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Some things age gracefully—unfortunately, DNA isn't one of them, and researchers hoping to uncover genetic information about long-dead species have been thwarted by degradation that leaves genomic DNA severely fragmented. “Mitochondrial DNA has been recovered successfully from a wide range of samples 50,000 years and older,” explains James Noonan, a postdoctoral fellow working with Edward Rubin at Lawrence Berkeley National Laboratory. “But genomic sequence has been recovered in very small amounts, and that's under special circumstances, where the material's frozen... or else it comes from a very dessicated environment.”

The main problem is that most researchers, recognizing the scarcity of ancient genomic material, have tried to amplify it first—but the DNA is generally far too degraded to amplify. Noonan and Rubin, working with Svante Pääbo's group at the Max Planck Institute, decided on a more direct approach. They began by extracting total DNA from cave bear tooth and bone samples, dated as being more than 40,000 years old. This DNA was enzymatically repaired, and then directly ligated into vector backbones to generate genomic libraries. The researchers benefited from the recent completion of the dog genome sequence—dogs and bears are closely related, with over 90% genomic sequence identity—and used this data as a framework for analysis of their sequence information.

Most of what was cloned came from environmental fungi or microbes, but a considerable amount of sequence was identified that lined up quite well against annotated dog sequence, revealing putative cave bear exons and regulatory sequences. “If we had the will, and the money, and the time, we could sequence the entire genome from these libraries,” says Noonan. This is not the goal, however, and the team sees this study as a trial run for a more ambitious and relevant project. “The cave bear was useful because it's the same age as Neanderthal remains and [has] about the same level of preservation. They come from the same kind of environment,” says Noonan, and after optimization of their techniques, the team will immediately begin work on reconstructing the Neanderthal genome, for direct comparison against humans and chimpanzees. Noonan sees great promise in this approach, and suggests it may even work with far older specimens. “If you look back at the literature in the ancient DNA field, you will find everybody saying that this is impossible, that you will never get significant amounts of genomic DNA from any sample... but you can! And you can do it using methods that you use to sequence modern genomes.”