More Genomes From Denisova Cave Show Mixing of Early Human Groups
COLD SPRING HARBOR, NEW YORK—In starts with single, rather than double, strands 2010, a girl’s pinkie bone from Denisova Cave of DNA. The approach provided a startlingly in Siberia added a new branch to the human detailed view of the Denisovan pinkie bone family tree. The bone was so well preserved (Science, 31 August 2012, p. 1028). that researchers could fully sequence its But this powerful technique had yet to be genome and glimpse the DNA of archaic peo- applied to Neandertals. So Pääbo was thrilled ple now called Denisovans (Science, 28 Janu- when the DNA in the sample taken from the ary 2011, p. 392; 26 August 2011, p. 1084). toe bone proved to be 60% Neandertal. The Now, researchers have analyzed three more researchers were able to sequence each base samples from that same cave using a power- 50 times over, on average—enough coverful new method that reveals ancient genomes age to ensure the sequence is correct. This in brilliant detail. One sample, a Neander- approach also provided low coverage of the tal toe bone, has yielded a nearly complete, genome from another fossil, a Neandertal high-coverage genome of our closest cousins, baby’s rib, more than 50,000 years old, from a paleogeneticist Svante Pääbo from the Max cave in Russia’s Caucasus region between the Planck Institute for Evolutionary Anthropol- Caspian and Black seas. ogy in Leipzig, Germany, reported at a meetIn a 10 p.m. talk to a full house, Pääbo ing here last week.* The analyses paint a complex picture of mingling among ancient human groups, Pääbo reported. The data suggest inbreeding in Neandertals, a large Denisovan population, and mixing between Denisovans and an even earlier mystery species. “It’s wonderful; amazing,” says Eric Lander, director of the Broad Institute in Cambridge, Massachusetts. “It opens up a vista on the past world.” Neandertals, the closest known relatives to modern humans, ranged A cave for all people. Denisova Cave in across Europe to western Asia Siberia yielded a Neandertal toe bone (inset) as from perhaps 300,000 years ago well as fossils of a new group of humans called until about 30,000 years ago. Their the Denisovans. overlap in time and space with our ancestors had fueled debate about whether offered some surprising results from the toe the two species had interbred. Then, in 2010, bone. For long stretches, the DNA from each Pääbo’s group published a low-coverage parental chromosome is closely matched, sequence (1.3 copies on average) of DNA strongly suggesting that this Neandertal was from three Neandertal bones from Croatia, the offspring of two first cousins, he said. which showed interbreeding: About 2% of Comparing the data with those from the fosthe DNA in living people from outside Africa sils from Croatia and the Caucasus showed originally comes from Neandertals (Science, that these populations were fairly separated 7 May 2010, pp. 680 and 710). from one another. The group also compared That first Neandertal sequence was a huge the chunks of Neandertal DNA found in livaccomplishment, as Neandertal DNA made ing people with each of these three Neanup just a few percent of the DNA in the fos- dertal samples. The closest match was with sils, the rest being bacterial and other con- the Caucasus population, suggesting that taminants. Since then, the Leipzig group has interbreeding with our ancestors most likely found ways to zero in on human genetic mate- occurred closer to that region. rial and to get more from degraded ancient From the detailed genomes of both NeanDNA by using a sequencing method that dertals and Denisovans, Pääbo and Montgomery Slatkin of the University of California, *The Biology of Genomes, 7 to 11 May. Berkeley, estimated that 17% of the SCIENCE VOL 340


van DNA was from the local Neandertals. And the comparison revealed another surprise: Four percent of the Denisovan genome comes from yet another, more ancient, human— “something unknown,” Pääbo reported. “Getting better coverage and more genomes, you can start to see the networks of interactions in a world long ago,” says David Kingsley, an evolutionary biologist at Stanford University in Palo Alto, California. With all the interbreeding, “it’s more a network than a tree,” points out Carles LaluezaFox, a paleogeneticist from the Institute of Evolutionary Biology in Barcelona, Spain. Pääbo hesitates to call Denisovans a distinct species, and the picture is getting more complicated with each new genome. Pääbo’s team also deciphered additional Denisovan DNA, both nuclear and mitochondrial, from two teeth found in different layers in Denisova Cave. The nuclear DNA confirmed that both teeth are Denisovan. But, surprisingly, one tooth showed more than 80 mitochondrial DNA differences from both the other tooth and the pinkie bone. These Denisovans, who lived in the same cave at different times, were as genetically diverse as two living humans from different continents and more diverse than Neandertals from throughout their range, says Susanna Sawyer from Pääbo’s lab. Such diversity implies that the Denisovans were a relatively large population “that at some point may have outnumbered Neandertals,” Pääbo said. In addition, the genomes are clarifying genetic changes that underlie our own evolution. “We will be able to know all the changes that are ancestral,” Lalueza-Fox says. Pääbo and his colleagues have lined up the chimp, modern human, Neandertal, and Denisovan genomes to see what’s unique to our species. The catalog includes 31,000 single-base changes, which led to 96 protein changes, and more than 3000 changes in regulatory regions, as well as 125 small insertions and deletions, Pääbo reported. Peter Sudmant from the University of Washington, Seattle has already begun scanning the Neandertal genome for uniquely human duplications and deletions. “It’s something we thought we would never be able to do,” he says. Adds Kingsley: “It will take a long time to figure out the real causative events and figure out what traits they control, but it’s a finite list.”

17 MAY 2013


Published by AAAS

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