A analysis workforce led by Max Planck Institute for Evolutionary Anthropology scientists has generated the high-quality genome meeting of a Denisovan utilizing DNA from an historic molar discovered at Denisova Cave. It belonged to a person who lived roughly 200,000 years in the past — greater than twice as way back as the one beforehand sequenced Denisovan particular person. The brand new genome is forcing the researchers to rethink when and the place early human teams met, mingled and migrated throughout Asia.
An artist’s idea of a Penghu Denisovan strolling below the brilliant Solar throughout the Pleistocene of Taiwan. Picture credit score: Cheng-Han Solar.
Dr. Stéphane Peyrégne, an evolutionary geneticist on the Max Planck Institute for Evolutionary Anthropology, and his colleagues recovered the genome of a Denisovan from a molar unearthed at Denisova Cave within the Altai Mountains of southern Siberia — the identical web site the place Denisovans had been first recognized in 2010 by way of DNA evaluation of a finger bone.
The cave has since change into a cornerstone of human evolutionary analysis, revealing repeated occupations by Denisovans, Neanderthals and even the child of parents from both groups.
“Denisovans, an extinct human group, had been first recognized based mostly on historic DNA extracted from Denisova 3, a finger phalanx found at Denisova Cave within the Altai Mountains of Siberia in 2008,” Dr. Peyrégne and co-authors stated.
“Evaluation of the nuclear genome from this particular person revealed that Denisovans had been a sister group to Neanderthals, one other group of now extinct people who lived in Western Eurasia within the center and late Pleistocene.”
“Whereas twelve fragmentary stays and one skull have since been attributed to Denisovans based mostly on DNA or protein evaluation, solely Denisova 3 has yielded a high-quality genome.”
The newly-analyzed tooth belonged to a male Denisovan who lived about 200,000 years in the past, at a time when trendy people had not but left Africa.
“In 2020, an entire left higher molar was present in layer 17, one of many lowest cultural layers of the South Chamber of Denisova Cave, dated to 200,000-170,000 years in the past by optically stimulated luminescence,” the scientists defined.
“Designated as Denisova 25, this molar is comparable in measurement to the opposite molars found at Denisova Cave, Denisova 4 and Denisova 8, and bigger than these of Neanderthals in addition to most different Center Pleistocene and later hominins, suggesting that it doubtlessly belonged to a Denisovan.”
“Two samples of two.7 and eight.9 mg had been eliminated by drilling one gap on the cemento-enamel junction of the tooth, and twelve subsamples, starting from 4.5 to twenty.2 mg, had been obtained by gently scratching the outer layer of one of many roots with a dentistry drill.”
Due to distinctive DNA preservation, the authors had been capable of reconstruct the genome of Denisova 25 at excessive protection, making it comparable in high quality to the genome of the 65,000-year-old Denisova 3 lady.
Denisovans had been in all probability dark-skinned, not like the pale Neandertals. The image exhibits a Neanderthal man. Picture credit score: Mauro Cutrona.
Evaluating the 2 genomes revealed that Denisovans had been removed from a single, secure inhabitants.
As a substitute, a minimum of two distinct Denisovan teams occupied the Altai area at completely different occasions, with one changing one other over hundreds of years.
The older Denisovan additionally carried extra Neanderthal DNA than the later one, displaying that interbreeding between these archaic people occurred repeatedly — not as uncommon accidents, however as a recurring function of life in Ice Age Eurasia.
Much more putting, the workforce discovered proof that Denisovans themselves blended with an even older, ‘super-archaic’ hominin population that break up from the human household tree earlier than the ancestors of Denisovans, Neanderthals and trendy people diverged.
“Utilizing this second Denisovan genome has proven that there was recurrent mixing between Neanderthals and Denisovans within the Altai area, however that these blended populations had been changed by Denisovans from elsewhere, supporting the concept Denisovans had been widespread and that the Altai could have been on the fringe of their geographic vary,” the researchers stated.
The Denisova 25 genome additionally helps resolve a long-standing puzzle about Denisovan ancestry in folks residing right now.
Fashionable populations in Oceania, elements of South Asia and East Asia all carry Denisovan DNA — however not the identical form.
By evaluating Denisovan genetic segments in hundreds of present-day genomes, the scientists recognized a minimum of three distinct Denisovan sources.
One group, intently associated to the later Denisovan genome, contributed ancestry extensively throughout East Asia and past.
A second, extra deeply divergent Denisovan inhabitants contributed DNA independently to the ancestors of Oceanians and to South Asians.
Crucially, East Asians don’t carry this deeply divergent Denisovan ancestry, suggesting their ancestors took a unique migration route into Asia — probably from the north — whereas the ancestors of Oceanians moved by way of South Asia earlier.
“Neanderthal-like DNA segments are shared amongst all populations, together with Oceanians, in line with a single out-of-Africa occasion, however unbiased Denisovan gene flows recommend a number of migrations into Asia,” the scientists stated.
A portrait of a juvenile feminine Denisovan based mostly on a skeletal profile reconstructed from historic DNA methylation maps. Picture credit score: Maayan Harel.
In line with the workforce, some Denisovan genetic variants had been probably useful and rose to excessive frequency in trendy people by way of pure choice.
Utilizing the 2 Denisovan genomes, the authors recognized dozens of areas in right now’s populations that seem to have been formed by Denisovan introgression, significantly in Oceania and South Asia.
Different Denisovan genetic modifications provide tantalizing clues to what these historic people could have appeared like.
A number of Denisovan-specific mutations have an effect on genes linked to cranial form, jaw projection and facial options — traits that align with the restricted fossil proof attributed to Denisovans.
One regulatory change sits close to FOXP2, a gene concerned in mind growth and speech and language in trendy people, elevating new questions on Denisovan cognition — although the researchers warning that genetic hints can’t substitute for direct fossil or archaeological proof.
“The consequences of introgressed Denisovan alleles on trendy human phenotypes may present some hints into Denisovan biology,” the researchers stated.
“Utilizing alleles which were related to phenotypes in trendy people, we recognized 16 associations with 11 Denisovan alleles, together with peak, blood strain, monocyte depend, and ranges of ldl cholesterol, hemoglobin and C-reactive protein.”
“We additionally recognized 305 expression quantitative trait loci (QTL) and 117 different splicing QTL affecting gene expression in trendy people throughout nineteen tissues, the strongest results embody eQTLs in thyroid, arterial tibial, testis and muscle.”
“These molecular results will be leveraged to discover additional phenotypes not preserved within the fossil file, and this up to date catalogue supplies a extra dependable foundation for exploring Denisovan traits, diversifications, and illness susceptibilities, a few of which can have been contributed to present-day people by way of admixture.”
A preprint of the team’s paper was posted on bioRxiv.org on October 20, 2025.
_____
Stéphane Peyrégne et al. 2025. A high-coverage genome from a 200,000-year-old Denisovan. bioRxiv, doi: 10.1101/2025.10.20.683404
