The Denisova genome: An unexpected window into the past

The Denisova genome: An unexpected window into the past

John Hawks

Department of Anthropology University of Wisconsin-Madison 5240 Social Science Building 1180 Observatory Drive Madison, WI 53706



In 2010, scientists from the Max Planck Institute for Evolutionary Anthropology reported a draft genome sequence from ancient skeletal remains from Denisova Cave, in the Altai Mountains of Russia Reich:Denisova:2010. Following the description of the genomes of three Neandertals from Vindija, Croatia, earlier in 2010 Green:draft:2010, the Denisova find represented the second Pleistocene human population from which genome-wide evidence had been recovered. In 2012, a high-coverage genome from one of the Denisova individuals was made available to researchers Meyer:Denisova:2012. This has provided the best evidence yet discovered about the genetics of any Pleistocene-era individual. Still, this exceptional specimen has provoked mystery.

While the Denisova genomes closest similarity is with the Neandertal genomes, it is nearly as genetically different from Neandertals as both genomes are from those of living people. In addition to the nuclear genome, three mitochondrial genomes were sequenced from Denisova skeletal remains, all of which are also substantially different from the mitochondrial genomes of known Neandertal specimens, including Neandertal specimens from nearby sites in the Altai and across Central Asia Krause:2007. The Denisova genetic evidence appears to represent an ancient population substantially different from the Neandertals, adjacent to the easternmost end of the Neandertal range of occupation. Reich and colleagues Reich:Denisova:2010 dubbed this ancient population the “Denisovans”, and turned to consider its relationship with living and ancient populations.

Archaeological associations

The Denisova remains preserve very little anatomical detail, and it is impossible at present to attribute them to any previously-known group of fossil hominins. Most of the genetic evidence comes from a terminal fifth manual phalanx from an adolescent girl. This has no informative anatomy to base anatomical comparisons to other early human specimens. The first reported third molar has length and breadth dimensions within the size range occupied by australopithecines and early Homo, both H. habilis and H. erectus. There are no distinctive morphological characters that would allow it to be assigned to any taxon.

Adding to the mystery, the Denisova finger bone has anomalously good preservation of DNA. The cold temperature within the cave year-round likely contributed to the preservation, but nonetheless it is exceptional compared to other cold-temperature caves. There are no direct dates on the skeletal remains from Denisova. By inference (based on their genetic sequences), the skeletal individuals are likely to be older than the Upper Paleolithic Meyer:Denisova:2012, but the stratigraphy does not require this.

The human remains come from layer 11 within the rear gallery of the cave. The stone artifacts in this layer come from a broad range of industries from Upper Paleolithic to a local Mousterian. The late Mousterian at the site includes a good number of blades, although it is technically different from initial Upper Paleolithic industries in the Altai, including the assemblages from Kara Bom, which exhibit strongly blade-based flaking techniques. It is not clear which of the stone tool industries present in Denisova may have been made by the Denisovan population.

How were the Denisovans related to Neandertals?

The Denisova, Neandertal and human genomes are close to a trichotomy in terms of their average relationship, with the Denisova genome being slightly closer to the Neandertals than to living people Reich:Denisova:2010, Meyer:Denisova:2012. For any particular gene, of course, there may be sister pairings between any two of those three, and in many cases, between Denisovans and some living humans to the exclusion of other living humans. This gives rise to several tricky statistical issues as we consider particular gene loci.

The similarity of Denisova and Neandertal genomes suggests that they emerged from a single population. This possibly was the early Middle Pleistocene population of Eurasia. Green and colleagues Green:draft:2010 derived Neandertals from a common ancestor with living Africans only 250,000-400,000 years ago. A model including the Denisova data, reported by Reich and colleagues Reich:Denisova:2010 puts the emergence of a Neandertal-Denisova clade at between 190,000 and 520,000 years ago, and the divergence of the Neandertal and Denisova branches around 50,000-100,000 years later. This is later than the time of the last unequivocal H. erectus fossils, and more than a half million years after the Trinil individual – type specimen of Homo erectus – lived. Based on this chronology, the Denisova genome does not represent Homo erectus or any hominin population derived from the initial diversification of Homo.

A slower mutation rate might bring the most recent specimens of Homo erectus into the temporal range of the Denisovan population, by elevating the time of divergence of Denisovans, Neandertals and contemporary African peoples. Whole-genome sequencing of human parent-offspring pairs, as well as resequencing of more limited regions of the genome, has suggested a slower rate of substitutions Hawks:2012, Scally:Durbin:2012. This would be consistent with a much earlier diversification of Denisovan and Neandertal genomes, making it possible that they came from an early Middle Pleistocene adaptive radiation.

The Denisovans were too closely related to living humans to represent Homo erectus, as it is currently understood. Homo erectus occurred widely in Asia, including China and Java, and Africa during the span from 1.95 million to 750,000 years ago. In China and Java, fossils attributed to Homo erectus persisted until 200,000 years ago. There is no unequivocal fossil of Homo erectus after 200,000 years ago.

The mtDNA sequence of the Denisova genome is an outgroup to a clade including both humans and Neandertals, and appeared to branch from our ancestors roughly a million years ago. In addition to the finger bone, Reich and colleagues recovered the mtDNA of a second individual from Denisova Cave, represented by an isolated third molar Reich:Denisova:2010. Reich and colleagues Reich:Denisova:2010 showed that the mtDNA divergence between Denisova and the modern-Neandertal clade is deeper than expected given the nuclear genome genealogical divergence. They also showed that the nuclear genomes of Neandertals and Denisovans are somewhat closer than either is to the majority ancestors of living people. They discuss two possible explanations.

One scenario a mixture of the Denisovans with a more ancient Pleistocene population, followed by introgression of a more ancient mtDNA clade into the Denisovans. This would assert an ancient structured population preceding the origin of Denisovans, presumably from one of the Middle Pleistocene populations of Africa or Eurasia. A second scenario is incomplete lineage sorting, in which an earlier mtDNA divergence was captured by the Denisova and Neandertal populations at the time of their divergence and differentially lost from them.

Descendants of Denisovans

Some living humans trace a significant fraction of their ancestry to the population represented by the Denisova genome. As in the case of Neanderthals, different human populations show significantly different levels of similarity to the Denisova sequence. For Neanderthals, the similarities indicated between one and four percent Neanderthal ancestry for living people outside of Africa, including the peoples of Europe, East and South Asia, Australasia and the Americas Green:draft:2010. In the case of the Denisova sequence, the greatest similarities are with living people in Melanesia, as represented by genome samples from Papua New Guinea and Bougainville. The similarities are consistent with approximately 4 percent contribution of a Denisova-like population to the ancestry of these living Melanesians Reich:Denisova:2010. The paper estimates that together, the Denisova and Neanderthal-derived genes account for 8% of the ancestry of these living people.

The most plausible hypothesis to explain Denisovan ancestry of Australians and other Oceanian peoples is that the Denisova Cave individuals represent a much larger and more widespread population. A population of modern humans originating in Africa who were dispersing in the direction of island Southeast Asia may have encountered and mixed with a South or Southeast Asian population of Denisovans. The dispersing population would have absorbed some adaptive genes, which would have increased in frequency thereby increasing the apparent genetic contribution of the indigenous Pleistocene population.

Denisovan demography

It has become possible to make some good estimates of demographic history using only a single diploid genome, using a technique developed by Li and Durbin Li:Durbin:2011. Meyer and colleagues Meyer:Denisova:2012 applied this technique to the Denisova genome, finding that its genetic history contrasts with that of living human populations. Whereas African populations and living humans outside Africa share signs of population growth in the last 100,000 years, the Denisova genome seems to have come from a population that had long been small, and may have been shrinking.

We know that Neandertals of Europe and Central Asia lived in an environment that was relatively marginal for their technology and subsistence pattern. In contrast, the Denisovan population might well have lived in areas far from the Altai, such as South or Southeast Asia. These areas might have been expected to give rise to a larger and more successful human population. Several different hypotheses are possible explanations for the appearance of a Denisovan population restriction. Maybe Denisovans didn’t live in South or Southeast Asia at all, or the Denisova genome itself may be a poor representative of a broader population. The demographic model of Li and Durban does not encompass admixture, just the probability of gene coalescence across time. We have recently begun to appreciate the reality of ancient African population structure. If those initial African populations were more divergent from each other than Neandertals and Denisovans, their later mixture would give rise to a picture of early population expansion, even if each of them had relatively low (Denisovan-like) diversity.

Human similarities and differences from Denisova

The Denisova genome lacks some genetic variations that are otherwise found universally in living human populations Meyer:Denisova:2012. The number of such human-specific changes is relatively small, and they may give rise to a greater understanding of recent evolutionary change in human ancestors.

One interesting genetic detail about humans is our chromosome 2, which is an amalgam of two different chromosomes in the other great apes. Sometime in our evolution, two separate chromosomes fused into one, giving humans a karyotype of 46 chromosomes where chimpanzees, bonobos and gorillas have 48 chromosomes. The high-coverage genome was sufficient to show that Denisova shared the human fusion Meyer:Denisova:2012. It remains unclear whether this fusion made any difference to any phenotype in ancient humans. However, considering that the fusion occurred prior to the divergence of Neandertals and Denisovans, we can conclude that this particular event did not contribute to any postzygotic isolation or chromosomal incompatibility between Neandertals, Denisovans, and modern humans.


The Denisova genome is the first high-coverage genetic evidence from a Pleistocene human population. It has already yielded substantial new evidence about the biology, demography and relationships of these ancient people. Of course, one exciting aspect of the discovery is as a proof of concept for future high-coverage archaic genomes. Recent work by Meyer and colleagues Meyer:Denisova:2012 makes explicit that the Denisova phalanx simply has better endogenous DNA preservation than any other specimen known. That being said, new sequencing methods have greatly increased the sequence yield from the Denisova sample. Such techniques may bring higher coverage into reach for several specimens that are currently only sequenced at very low coverage, including the Vindija, Mezmaiskaya, and El Sidron Neandertals.

It has often been that paleoanthropology uses technological advances in other fields. But with ancient DNA, we really see an organic growth of technology along with research questions about our evolution. In our work on the ancient genomes, we’re making some progress pushing forward knowledge about human biology by understanding human evolution. Evolution really is the fundamental principle of biology, but using evolution to learn about biology sometimes requires traveling through time. Ancient DNA gives paleoanthropologists a time machine to bring new insights into reach.