Waking the Dead

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Waking the Dead

http://news.ku.dk/all_news/2010/2010.2/human_genome/

Scientists at the University of Copenhagen have become the first to reconstruct

the nuclear genome of an extinct human being. It is the first time an ancient

genome has been reconstructed in detail. The innovative technique can be applied

to museum materials and ancient remains found in nature and can help

reconstructing human phenotypic traits of extinct cultures from where only

limited remains have been recovered. It also allows for finding those

contemporary populations most closely related to extinct cultures revealing

ancient human expansions and migrations. Finally, the discovery improves our

understanding of heredity and the disease risk passed down from our ancestors.

The spectacular results of the research are being published in the upcoming

issue of Nature.

Professor Eske Willerslev and his PhD student Morten Rasmussen, from Centre of

Excellence in GeoGenetics at the Natural History Museum, University of

Copenhagen, Denmark, led the international team of scientists responsible for

the findings.

Sequencing the genome

Professor Willerslev, 38, and his team grabbed international attention last year

when they reconstructed the complete mitochondrial genomes of a woolly mammoth

and an ancient human. However, the current discovery is the first time

scientists have been able to reconstruct the 80% of the nuclear genome that is

possible to retrieve from fossil remains. From the genomic sequences, the team

has managed to construct a picture of a male individual who lived in Greenland

4,000 years ago and belonged to the first culture to settle in the New World

Arctic.

The discovery was made by analysing a tuft of hair that belonged to a man from

the Saqqaq culture from north-western Greenland 4,000 years ago. The scientists

have named the ancient human " Inuk " , which means " man " or " human " in

Greenlandic. Although Inuk is more closely related to contemporary north-eastern

Siberian tribes than to modern Inuits of the present day New World Arctic, the

scientists wants to acknowledge that the discovery was made in Greenland.

Professor Willerslev discovered the existence of the hair tuft by coincidence

after several unsuccessful attempts to find early human remains in Greenland

" I was speaking with the Director of the Natural History Museum in Denmark, Dr.

Morten Meldgaard, when we started discussing the early peopling of the Arctic, "

Willerslev recalls. " Meldgaard who had participated in several excavations in

Greenland told me about a large tuft of hair, which was found during an

excavation in north-western Greenland in the 1980's and now stored at the

National Museum in Denmark.

" After the Greenland National Museum and Archives granted permission, we

analysed the hair for DNA using various techniques and found it to be from a

human male. For several months, we were uncertain as to whether our efforts

would be fruitful. However, through the hard work of a large international team,

we finally managed to sequence the first complete genome of an extinct human. " ,

Willerslev says.

Willerslev adds: " It was crucial that a private person, Fredrik sen,

chairman of the medical company Ferring, became interested in the project and

provided the necessary funding to run some pilot tests, and that The Lundbeck

Foundation of Denmark, quickly followed up providing substantial economic

support to complete the project " .

" It shows how crucial private funding is to basic science these days. Without

these private donors it would have taken us a lot longer to sequence the first

ancient human genome " .

Blueprint of the ancient man

The reconstruction serves as blueprint that scientists can use to give a

description of how the pre-historic Greenlander, Inuk, looked - including his

tendency to baldness, dry earwax, brown eyes, dark skin, the blood type A+,

shovel-shaped front teeth, and that he was genetically adapted to cold

temperatures, and to what extend he was predisposed to certain illnesses. This

is important as besides four small pieces of bone and hair, no human remains

have been found of the first people that settled the New World Arctic.

Willerslev's team can also reveal that Inuk's ancestors crossed into the New

World from north-eastern Siberia between 4,400 and 6,400 years ago in a

migration wave that was independent of those of Native Americans and Inuit

ancestors. Thus, Inuk and his people left no dependence behind among

contemporary indigenous people of the New World.

" Previous efforts to reconstruct the mammoth nuclear genome resulted in a

sequence filled with gaps and errors due to DNA damage because the technology

was in its infancy. The genome of Inuk is comparable in quality to that of a

modern human " , Willerslev tells and continues:

" Our findings can be of significant help to archaeologists and others as they

seek to determine what happened to people from extinct cultures. Doing so

requires organic material - bones or hair kept as museum pieces or found at

archaeological sites. Previously, the DNA needed to have been frozen or buried

in a layer of permafrost. But with the new methods developed here at the Centre,

that is not a premise anymore " .

Much of the hands-on work analysing and joining the DNA sequences and the

chemical analyses of what little was left of the damaged genetic material

together to form a complete profile of Inuk was done by Morten Rasmussen. The

work was carried out in close collaboration with other scientists at the

University of Copenhagen and in China, where they have far more sequencing

machines than in Denmark.

" Not so long ago, reconstructing an entire modern human genome took years, "

Rasmussen says. But the new methods and the abundance of sequencing machines

allow us to do it in just a few months - and that includes the time-consuming

task of analysing the results. The interesting thing about compiling a human

genome is that we can look at the genes to see traits like why Scandinavians are

blonde, why some are predisposed to certain illnesses and why others more easily

become addicted to alcohol or tobacco. But the genome we've reconstructed is no

enstein's Monster; it's more like we've got the blueprints for a house, but

we don't know how to build it. "

The results of the team's research will be published in the leading British

scientific journal Nature.

Key collaborators:

Anders Krogh's bioinformatics group, University of Copenhagen, Denmark

Søren Brunak and Sicheritz-Ponten's bioinformatics groups, Technical

University of Denmark

Rasmus Nielsen's evolution group, University of California, Berkeley, US

Villem's genetic anthropology group, Latvia

Toomas Kivisild's genetic anthropology group, Cambridge, UK

Jun Wang's sequencing centre, BGI, China

Bjarne Grønnow, National Museum of Denmark, Denmark

Claus sen, Greenland National Museum and Archives, Greenland