While next-generation sequencing has allowed researchers to study the genomes of the long-extinct Neanderthals, those approaches have been imprecise because of the low quality of degraded, ancient DNA samples. So, when archaeologists unearthed a finger bone from a human girl in a southern Siberia cave in 2008, scientists could only produce a rough draft of her genome (1). It was enough to learn that she wasn't a modern human or a Neanderthal. She was a member of a new group of humans closely related to the Neanderthals, a group that was dubbed Denisovans after the cave where the sample was found.
"What you have to do is amplify your molecules," explained Meyer. "You have to make many copies so that you can read them out." This is particularly challenging for ancient DNA samples, which are often made up of tiny fragments of single-stranded DNA, rather than long strings of double-stranded DNA that are extracted from living samples. To prepare this single-stranded library for sequencing, Meyer attached short, artificial DNA adaptors to the ends of the fragments to hold them in place during amplification.
Using DNA leftover from the original Denisovans sequencing effort and the new technique, Meyer and colleagues sequenced her genome 31 times over, making the results as complete and precise as the genome of a living person. The results were published online August 30 in Science (2).
"What is particularly fascinating to me is that we're now able to look across the whole genome at all the mutations that have happened since we separated from the Denisovans and their close relatives, the Neanderthals," said lead study author Svante Pääbo, a paleogeneticist at the institute. "We can look at a complete catalog of what's happened in this very last step of human history."
Overall, it’s not a very long list of changes during those last steps. Already, the researchers have determined that some of the changes are in genes related to the wiring of the nervous system, including a couple that have been implicated in autism and one gene that is regulated by FOXP2, which is involved in speech and language as well as synaptic plasticity. Over the next decade, Pääbo’s group and others will continue to analyze the data to see what other functions those genetic changes may have in the body.
By comparing the Denisovan genome to those of modern humans from around the world, the researchers learned that Denisovans contributed genes to modern humans, but to varying extents: they share more genes with people from Papua New Guinea than any other population studied.
In the end, the group found that gene flow from Neanderthals to modern humans was not a single gene flow event from Neanderthals to the ancestors of all non-Africans that was then dispersed throughout the world, a theory that researchers proposed in 2010 based on the first draft of the Denisovan genome. "Something more complicated must have happened," said David Reich, a population geneticist at Harvard University who co-authored the new study. "For example, there may have been at least two Neanderthal gene flow events or a dilution of the initial Neanderthal genetic material in Europe by subsequent expansion of modern humans out of Africa."
The next step for Pääbo's team is to use this new DNA sequencing method on additional fossils to produce a Neanderthal genome of similar quality to that of the Denisovan girl.
- Reich, D., R. E. Green, M. Kircher, J. Krause, N. Patterson, E. Y. Durand, B. Viola, A. W. Briggs, U. Stenzel, et al. 2010. Genetic history of an archaic hominin group from denisova cave in siberia. Nature 468(7327):1053-1060.
- Meyer, M., M. Kircher, M.-T. Gansauge, F. Racimo, K. Prüfer, C. de Filippo, Q. Fu, M. Siebauer, U. Stenzel, et al. 2012 A high-coverage genome sequence from an archaic denisovan individual. Science. [published online August 20, 2012]