454 Life Sciences and Max Planck to Sequence Neandertal Genome
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454 Life Sciences Corporation, a majority-owned subsidiary of CuraGen Corporation, in collaboration with scientists at the Max Planck Institute for Evolutionary Anthropology, has announced in Leipzig, Germany the launch of a project to sequence the complete Neandertal genome.
The project is estimated to take two years and is made possible by 454 Sequencing™ technology and a grant from the Max Planck Society.
"The Max Planck Institute and 454 Life Sciences are working together to sequence the Neandertal genome," explained Svante Paabo, Ph.D., Director of the Department of Evolutionary Anthropology at the Max Planck Institute.
"Our expertise with ancient DNA and the Neandertal, coupled with 454 Sequencing, a next generation sequencing technology with unparalleled throughput, makes this an ideal collaboration."
"The advent of 454 Sequencing has enabled us to move forward with a project that was previously thought to be impossible."
Neandertal inhabited Europe and the Near East until about 30,000 years ago then disappeared after his successor, Homo sapiens, migrated to Europe.
This year marks the 150th anniversary of the discovery of the first Neandertal fossil in Germany's Neander Valley near Dusseldorf.
Dr. Paabo sequenced DNA from a Neandertal fossil in 1997 while at the University of Munich.
"We are excited to collaborate with the Max Planck Institute to sequence the Neandertal genome, as it promises to yield more insight into human biology than the sequencing of any individual human," said Christopher McLeod, President and CEO of 454 Life Sciences.
"This ambitious project is further validation of 454 Sequencing technology and demonstrates that we can sequence any genome, even one from highly degraded samples."
Extracting, identifying and sequencing ancient DNA from fossils is a technically challenging task.
When an organism dies, its tissues are overrun by bacteria and fungi. Much of the DNA is simply destroyed, and the small amount remaining is broken into short pieces and chemically modified during the long period of fossil formation.
This means that when scientists mine tiny samples of ancient bones for DNA, much of the DNA obtained is actually from contaminants such as bacteria, fungi and even scientists who have previously handled the bones.
Over the last twenty years, Dr. Paabo's research group has developed methods for demonstrating the authenticity of ancient DNA results, as well as technical solutions to the problems of working with short, chemically-modified DNA fragments.
Together with 454 Life Sciences, they will now combine these methods with high-throughput DNA sequencing.
"Unlike the human genome project, Neandertal samples are extremely scarce and have been contaminated with microbial DNA over tens of thousands of years. Therefore, this project is only possible with 454 Sequencing technology," said Michael Egholm, Ph.D., Vice President, Molecular Biology, 454 Life Sciences.
Due to such sample contamination, the task of sequencing the Neandertal genome is much more extensive than the task of sequencing the human genome.
454 Life Sciences' Genome Sequencer 20 System is designed to make such an endeavor feasible by allowing approximately a quarter of a million single DNA strands from small amounts of bone to be sequenced in only about five hours by a single machine.
The DNA sequences determined by the Genome Sequencer 20 System are 100-200 base pairs in length, which coincides neatly with the length of ancient DNA fragments.
Over the next two years, the Neandertal sequencing team will reconstruct a draft of the 3 billion bases that made up the genome of Neandertals.
For their work, they will use samples from several Neandertal individuals, including the type of specimen found in 1856 in Neander Valley and a particularly well-preserved Neandertal from Croatia.
The Max Planck Society's decision to fund the project is based on an analysis of approximately one million base pairs of nuclear Neandertal DNA from a 45,000-year-old Croatian fossil, sequenced by 454 Life Sciences.
The Neandertal is thought to have been reasonably sophisticated, forming crews and burying its dead; however, Neandertal is believed to have lacked the higher reasoning function of modern day humans.
Approximately 99% of the Homo sapiens genome is identical to the chimpanzee genome, our closest living relative.
It is estimated that the Neandertal shares 96% of the 1% difference with Homo sapiens. The Neandertal shares the remaining 4% of the difference with the chimpanzee.
"The analysis of the estimated 4% of genome variation that Neandertal shares with the chimpanzee will help us to understand the evolution of characteristics specific to the Homo sapiens and perhaps even aspects of cognitive function," added Dr. Paabo.
"This next leap in Neandertal research will also identify those genetic changes that enabled modern humans to leave Africa and rapidly spread around the world."
"When I conceived the 454 Sequencing technology, I envisioned sequencing personal genomes to help with personal medical care," said Jonathan Rothberg, founder and Chairman of 454 Life Sciences.
"It is wonderful to be on the road toward that goal and sequencing of the Neandertal will certainly be a major milestone, both for the insight it gives us into the origins of Homo sapiens as a species, as well as into what makes humans special."