Ancient DNA puts a face on the mysterious Denisovans, extinct cousins of Neanderthals

Many of us can picture the face of a Neanderthal, with its low forehead, beetled brows, and big nose. But until now, even scientists could only guess at the features of the extinct Denisovans, who once thrived across Asia. For more than 10 years, these close cousins of Neanderthals have been identified only by their DNA in a handful of scrappy fossils.

Now, a new method has given the Denisovans a face. A recently developed way to glean clues about anatomy from ancient genomes enabled researchers to piece together a rough composite of a young girl who lived at Denisova Cave in Siberia in Russia 75,000 years ago. The results suggest a broad-faced species that would have looked distinct from both humans and Neanderthals.

Ludovic Orlando, a molecular archaeologist at the University of Copenhagen who wasn't involved in the work, calls the approach "clever." But he and others caution against making specieswide generalizations based on a single individual.

Perhaps 600,000 years ago, the lineage that led to modern humans split from the one that led to Neanderthals and Denisovans. Then about 400,000 years ago, Denisovans and Neanderthals themselves split into separate branches. Denisovans ranged from Siberia to Southeast Asia and may have persisted until as recently as 30,000 years ago, based on their genetic legacy in living Southeast Asians.

Hundreds of Neanderthal skeletons, including intact skulls, have been found over the years. But the only fossils conclusively linked to Denisovans are a pinkie bone from the girl plus three teeth, all from Denisova Cave, and a recently identified lower jaw from China's Baishiya Karst Cave.

Then in 2014, researchers introduced a novel method based on epigenetics—a set of molecular knobs that can turn gene expression up or down—to analyze gene regulation in long-extinct hominins. One such knob is a chemical modification called methylation, which silences gene expression. In methylated DNA, one nucleotide, cytosine, degrades over thousands of years into a different end product than usual. By tracking that degradation in an ancient genome, scientists can create a methylation "map."

Liran Carmel and David Gokhman, geneticists at the Hebrew University of Jerusalem, and their colleagues applied this method to DNA in the girl's pinkie from Denisova Cave. They compared the girl's methylation map with similar maps of modern humans, Neanderthals, and chimpanzees, focusing on areas where the degree of methylation differed by more than 50%.

To find out how Denisovans' unique methylation patterns might have influenced their physical features, the researchers consulted the Human Phenotype Ontology database of genes known to cause specific anatomical changes in modern humans when they are missing or defective. Because methylated genes are "turned off," they may have effects comparable to those of the genes in the database, making it possible for researchers to infer Denisovan anatomy.

The method can't provide exact body measurements. "We can say [Denisovans had] longer fingers [than modern humans for example], but we cannot say 2 millimeters longer," Carmel explains. In total, the researchers discovered 56 Denisovan anatomical features that may have differed from humans or Neanderthals, 34 of them in the skull. As expected, the Denisovan girl looked fairly similar to a Neanderthal, with a similarly flat cranium, protruding lower jaw, and sloping forehead, the researchers report this week in Cell.

Yet she also had key differences. The reconstructed face was notably wider than that of a modern human or Neanderthal, and the arch of teeth along the jawbone was longer.

A test of the model came while Cell's editors reviewed the paper. Another team concluded based on ancient proteins in the Baishiya jawbone that it belonged to a Denisovan. Carmel and colleagues eagerly matched their model Denisovan to the real thing, and found a close fit: The jawbone was wider than that of either humans or Neanderthals, and there were hints that it protruded about as much as in Neanderthals but more than in modern humans. "It almost perfectly matched our predictions, which was very nice for us," Carmel says. The team's predictions also match skull fragments from Xuchang, China, that some argue belong to a Denisovan, he adds, and the method may help identify additional Denisovan specimens.

Because the current study is based on a single individual and the technique only returns relative measurements, researchers caution that it's an imperfect reflection of what the species looked like. Only more Denisovan fossils can confirm whether this portrait is accurate, says Gabriel Renaud, a bioinformatician at the University of Copenhagen, who adds that he wishes the authors had publicly released their computational methods so that others could replicate the findings.

"If you were to find a single Homo sapiens fossil and it's an NBA basketball player, then you might conclude that Homo sapiens were 7 feet tall," he says. "It's an interesting approach, but we can't verify the predictions until several Denisovan skeletons are found."