MESSAGE
| DATE | 2005-06-10 |
| FROM | Ruben Safir
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| SUBJECT | Subject: [NYLXS - HANGOUT] Gnenome Reserch
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oint Genome Institute Sequences DNA Of Prehistoric Cave Bears
WALNUT CREEK, Calif. -- The genomic DNA sequencing of an extinct
Pleistocene cave bear species -- the kind of stuff once reserved for
science fiction -- has been logged into scientific literature thanks to
investigators from the U.S. Department of Energy (DOE) Joint Genome
Institute (JGI). The study, published in the June 2 online edition of
the journal Science, has set the research community's sights on
traveling back in time through the vehicle of DNA sequencing to reveal
the story of other extinct species -- including our nearest relatives,
the Neandertals.
Until now, researchers have been stymied in attempting to sequence
genomes of extinct species. The DOE JGI scientists overcame many of the
difficulties normally associated with recovery of DNA from ancient
samples. DNA starts degrading at death when microbes attack the decaying
carcass to utilize the nutrients present in the dead organism as an
energy source. What remains -- and confounds efforts to sequence and
characterize these artifacts -- is an overabundance of microbial
contaminants, along with the occasional DNA fingerprints contributed
unwittingly by modern fossil hunters or lab workers.
"Among the limitations of previous ancient DNA studies was that they
were restricted to mitochondrial DNA sequences," said Eddy Rubin, DOE
JGI director, in whose laboratory the work was conducted. "While
mitochondria are great for learning about evolutionary relationships
between species, to understand the functional differences between
extinct and modern species we really need genomic DNA, and nobody has
been able to purify and sequence large quantities of DNA from these old
samples.
"We applied the standard techniques that we normally use for modern
genome projects to ancient DNA specimens -- a brute-force,
high-throughput sequencing approach," Rubin said. "With this strategy,
we weren't terribly concerned that much of what we were sequencing were
microbial contaminants, but hoped that among the large amounts of
sequence that we were generating would be some of the ancient DNA we
really were interested in.
"We were looking for the proverbial needle in the haystack," Rubin said.
"It worked -- among the expected lion's share of contaminants we
recovered reasonable amounts of 40,000-year-old cave bear DNA and useful
information from it. We were lucky in that we had a very powerful
magnet, in the form of industrial-strength computing, to tease out the
interesting data from a hodgepodge of different DNAs."
It turned out that about 6 percent of the sequence from the sample
yielded cave bear sequence; the rest represented a mosaic of microbial
contaminants. Nevertheless, within that fraction was a range of genomic
sequence types, including fragments of 21 genes identified by comparing
the cave bear samples to the complete dog genome sequence that exists in
public databases. Dogs and bears, which diverged some 50 million years
ago, are 92 percent similar on the sequence level.
The samples of cave bear bones and teeth from the study were collected
from two cave locations in Austria. Extinct for more than 10,000 years,
these particular cave bears, Ursus spelaeus, whose remains are found in
abundance, were related to the ancestors of modern brown bears and polar
bears. Fossil and cave-painting evidence shows that ancient humans
interacted with the cave bears.
"When people hear about our success, they immediately think about how
this strategy could work for dinosaurs," Rubin said. But barring some
fundamental misunderstanding about the nature of DNA decay, he says it
is highly unlikely that viable DNA will be recovered from 150- to
200-million-year-old Jurassic age samples.
Currently, the theoretical age limit is about 100,000 years for samples
preserved in the same conditions that the cave bear specimens were found
-- relatively dry, high altitude, with moderate temperatures -- perhaps
longer if frozen.
"We picked cave bear as an initial test-case ancient DNA target because
the samples we used in the study are roughly the same age as
Neandertals," Rubin said. "Our real interest is in hominids, which
include humans and the extinct Neandertal -- the only other hominid
species that we have to compare with humans.
"Our nearest living relative is the chimp, and that's five million years
of divergence," he said. "Although we are very similar on a sequence
level, there are obvious phenotypic differences. Next, we would like to
access and evaluate genomic information about other hominid species,
Neandertals in particular, as they represent probably our closest
prehistoric relative."
Another possibility is to apply the techniques to the remains found
recently in Indonesia of the Flores Man, nicknamed "the Hobbit."
Although younger, at 18,000 years old, the skeletons were found in a
tropical environment that may have accelerated the DNA degradation
process. The Flores Man is believed to have derived from a more ancient
hominid lineage, Homo erectus, which diverged from modern humans some
two million years ago -- as compared to Neandertal, which diverged
500,000 years ago.
The approach would be to optimize the protocols that succeeded in the
cave bear project to extract useful quantities of DNA from Neandertal
and Flores Man, so that two hominid species could be compared to humans.
Then, by including chimps in that comparison, Rubin said, researchers
would gain insight into the genomic changes between chimps and hominids
and help describe the chain of evolutionary events that led to humans.
"This research represents the merging of two previously unrelated fields
-- ancient species investigations and powerful high-throughput DNA
sequencing technology, DOE JGI's forte," said Dr. Aristides Patrinos,
DOE's associate director of science for Biological and Environmental
Research, whose office supported the published work. "This is yet
another of the many advances enabled by the original investment made by
DOE in the Human Genome Project."
First author on the Science paper was Lawrence Berkeley National
Laboratory postdoctoral fellow James Noonan, who joined DOE JGI's Chris
Detter and Doug Smith, and collaborators at the Max Planck Institute for
Evolutionary Anthropology, Leipzig, Germany and the Institute of
Paleontology, University of Vienna, Vienna, Austria.
The DOE Joint Genome Institute, supported primarily by the Office of
Biological and Environmental Research in the DOE Office of Science, is
among the world leaders in whole-genome sequencing projects devoted to
microbes and microbial communities, model system vertebrates, aquatic
organisms, and plants. Established in 1997, JGI now unites the expertise
of four national laboratories -- Lawrence Livermore, Lawrence Berkeley,
Los Alamos, and Oak Ridge -- along with the Stanford Human Genome Center
to advance the frontiers of genome sequencing and related biology.
Additional information can be found at the JGI Website.
Founded in 1952, Lawrence Livermore National Laboratory has a mission to
ensure national security and to apply science and technology to the
important issues of our time. Lawrence Livermore National Laboratory is
managed by the University of California for the U.S. Department of
Energy's National Nuclear Security Administration.
Editor's Note: The original news release can be found here.
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