Denisova 11: First Known Hybrid Hominin

At first sight, Denny’s remarkable ancestry suggests that Neanderthals and Denisovans must have mated with each other regularly. But Douka counsels caution. “The DNA of Neanderthals and Denisovans are distinct. We can easily tell them apart. That argues against frequent interbreeding. Otherwise they would have ended up with the same DNA.”

Past studies have provided clear evidence that Denisovans and modern humans interbred, and also that Neanderthals and modern humans mated with each. Now, thanks to ZooMs – which has since been used to pinpoint other ancient human remains – there is dramatic evidence of Denisovan and Neanderthal intermingling. But why at Denisova?

One suggestion is that the cave represents a border outpost for both species, one that was situated at the very eastern edge of the range of the Neanderthals, who were primarily a European species, and at the very western tip of the homelands of the Denisovans, who were an eastern species. Occasionally members from both groups would have reached the cave at the same time – with amorous consequences.





It is an idea borne out by detailed studies of Denny’s Neanderthal mother. Her genes show a particularly close affinity with Neanderthals who lived in Croatia, suggesting that the immediate predecessors of Denny’s mother may have been part of a group who slowly migrated east from Europe towards Denisova – where she encountered Denny’s father at the outer edges of each other’s homelands.

It is an intriguing picture, though much more information is required to confirm it. Scientists have no direct evidence that the Denisovans’ homeland range was primarily to the east of the cave, although the fact that their genes have been detected in the DNA of populations in Australia, New Guinea and other parts of Oceania, provides support for this idea and suggests future searches for sites should be focused on eastern Russia, China and south-east Asia.



A great deal more needs to be learned about the Denisovans, says Higham: “What was their distribution? What is the earliest evidence for their emergence from the common ancestor they shared with Neanderthals 500,000 years ago? If we could get a bone or two from other sites, that would be tremendously helpful.” One possible source of fossils could include remains of ancient humans that were placed in museums in Asia decades ago. These could be wrongly labelled, and could be Denisovans, researchers suggest. Unfortunately, it has proved difficult to get hold of these specimens for sampling.

For their part, Douka and Higham are planning on a number of approaches. One of these will be to collaborate with researchers in Chinese laboratories, teaching them how to use ZooMs, and how to use the technology to uncover more Denisovan sites. ZooMs is going to be crucial to this project,” says Douka. “We have shown that it is a powerful tool for pinpointing human fossils. That makes it ideal for tracking down Denisovans.”

Fig. 3: Distribution of Neanderthal-like and Denisovan-like alleles across the Denisova 11 genome.

We conclude that Denisova 11 did not originate from a population carrying equal proportions of Neanderthal and Denisovan ancestry. Rather, she was the offspring of a Neanderthal mother, who contributed her mtDNA, and a Denisovan father.We next plotted the distribution of sites across the genome, for which Denisova 11 carries an allele matching the Altai Neanderthal genome and a different allele matching the Denisova 3 genome. Such sites are distributed largely uniformly (Fig. 3), as would be expected for an F1 offspring of Neanderthal and Denisovan parents. To explore the ancestry of the parents of Denisova 11, we looked for regions in the genome that deviate from a pattern consistent with Denisova 11 being an F1 offspring (Extended Data Fig. 3). Using four tests for enrichment of Denisovan or Neanderthal ancestry, we identify at least five approximately 1-Mb long (0.72–0.95 Mb) regions, all of which are homozygous for Neanderthal ancestry. 

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Fig. 4: Relationships and gene flow events between Neanderthal and Denisovan populations inferred from genome sequences.

This suggests that the Denisovan father of Denisova 11 had some Neanderthal ancestry. Given conservative estimates of the size and number of these regions, it is likely that there was more than one Neanderthal ancestor in his genealogy, possibly as far back as 300–600 generations before his life-time (Supplementary Information 7). Notably, the heterozygosity in the regions of Neanderthal ancestry in Denisova 11 is higher than in the same regions in the genomes of Vindija 33.19 or the Altai Neanderthal, suggesting that the Neanderthals that contributed to the ancestry of Denisova 11’s father were from a different population than her mother (Supplementary Information 5).To explore how the mother of Denisova 11 was related to the two Neanderthals that have been sequenced to high coverage to date, we evaluated the proportions of fragments from Denisova 11 that match derived alleles from either of these two Neanderthal genomes. Denisova 11 shares derived alleles seen in the Altai Neanderthal genome in 12.4% of cases and those present in the Vindija 33.19 genome in 19.6% of cases, showing that the Neanderthal mother of Denisova 11 came from a population that was more closely related to Vindija 33.19 than to the Altai Neanderthal (Supplementary Information 8). We estimate the population split times of Denisova 11’s Neanderthal mother from the ancestors of the Altai Neanderthal to approximately 20,000 years (20 kyr) before the time when the Altai Neanderthal lived, and her split time from the ancestors of Vindija 33.19 to around 40 kyr before Vindija 33.19. 

The population split between the Denisovan father of Denisova 11 and Denisova 3 is estimated to approximately 7kyr before the latter individual (Supplementary Information 8). In Fig. 4, we pres-ent a population scenario that is compatible with these observations as well as with the population split times and molecular estimates of the ages of the three high-coverage archaic genomes2. We caution that the age estimates are associated with uncertainties, for example, regarding demography, mutation rates and generation times, and note that addi-tional gene flow events are likely to have affected the population split times. Nevertheless, that a Neanderthal in Siberia who lived approxi-mately 90 ka shared more alleles with Neanderthals who lived at least 20kyr later in Europe2,7 than with an earlier Neanderthal from the same cave8 suggests that eastern Neanderthals spread into Western Europe sometime after 90 ka or that western Neanderthals spread to Siberia before that time and partially replaced the local population. These two non-mutually exclusive hypotheses could be tested by sequencing the genomes of early Neanderthals from Western Europe.

Nature. 2018 Sep;561(7721):113-116.