Genomic secrets of the dead: high-coverage Denisovan sequence

This new technique may make it easier to obtain sequences of long dead individuals whose burial sites are known.

Science: A High-Coverage Genome Sequence from an Archaic Denisovan Individual 

We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30X) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity, indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of “missing evolution” in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.

Science News and Analysis: ... As the international team reports in a paper published online in Science this week, more than 99% of the nucleotides are sequenced at least 10 times, so researchers have as sharp a picture of this ancient genome as of a living person's. “No one thought we would have an archaic human genome of such quality,” Meyer says. “Everyone was shocked by the counts. That includes me.” 

That precision allows the team to compare the nuclear genome of this girl, who lived in Siberia's Denisova Cave more than 50,000 years ago, directly to the genomes of living people, producing a “near-complete” catalog of the small number of genetic changes that make us different from the Denisovans, who were close relatives of Neandertals. “This is the genetic recipe for being a modern human,” says team leader Svante Pääbo, a paleogeneticist at the institute. 

Ironically, this high-resolution genome means that the Denisovans, who are represented in the fossil record by only one tiny finger bone and two teeth, are much better known genetically than any other ancient human—including Neandertals, of which there are hundreds of specimens. The genome offers a glimpse of what the Denisovan girl looked like—her eyes, hair, and skin were brown—and new details about how her lineage evolved. The team confirms that the Denisovans interbred with the ancestors of some living humans and found that Denisovans had little genetic diversity, suggesting that their small population waned further as populations of modern humans expanded. 

... By binding special molecules to the ends of a single strand, the ancient DNA was held in place while enzymes copied its sequence. The result was a sixfold to 22-fold increase in the amount of Denisovan DNA sequenced from a meager 10-milligram sample from the girl's finger. The team was able to cover 99.9% of the mappable nucleotide positions in the genome at least once, and more than 92% of the sites at least 20 times, which is considered a benchmark for identifying sites reliably. 

... Most exciting to Pääbo is the “nearly complete catalog” of differences in genes between the groups. This includes 111,812 single nucleotides that changed in modern humans in the past 100,000 years or so.