Prehistoric Mating

Munich-based ancient-DNA pioneer Svante Pääbo and his colleagues, described DNA extracted from the bones of the first ever Neanderthal to be discovered, the historic 'Feldhofer' Neanderthal, found in Germany in 1856. That benchmark study was published in the journal Cell in 1997. ³

Svante Pääbo, a palaeogeneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, began his Neanderthal Genome Project about two years ago [that is, 2004]. He and his team have probed 60 Neanderthal specimens from museums for hints that the DNA might have survived millennia of degradation. ⁴

In the summer of 2008, Russian researchers dug up a sliver of human finger bone from an isolated Siberian cave. The team stored it away for later testing, assuming that the nondescript fragment came from one of the Neanderthals who left a welter of tools in the cave between 30,000 and 48,000 years ago. Nothing about the bone shard seemed extraordinary.

Its genetic material told another story. When German researchers extracted and sequenced DNA from the fossil, they found that it did not match that of Neanderthals — or of modern humans, which were also living nearby at the time. The genetic data, published online in Nature, reveal that the bone may belong to a previously unrecognized, extinct human species that migrated out of Africa long before our known relatives.

"This really surpassed our hopes," says Svante Pääbo, senior author on the international study and director of evolutionary genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. "I almost could not believe it. It sounded too fantastic to be true." ⁵

Although a Neanderthal mtDNA genome differs from that of Homo sapiens at 202 nucleotide positions on average, the Denisova Cave sample differed at an average of 385 positions.

The differences imply that the Siberian ancestor branched off from the human family tree a million years ago, well before the split between modern humans and Neanderthals. If so, the proposed species must have left Africa in a previously unknown migration, between that of Homo erectus 1.9 million years ago and that of the Neanderthal ancestor Homo heidelbergensis, 300,000 to 500,000 years ago. ⁶

Skeletal puzzle
Archaeologists are usually pretty good at distinguishing between the bones of ancient humans and those of other animals. But tiny, crumbled fragments with no clear features pose a challenge.

These fragments often make up a significant portion of the remains recovered from archaeological sites, says Tom Higham, an archaeologist at the University of Oxford, UK.

At Denisova Cave, for example, most bone material has been broken up over time by animals such as hyenas, rendering identification by eye impossible. “So it just basically sits in storage not doing anything,” he says,.

But even these tiny bone fragments contain tell-tale molecular signals that can be used to identify which animal group they belong to.

Using a technique called zooarchaeology by mass spectrometry, or ZooMS, researchers can extract collagen — a tough, fibrous protein that forms connective tissue — from a bone and break it down into its constituent units, called peptides. They then look for characteristic ‘fingerprints’ that differentiate the peptides of a hominin from those of, for example, a bear or mammoth.

Denny’s bone fragment was the first to be classified as hominin using this technique, described in a 2016 paper before her DNA had been extracted and sequenced.

The team has examined hundreds more bones since then, identifying the four further hominin specimens which they are currently analysing. ⁷

The denizens of Denisova also bred with contemporary humans, according to Pääbo and Reich's analysis. But the only traces of their DNA to be found in modern humans were in residents of Melanesia, thousands of miles away from Denisova, suggesting that the Denisovans had once lived across Asia. In 2008, Pääbo's team set up a lab in Beijing to screen fossils that might contain Denisovan DNA, in the hope of learning more about them and their interactions with modern humans. Currently, the bone that yielded the Denisovan genome, and a single molar from the same cave, are their only known fossil remains, but other archaic human fossils from Asia could bear traces of this group. ⁸

Abstract
Neanderthals and Denisovans are extinct groups of hominins that separated from each other more than 390,000 years ago. Here we present the genome of ‘Denisova 11’, a bone fragment from Denisova Cave (Russia) and show that it comes from an individual who had a Neanderthal mother and a Denisovan father. The father, whose genome bears traces of Neanderthal ancestry, came from a population related to a later Denisovan found in the cave. The mother came from a population more closely related to Neanderthals who lived later in Europe than to an earlier Neanderthal found in Denisova Cave, suggesting that migrations of Neanderthals between eastern and western Eurasia occurred sometime after 120,000 years ago. The finding of a first-generation Neanderthal–Denisovan offspring among the small number of archaic specimens sequenced to date suggests that mixing between Late Pleistocene hominin groups was common when they met.

Main
Neanderthals and Denisovans inhabited Eurasia until they were replaced by modern humans around 40,000 years ago (40 ka). Neanderthal remains have been found in western Eurasia, whereas physical remains of Denisovans have thus far been found only in Denisova Cave, where Neanderthal remains have also been recovered. Although little is known about the morphology of Denisovans, their molars lack the derived traits that are typical of Neanderthals.

DNA recovered from individuals of both groups suggests that they diverged from each other more than 390 ka. The presence of small amounts of Neanderthal DNA in the genome of ‘Denisova 3’, the first Denisovan individual to be identified, indicates that the two groups mixed with each other at least once. It has also been shown that Neanderthals mixed with the ancestors of present-day non-Africans around 60 ka, and possibly with earlier ancestors of modern humans; and that Denisovans mixed with the ancestors of present-day Oceanians and Asians. Denisovans may furthermore have received gene flow from an archaic hominin that diverged more than a million years ago from the ancestors of modern humans. ⁹