Trails for Characterizing Human Predecessors

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 researchers from the U.S. Department of Energy (DOE) Joint Genome Institute (JGI). This study, reported 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, scientists have been stymied in attempts to sequence genomes of extinct species. The DOE JGI researchers overcame a number of of the difficulties normally linked to recovery of DNA from ancient samples. DNA starts degrading at death, while microbes attack the decaying carcass to utilize the nutrients present in the dead organism as an energy source. What remains and confounds the efforts to sequence and characterize these artifacts is an overabundance of microbial contaminants along with the occasional DNA fingerprints contributed unwittingly by the modern fossil hunters or lab workers.

"Among the limitations of prior 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. 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, there was a range of genomic sequence types, including fragments of 21 genes, identified by comparing the cave bear sample to the complete dog genome sequence that exists in the public databases. Dogs and bears, which diverged some 50 million years ago, are 92 percent similar on the sequence level.


Posted by: William    Source