Mapping The Neandertal Genome (9/21/2006)

The robust composite skeleton of a Neandertal (left) is unmistakably different from that of a modern human (right) G.J. Sawyer and Blaine Maley

Scientists in Germany and the US are beginning a groundbreaking study to sequence the DNA of Neandertal fossils. The project is to be jointly directed by Svante Paabo, director of the Max Planck Institute for Evolutionary Anthropology and Dr. Michael Eghom, Vice-President of Molecular Biology for 454 Life Sciences.

The project, which intends to sequence the entire 3 billion base pairs that make up the Neandertal genome, hopes to clarify the evolutionary relationship between human and Neandertals. Using the already sequenced human and chimpanzee genomes, the scientists hope to identify those genetic changes that enabled humans to migrate out of Africa and spread around the world.

Collecting, identifying and sequencing the Neandertal DNA is tricky business. When the Neandertal to be studied died, its tissues were invaded by bacteria and fungus, which contaminates the DNA. What isn't contaminated is often destroyed, leaving the remaining DNA in short pieces that have been chemically modified during the fossilization process.

Until recently that was the end of the story, as scientists couldn't rebuild the fragmented DNA, nor could they reconstruct the DNA after the fossilization process. Dr. Paabo has developed techniques for demonstrating the authenticity of sequenced DNA, as well as methods for reassembling fragmented and chemically modified DNA strands.

Over the last 20 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 now combine these methods with high-throughput DNA sequencing.

Dr. Paabo, famous for sequencing the mitochondrial DNA of Neandertals in 1997, has been honing his techniques on several different types of ancient remains including cave bears and woolly mammoths. In all Dr. Paabo's prior cases though, the research was conducted on mitochondrial DNA (mtDNA), which only consists of approximately 0.001% of a mammal's entire genome. The process involves retrieving the mtDNA using polymerase chain reaction (PCR), which requires a large amount of the subjects remains to gather enough DNA to stitch back together. In order to sequence the entire Neandertal genome, scientists would require several kilograms of bones, which are scarce as it is.

This is where 454 Life Sciences comes in. They recently developed a new genome sequencing device called the Genome Sequencer 20. This new technology can amplify a quarter of a million single DNA strands in about four hours. Over the next 2 years, the researchers will sequence 60 billion bases from the Neandertal fossils. They will then take these bases to reconstruct the 3 billion base pairs in the Neandertal genome.

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