The Alan Sondheim Mail Archive

February 14, 2009

---------- Forwarded message ----------
Date: Sat, 14 Feb 2009 00:25:22 -0500
From: moderator@PORTSIDE.ORG
Subject: Draft Version of the Neanderthal Genome Completed

Draft Version of the Neanderthal Genome Completed

      Scientists they have completed a first draft
      version of the Neandertal genome.

(Feb. 12, 2009)

The announcement is being made by the Max Planck
Institute for Evolutionary Anthropology, in Leipzig,
Germany, and the 454 Life Sciences Corporation, in
Branford, Connecticut, on 12 February during the 2009
Annual Meeting of the American Association for the
Advancement of Science (AAAS) and at a simultaneous
European press briefing.

The project, made possible by financing from the Max
Planck Society, is directed by Prof. Svante Pääbo,
Director of the Institute's Department of Evolutionary
Genetics and Anthropology. Pääbo and his colleagues
have sequenced more than one billion DNA fragments
extracted from three Croatian Neandertal fossils, using
novel methods developed for this project. The
Neandertal genome sequence will clarify the
evolutionary relationship between humans and
Neandertals as well as help identify those genetic
changes that enabled modern humans to leave Africa and
rapidly spread around the world, starting around
100,000 years ago.

Neandertals were the closest relatives of currently
living humans. They lived in Europe and parts of Asia
until they became extinct about 30,000 years ago. For
more than a hundred years, paleontologists and
anthropologists have been striving to uncover their
evolutionary relationship to modern humans.

Pääbo, a pioneer in the field of ancient DNA research,
made the first contribution to the understanding of our
genetic relationship to Neandertals when he sequenced
Neandertal mitochondrial DNA in 1997. Together with the
company 454 Life Sciences, Pääbo has now announced a
new milestone in Neandertal research. The two groups
have sequenced a total of more than 3 billion bases of
Neandertal DNA, generating a first draft sequence of
the entire Neandertal genome. Altogether, these
fragments make up more than 60% of the entire
Neandertal genome. These DNA sequences can now be
compared to the previously sequenced human and
chimpanzee genomes in order to arrive at some initial
insights into how the genome of this extinct form
differed from that of modern humans.

In 2006, Pääbo's group published papers together with
454 Life Sciences that showed that it was possible to
use the 454 technology to determine large amounts of
nuclear DNA sequences from late Pleistocene animals
such as mammoths as well as the Neandertal. Building on
these results, Pääbo and Dr. Michael Egholm, Vice
President of Research and Technology of 454 Life
Sciences, a Roche Company, initiated an ambitious
project to sequence the Neandertal genome. Together,
the groups have overcome a number of technical
obstacles in order to arrive at this first view of the
entire genome of an extinct form of human.

One essential element developed by Pääbo's group was
the production of sequencing libraries under "clean-
room" conditions to avoid contamination of experiments
by human DNA. They also designed DNA sequence tags that
carry unique identifiers and are attached to the
ancient DNA molecules in the clean room. This makes it
possible to avoid contamination from other sources of
DNA during the sequencing procedure, which was a
problem in the initial proof-of-principle experiments
in 2006. They also used minute amounts of radioactively
labeled DNA to identify and modify those steps in the
sequencing procedure where losses occur. Together with
other advances implemented during the project, these
innovations drastically reduced the need for precious
fossil material so that less than half a gram of bone
was used to produce the draft sequence of 3 billion
base pairs.

In order to reliably compare the Neandertal DNA
sequences to those of humans and chimpanzees, the
Leipzig group has performed detailed studies of where
chemical damage tends to occur in the ancient DNA and
how it causes errors in the DNA sequences. The
researchers found that such errors occur most
frequently towards the ends of molecules and that the
vast majority of them are due to a particular
modification of one of the bases in the DNA that occurs
over time in fossil remains. They then applied this
knowledge to identify which of the DNA fragments from
the fossils come from the Neandertal genome and which
from microorganisms that have colonized the bones
during the thousands of years they lay buried in the
caves. They have also developed novel and more
sensitive computer algorithms to put the Neandertal DNA
fragments in order and compare them to the human

In total, the group has determined over 100 million DNA
sequence fragments from fossils by the 454 technology
and over a billion DNA sequences with the Solexa
technology, another sequencing technology which is
particularly efficient in reading many short sequences.
The majority of the sequence comes from Neandertal
bones from Vindija Cave in Croatia, which the group
studies as a part of a long-term collaboration between
the Croatian Academy of Sciences and Arts and the
Berlin-Brandenburg Academy.

In order to test if the findings from this Neandertal
are typical of those of other Neandertals, the
researchers have also sequenced several million base
pairs from Neandertals from other sites. Professor
Javier Fortea and colleagues from Oviedo, Spain, have
excavated 43,000-year-old Neandertal bones under
sterile conditions at El Sidron, Spain, that have
yielded DNA sequences, while Dr. Lubov Golovanova and
Dr. Vladimir Doronichev from St. Petersburg, Russia,
have contributed a 60-70,000-year-old bone from
Mezmaiskaya Cave in the Caucasus.

In addition, Dr. Ralf Schmitz from the LVR-Landesmuseum
in Bonn, Germany has allowed a sample to be removed
from the 40,000-year-old Neandertal type specimen,
which was found in 1856 in the Neander Valley, the
source of the name, Neandertal. This will allow crucial
findings from the Croatian Neandertal to be verified in
several Neandertals including the specimen that defines
the Neandertals as a distinct group.

In order to aid in the analysis of the Neandertal
genome, Dr. Pääbo has organized a consortium of
researchers from around the world that plans to publish
their results later this year. They will look at many
genes of special interest in recent human evolution,
such as FOXP2, which is involved in speech and language
in modern humans, as well as genes such as the Tau
locus and the microcephalin-1, implicated in brain
aging and development, respectively. Variants of the
latter genes found among present-day humans have been
suggested to have come from Neandertals. The
preliminary results suggest that Neandertals have
contributed, at most, a very small fraction of the
variation found in contemporary human populations.


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