The degraded DNA of ancient cave bears
has been sequenced, despite the fact that many considered the
genetic information unrecoverable. The achievement leads researchers
to think they might be able to perform the same trick with DNA from
ancient human relatives, such as the Neanderthals.
In the past,
scientists have managed to retrieve genetic material for analysis
from animals or humans that died in icy or desert environments,
because these allow for good preservation. But the remains of
animals and humans are mostly found in caves, and are heavily
decomposed. The DNA from such specimens is usually mixed up with DNA
from soil microbes and later cave inhabitants, making it difficult
to sequence.
The standard practice for sequencing genes involves making
numerous copies of the initial sample through a process called a
polymerase chain reaction, or PCR. Subjecting ancient DNA to this
does not produce good results because PCR picks up and duplicates
the sequences of modern animals more efficiently. This means that
bits of contaminating DNA often drown out samples from the
prehistoric animal.
"The prevailing idea was that this was
impossible," says James Noonan of the Lawrence Berkeley National
Laboratory in California, who is lead author of the paper that
appears in Science this week1.
Keeping it
simple
To overcome this challenge, Noonan and his colleagues
decided to skip the replicating step and directly sequence the tiny
amount of DNA extracted from two Austrian cave-bear bones that are
more than 40,000 years old. To make sure each portion of DNA was
really from the bears rather than a contaminating source, they
compared each sequence produced with the genome of the dog, a modern
relative of the bear.
The technologies needed to examine such
tiny amounts of DNA directly, along with the reference genome from
the dog, have become available to scientists only
recently.
The team determined that nearly 6% of the sequences
analysed from one of their animal samples belonged to ancient bear:
an unexpectedly large amount. The rest of the DNA probably came from
soil microbes or the palaeontologists handling the bones, the team
says.
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"I
think that this really is a convincing proof of the approach," says
geneticist Edward Rubin, also of the Lawrence Berkeley lab, who
oversaw the investigation. He says the same technique should work on
Neanderthal samples of about the same age or younger.
But
challenges remain. Most important, it will be much harder to weed
out contaminating DNA from the people who excavated the Neanderthal
samples, as both sets of DNA will come from humans. "This is a
problem," admits Noonan.
There were no such worries for the
published study. "We have a strict policy of not employing bears at
our sequencing facility," jokes Rubin.
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