coverage using the new technique within a year.

“I would also not be totally surprised if in the future one finds other groups of humans in addition to Neanderthals and Denisovans out there, particularly in Asia,” said Pääbo.

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