454 Life Sciences Corporation, a majority owned subsidiary of CuraGen Corporation, in collaboration with scientists at the Max Planck Institute for Evolutionary Anthropology, announced in Leipzig, Germany the launch of a project to sequence the complete Neanderthal genome.

Neanderthal is the closest relative to humans and knowledge of its genetic composition, will significantly enhance the understanding of human biology. 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 Neanderthal genome. Our expertise with ancient DNA and the Neanderthal, coupled with 454 Sequencing, a next generation sequencing technology with unparalleled throughput, makes this an ideal collaboration," said Svante Paabo, PhD, Director of the Department of Evolutionary Anthropology at the Max Planck Institute. "The advent of 454 sequencing has enabled us, to move forward with a project that was previously thought to be impossible."

Neanderthal 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 Neanderthal fossil, in Germany's Neander Valley near Dusseldorf. Dr Paabo was the first to sequence DNA from a Neanderthal fossil in 1997 while at the University of Munich.

"We are excited to collaborate with the Max Planck Institute to sequence the Neanderthal genome, as it promises to yield more insight into human biology, than the sequencing of any individual human," stated 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 which 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, 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. By enabling a method of sequencing, which is more comprehensive and less expensive than conventional sequencing methods, 454 sequencing is well suited for such a project.

"Unlike the human genome project, Neanderthal 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 technologies," said Michael Egholm, PhD, Vice President, Molecular Biology, 454 Life Sciences.

Due to such sample contamination, the task of sequencing the Neanderthal genome is much more extensive than the task of sequencing the human genome. 454 Life Sciences' Genome Sequencer 20 System makes such an endeavour 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 Neanderthal sequencing team will reconstruct a draft of the 3 billion bases that made up the genome of Neanderthals.

The Neanderthal is thought to have been reasonably sophisticated, forming crews and burying its dead; however, Neanderthal is believed to have lacked the higher reasoning function of modern day humans. Approximately 99 per cent of the Homo sapiens genome is identical to the chimpanzee genome, our closest living relative. It is estimated that the Neanderthal shares 96 per cent of the 1 per cent difference with Homo sapiens. The Neanderthal shares the remaining 4 per cent of the difference with the chimpanzee.

"The analysis of the estimated 4 per cent f genome variation that Neanderthal shares with the chimpanzee, will help 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 Neanderthal 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. It is wonderful to be on the road toward that goal and sequencing of the Neanderthal 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," stated Jonathan Rothberg, founder and Chairman of 454 Life Sciences.