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As 454 Enabled Mammoth Project, Next-Generation Sequencers Will Drive Paleogenomics

NEW YORK, Jan. 3 (GenomeWeb News) - As next-generation sequencing technologies emerge on the market, some experts believe they will be used for projects other than medical sequencing. This notion was reinforced two weeks ago when scientists announced the first genome sequences from a wooly mammoth, which became extinct about 10,000 years ago.


Now some scientists say this project could signal the start of a sequencing trend in paleogenomics --- as well as a potential new market for emerging sequencing technologies, which enabled the wooly mammoth research, published in the Dec. 22 issue of Science.


"The academic interest of being able to go back in time and recover potentially fairly complete genomic sequences for these ice age mammals is huge," said Ross MacPhee, curator of vertebrate zoology at the AmericanMuseumof Natural History, who was involved with the mammoth project. "Although there are theories as to why all the big guys disappeared ... the one big part of the puzzle that we were missing up until now is very much sense as to what happened to them at a genetic level." 


The wooly mammoth was sequenced using 454 Life Sciences' Genome Sequencer 20. PennState, which owns an instrument, collaborated with seven other partners to complete the project, including McMasterUniversityin Canadaand research institutions in Russia, the United Kingdom, France, and Germany.


Stephan Schuster, an associate professor at PennState, said they wouldn't have been able to do the project without the high throughput instrument.


"When you are dealing with ancient DNA, there are a couple of considerations," Chris McLeod, chief operating officer and president of 454, told GenomeWeb News last week. "One is there is a lot of bacterial contamination, so typically you have to sequence an awful lot of bacteria in order to get your target," he said. Of the 28 million base pairs sequenced from the wooly mammoth sample, a little less than half, or around 13 million, actually belonged to the mammoth.


Ancient DNA is also highly fragmented, making it a nice fit for 454's read length, which runs around 100 bases.


The other key to the project was the ability to sequence the ancient DNA more directly than if one were using a conventional Sanger instrument. The Genome Sequencer 20 compartmentalizes single DNA molecules prior to the amplification step in a lipid vesicle. "This way we avoid any amplification bias that occurs in pools of DNA," Schuster said.


MacPhee said that through his museum's collaboration with Penn, musk ox and wooly rhinoceros may be next in line for sequencing. He said he believes most ancient DNA sequencing will be done through collaborations between institutions that own a sequencer and those with expertise in ancient DNA. Leaders in ancient DNA research include the Universityof Adelaidein Australia, Lawrence Berkeley National Laboratory, Stanford University, Max Planck Institute for Evolutionary Anthropology, University College of London, and OxfordUniversity. "These are the ones that are leaders in the general field of ancient DNA, have the talent, and would be expected to get on this paleogenomics high horse," MacPhee said.


Some have already started. Eddy Rubin, director of the Genomics Division at Lawrence Berkeley National Laboratory and director of the Joint Genome Institute --- the latter of which has had a 454 instrument since June --- said he has started using 454's instrument to "sequence several ancient samples." He declined to elaborate.


Kate O'Rourke covers the next-generation genome-sequencing market for GenomeWeb News. E-mail her at [email protected].

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