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Scientists Decode 200,000-Year-Old Denisovan Genome: Unraveling Ancient Human Ancestry

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A groundbreaking research team at the Max Planck Institute for Evolutionary Anthropology has successfully generated a high-quality Denisovan genome assembly using ancient DNA extracted from molar teeth found in the Denisovan Cave. This genome, dating back approximately 200,000 years, significantly predates the only previously sequenced Denisovan specimen. The findings are prompting a reevaluation of when and where early human groups interacted, mixed, and migrated throughout Asia.

Artist’s concept of Penghu Denisovans walking under the bright sun during the Pleistocene in Taiwan. Image credit: Cheng-Han Sun.

Dr. Stéphane Peregne, an evolutionary geneticist from the Max Planck Institute for Evolutionary Anthropology, along with his team, recovered this Denisovan genome from molars excavated in the Denisova Cave, located in the Altai Mountains of southern Siberia. This cave is historically significant as it was the site where Denisovans were first discovered in 2010 through DNA analysis of finger bones.

This cave continues to be pivotal in the study of human evolution, revealing repeated occupations by Denisovans, Neanderthals, and even offspring resulting from the interbreeding of these groups.

“The Denisovans were first identified in 2008 based on ancient DNA sourced from Denisova 3, a phalanx found in the Denisova Cave,” Dr. Peregne and his colleagues noted.

“This analysis confirms that Denisovans are closely related to Neanderthals, an extinct human group that thrived in Western Eurasia during the mid-to-late Pleistocene.”

Since then, twelve fragmentary remains and a single skull have been associated with Denisovans through DNA or protein analysis, with Denisova 3 being the only specimen yielding a high-quality genome.

The newly studied molars, belonging to a Denisovan male who lived approximately 200,000 years ago, are predating modern humans’ migration out of Africa.

“In 2020, a complete upper left molar was found in Layer 17, one of the oldest cultural layers within the southern chamber of the Denisova Cave, dating between 200,000 and 170,000 years old based on photostimulated luminescence,” the scientists elaborated.

“Designated as Denisova 25, this molar resembles others found at Denisova Cave, specifically Denisova 4 and Denisova 8, and exhibits larger dimensions compared to Neanderthal and most post-Middle Pleistocene hominid molars, indicating it likely belonged to a Denisovan.”

“Two samples of 2.7 mg and 8.9 mg were extracted by drilling a hole at the cement-enamel junction of the tooth, with an additional 12 subsamples varying from 4.5 to 20.2 mg collected by carefully scraping the outer root layer using a dental drill.”

Thanks to excellent DNA preservation, researchers successfully reconstructed the genome of Denisova 25 with high coverage, matching the quality of the 65,000-year-old female Denisova 3 genome.

Denisovans likely had dark skin, in contrast to the pale Neanderthals. The image depicts a Neanderthal. Image credit: Mauro Cutrona.

Comparisons between the genomes indicate that Denisovans were not a singular, homogeneous population.

Instead, at least two distinct Denisovan groups inhabited the Altai region at various intervals, with one group gradually replacing the other over millennia.

Earlier Denisovans possessed a greater amount of Neanderthal DNA than later populations, suggesting that interbreeding was a regular event rather than an isolated occurrence in the Ice Age landscape of Eurasia.

Even more intriguing, the study uncovered evidence that Denisovans engaged in interbreeding with “hyperarchaic” hominin groups that diverged from the human lineage before the ancestors of Denisovans, Neanderthals, and modern humans branched off.

“This second Denisovan genome illustrates the recurrent admixture between Neanderthals and Denisovans in the Altai region, suggesting these mixed populations were eventually supplanted by Denisovans from other regions, reinforcing the notion that Denisovans were widespread and that populations in the Altai may have existed at the periphery of their geographic range,” the researchers explained.

The Denisovan 25 genome presents valuable insights into the long-standing mysteries regarding the Denisovan ancestry in contemporary populations.

People in Oceania, parts of South Asia, and East Asia all carry Denisovan DNA, albeit from different Denisovan sources.

Through genetic comparison, scientists have identified at least three separate Denisovan origins, highlighted by their genetic segments found in thousands of modern genomes.

One lineage closely relates to the later Denisovan genome and is linked to widespread ancestry across East Asia and beyond.

A second, more distantly related Denisovan population contributed independently to Oceanian and South Asian ancestry.

Notably, East Asians do not share this highly divergent Denisovan ancestry, implying their ancestors may have taken a different route into Asia, potentially from the north, whereas Oceanian ancestors likely migrated through South Asia.

“Neanderthal-like DNA fragments appear in all populations, including Oceanians, aligning with a singular out-of-Africa migration; however, the distinct Denisovan gene flow points to multiple migrations into Asia,” the researchers stated.

Reconstruction of a young Denisovan woman based on skeletal profiles derived from ancient DNA methylation maps. Image credit: Maayan Harel.

The researchers believe certain Denisovan genetic traits offered advantages that increased their prevalence in modern human populations through the process of natural selection.

By analyzing both Denisovan genomes, the authors pinpointed numerous regions in present-day populations that appear to have originated from Denisovan introgression, particularly in Oceania and South Asia.

Genetic alterations observed in other Denisovans provide intriguing insights into their physical appearances.

Several unique mutations in Denisovans influence genes connected to cranial shape, jaw protrusion, and facial characteristics—attributes that align with the limited fossil record associated with Denisovans.

A shift in regulatory mechanisms is on the horizon. The Fox P2 gene, implicated in brain development and language in modern humans, raises important questions regarding the cognitive capabilities of Denisovans, although researchers emphasize that genetic data cannot replace direct fossil or archaeological evidence.

“The impact of Denisovan alleles on modern human phenotypes might also shed light on Denisovan biology,” the researchers pointed out.

“Examining alleles linked to contemporary human traits, we identified 16 associations with 11 Denisovan alleles, covering aspects like height, blood pressure, cholesterol levels, and C-reactive protein levels.”

“Additionally, we recognized 305 expressed quantitative trait loci (QTL) and 117 alternative splicing QTLs that affect gene expression across 19 tissues in modern humans, with the most significant effects observable in the thyroid, tibial artery, testis, and muscle tissues.”

“These molecular effects can be utilized to explore additional phenotypes that are not retained in the fossil record. This updated catalog provides a more reliable foundation for investigating Denisovan traits, adaptations, and disease susceptibilities, some of which may have influenced modern humans through admixture.”

A Preprint of the team’s research paper was published in bioRxiv.org on October 20, 2025.

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Stephane Peregne et al. 2025. High coverage genome of Denisovans from 200,000 years ago. BioRxiv doi: 10.1101/2025.10.20.683404

Source: www.sci.news

Denisovan DNA Might Have Aided Ancient Survival in the Americas

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Thousands of years ago, ancient Homo sapiens embarked on a perilous journey, traversing the icy expanses of the Bering Straits into the uncharted territories of the Americas. Recent research indicates that these migrants may have brought with them an extraordinary gift – MUC19 genes inherited from Denisovans, which could have played a pivotal role in helping humans adapt to the challenges of their new environments.

The concept of artist Peng Denisovan walking under the bright sun during the Pleistocene of Taiwan. Image credit: Cheng-Han Sun.

The modern human genome harbors a few archaic variants that are the remnants of past interbreeding events with Neanderthals and Denisovans.

While many of these variants are neutral, certain archaic mutations found in modern humans are believed to be targets of positive natural selection, possibly essential for human adaptation as they expanded into new lands.

The populations in the Americas encountered diverse environments, creating numerous opportunities for natural selection to favor archaic variations in these new settings.

This new research, spearheaded by a team from the University of Colorado, Boulder, and Brown University, focused on a gene known as MUC19, which aids in the production of proteins that form saliva and mucosal barriers in the respiratory and gastrointestinal tracts.

The researchers found that a Denisovan variant of MUC19 exists in the DNA of modern Latin Americans with Indigenous American ancestry, as well as in individuals excavated from archaeological sites across North and South America.

The prevalence of this gene in modern human populations suggests it was under significant natural selection, indicating that it conferred survival or reproductive advantages to those who carried it.

Although the specific benefits remain unclear, given the gene’s involvement in immune processes, it may have provided an enhanced defense against pathogens encountered by early settlers in the Americas.

“From an evolutionary perspective, this discovery illustrates how ancient interbreeding can produce effects that persist today,” stated Professor Emilia Fuerta Sanchez of Brown University.

“Biologically, it identifies genes that seem to be adaptable, though their precise functions are yet to be elucidated.”

“We hope this will spur further research into the actual roles of this gene.”

Limited information exists about Denisovans, who inhabited Asia between 300,000 and 30,000 years ago, with our knowledge primarily derived from small fossils found in Denisova Cave, two jawbones discovered in Tibet and Taiwan, and an almost complete skull unearthed in China this year.

Fossils from Siberian fingers contained ancient DNA, facilitating the search for genetic similarities between Denisovans and modern humans.

Previous studies have indicated that the Denisovan-derived gene EPAS1 may have contributed to the remarkable adaptations of Sherpas and other Tibetans.

In the current study, researchers compared Denisovan DNA with the most recent genomes obtained from the 1,000 Genomes Project, a global study on genetic variations.

They found that Denisovan-derived MUC19 variants are prevalent among Latino populations with Indigenous American ancestry.

The researchers also investigated DNA from 23 individuals excavated from archaeological sites in Alaska, California, Mexico, and other parts of the Americas, finding that Denisovan-derived variants were also common in these ancient peoples.

The authors conducted several independent statistical tests demonstrating that Denisovan MUC19 genetic mutations have reached unusually high frequencies in both ancient indigenous populations and present-day indigenous peoples, indicating genes that are situated on long stretches of archaic DNA.

They also revealed that the gene likely crossed over from Denisovans to another archaic population.

“These findings reveal that past interbreeding has introduced new and potentially advantageous genetic variations into human lineages,” Professor Fuerta Sanchez remarked.

“New genetic variations typically arise through slow evolutionary processes.”

“However, these interbreeding events were a sudden means of introducing a plethora of new variations.”

“In this instance, the novel genetic reservoir seems to have aided modern humans migrating to the Americas and may have bolstered their immune systems.”

“Clearly, this gene was advantageous for these populations.”

“We hope that recognizing the significance of these genes will inspire new investigations into their functions to uncover fresh biological mechanisms, particularly relating to coding genetic variants that modify protein sequences.”

Study published in the journal Science.

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Fernando A. Villania et al. 2025 MUC19 Genes: The evolutionary history of recurrent variants and natural selection. Science 389 (6762); doi:10.1126/science.adl0882

Source: www.sci.news

New Research Indicates Harbin Fossils Are Linked to Denisovan Population

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The renowned “Harbinclanium” dates back at least 146,000 years, previously classified as a distinct species: Homo Longhi.

Reconstruction of Harbin’s individuals in his habitat. Image credit: Chuang Zhao.

The skull of Harbin was unearthed in 1933 during the construction of a bridge over the Songhua River in Harbin city, Jiangxi Province, China.

Due to systematic recovery processes over extensive periods, precise locations and data pertaining to the fossil layers were unfortunately lost.

The fossils are notably large, surpassing all other archaic humans, exhibiting a low and elongated shape that lacks the rounded contours typical of modern human crania.

Features include a large, nearly square eye socket, a pronounced brow ridge, a wide mouth, and prominent teeth.

The cranial capacity is estimated at 1,420 mL, aligning within the ranges of Homo sapiens, Neanderthals, and surpassing earlier Homo species.

This specimen, often referred to as the “Dragon Man” fossil, likely represents individuals under the age of 50.

In a recent study, Dr. Qiaomiei Fu from the Chinese Academy of Sciences and his colleague from the Institute for Vertebrate Paleontology and Paleontology performed a detailed analysis of the fossils and their dental calculus.

They identified over 308,000 peptides, around 20,000 proteins, and confirmed the presence of 95 endogenous proteins.

Additionally, they found 122 single amino acid polymorphisms (SAPs) unique to humanity, reaffirming the classification of the Harbin specimens within the Homo genus.

Significantly, three variants unique to Denisovans were identified, establishing a phylogenetic connection between the Harbin fossil and Denisova 3, small fragments from Denisova Cave.

“Prior to this discovery, Denisovan fossils were sparse and fragmented, complicating our understanding of their morphology and evolutionary background,” the researchers stated.

“The Harbin Fossils, identified as a new species Homo Longhi, exhibit crucial morphological similarities to Denisovan remains found elsewhere.”

Harbin’s personal portrait. Image credit: Cicero Moraes, doi: 10.6084/m9.figshare.24648591.

The researchers also successfully extracted mitochondrial DNA (mtDNA) from the dental calculus of the fossil.

The findings confirmed that Harbin individuals belonged to the early mtDNA lineage of Denisovans.

“The mtDNA aligns with the variability observed in Denisovan mtDNA and is associated with the lineage carried by early Denisovan individuals in southern Siberia, previously identified in Denisova Caves,” the authors mentioned.

“This indicates that Denisovans occupied a broad geographical range across Asia during the mid-Pleistocene.”

The detection of Denisovan mtDNA in Harbin’s skull aids in linking Denisovans with distinct morphological traits and recognizing other specimens as Denisovan, particularly when ancient DNA is either poorly preserved or challenging to procure.

For instance, fossils from Dali, Jinniushan, and Hualongdong display comparable morphological features to the Harbin skull, suggesting they may represent the Denisovan population.

“The connection between Denisovan mtDNA and Harbin skull morphology enhances our understanding of the morphological relationships between Denisovans and other central Pleistocene fossils in East Asia,” the researchers concluded.

“Moreover, exploring host DNA from dental calculus opens new avenues for genetic research related to the mid-Pleistocene.”

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Qiaomei Fu et al. Harbin’s personal proteome from the late Pleistocene. Science published online on June 18th, 2025. doi:10.1126/science.adu9677

Qiaomei Fu et al. Denisovan mitochondrial DNA from the dental calculus of the Harbin skull, over 146,000 years old. Cell published online on June 18th, 2025. doi: 10.1016/j.cell.2025.05.040

Source: www.sci.news

Denisovan Expands its Territory to the Pacific Coast of Asia

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For decades, fishermen sailing off the coast of Taiwan have occasionally discovered bones from other large mammals that lived tens of thousands of years ago, such as elephants, buffaloes, and other large mammals.

However, in 2010, Taiwanese paleontologists were presented with a particularly strange discovery. This fossil looks like half the jaw of a gorilla. Scientists have been baffled by it ever since.

The mystery of the underwater jaw has now been solved. Wednesday, the researchers team made an announcement that it was part of Denisovan, a member of the mystical human lineage associated with the Neanderthals. This finding greatly expands the range of well-identified denisovan fossils previously known from Siberia and Tibet.

“Indeed, Denisovan was east all the way to the coast,” says Frido Welker, a molecular anthropologist and author of the new study.

Chun-hsiang Chang, a paleontologist at the National Museum of Natural Sciences of Taiwan, first learned about the jaws from a private collector in 2010. After examining it, he quickly determined that it did not belong to a gorilla, as gorillas and other apes have U-shaped jaws. Instead, the fossil jaws were angled outward from the jaw, just like ours.

However, the jaws were missing the prominent jaws seen in modern-day humans. “At the time, I thought it looked human, but not like modern-day human,” Dr. Chang said. “I thought it was very important, so I pushed the private collector to lend it to my museum.”

Over the next five years, Dr. Chang studied the jaw anatomy, working with an international group of scientists. Its shape resembles the jaws of extinct relatives of humans known to have lived in Asia for over a million years. However, Penghu 1 also had distinctive features, including large teeth.

Determining the age of Penghu 1 was also a challenge, as they were not sure exactly where Dr. Chang discovered it on the seabed. He and his colleagues analyzed the chemistry of the jaw and discovered that it resembles that of fossils of hyena species that evolved in East Asia about 400,000 years ago.

At that time, Taiwan was separated from the mainland by water. However, 190,000 years ago, sea levels fell sufficiently to create a land bridge that lasted until 130,000 years ago. The ocean then rose again until 70,000 years ago. This pattern continued until 10,000 years ago when another land bridge formed. Dr. Chang and his colleagues believe that Penghu 1 lived in one of these periods when sea levels were lower.

One possibility was that Penghu 1 belonged to a mysterious group of humans called Denisovans. Researchers discovered Denisovan in 2010 while examining fossils from the Siberian Denisova Cave. The bones of teeth and fingers contain ancient DNA with unusual mutations, revealing previously unknown human strains.

Subsequent research shows that Denisovans, Neanderthals, and modern humans share common ancestors who lived in Africa about 600,000 years ago. The Neanderthal and Denisovan ancestors migrated from Africa, and then these two lineages split about 400,000 years ago, with the Neanderthals spreading to Europe in the west.

Denisovan’s spread was difficult to chart. For years, the only known Denisovan fossils have been teeth and bone fragments found in Denisova caves. However, a valuable clue comes from living humans. Many people in East Asia and the Pacific today have small amounts of Denisovan DNA, suggesting that Denisovans must have interbred with East Asian Homo sapiens before their extinction and lived far beyond Siberia.

Dr. Chang and his colleagues noticed that the teeth in the Penghu 1 jaw resemble the teeth found in the Denisova Cave. But those clues were not enough to link them. They attempted to search for DNA in their jaws but found nothing. This was not surprising given that the Penghu 1 fossils had been sitting on the seabed for thousands of years.

After Dr. Chan’s team revealed their analysis in 2015, Penghu 1 became an even more enigmatic, human-like fossil at the museum. “Our research was stagnant,” Dr. Chan said.

Over the next few years, Dr. Welker and other researchers pioneered ways to recover ancient proteins from fossils. They discovered that even if a fossil loses all its DNA, it could still retain protein fragments.

Using such methods, Dr. Welker studied the 160,000-year-old jaws found in a high-altitude cave in Tibet. In 2019, the team reported that Tibetan fossils contained fragments of ancient collagen and other proteins.

These proteins resemble modern human proteins but also exhibit differences indicating that the jaw belonged to a Denisovan.

With that discovery, Dr. Welker searched other Asian fossil scientific literature for jaws resembling the Tibetan jaws that could be tested for proteins.

“That’s when the lower jaw of Penghu came on my radar,” he said.

Both the Tibetan and Taiwanese jaws had very large teeth. Dr. Welker and his colleagues reached out to Dr. Chang. In 2023, Dr. Chang and his team flew to Copenhagen with their jaws. Analysis of the results revealed protein fragments that were only present in Denisovans.

“Since the first publication of Penghu’s lower jaw, many of us thought it might be Denisovan, mainly based on being in the right place at the right time,” said Bens Viola, a paleontologist at the University of Toronto, who was not involved in the study. “But of course, assumptions are assumptions, and we need actual data to validate them.”

Another clue came from fragments of enamel protein in the teeth. Modern humans carry enamel genes on the X chromosome, while men carry slightly different enamel genes on the Y chromosome. Denisovan was carrying the Y-chromosome version, indicating that it belonged to a male adult.

The two Denisovan jaw anatomy may turn out to be a hallmark of male Denisovan. Women’s Denisovan may have a thinner anatomy, but scientists will need more evidence to know for sure.

The discovery of other Denisovan fossils could expand the scope of humanity. In 2022, researchers found teeth from 160,000 years ago in a cave in Laos. They resemble the teeth of the jaw in Tibetan Denisovan. Anyone who lived there would have had to survive in the tropical forests far from Siberia.

However, Laos’ teeth do not contain DNA, and the protein fragments did not clarify the type of human it belonged to. However, the cave and its neighbors still retain many teeth that have not been fully analyzed. Other traces of Denisovan may not have been found in the museum yet.

But so far, evidence reveals that Denisovans were able to thrive for thousands of miles and in a variety of environments. Janet Kelso, a paleontologist at the Max Planck Institute for Evolutionary Anthropology, was impressed by the differences between the Penghu 1 protein and the protein found in Tibet. As Denisovans expanded throughout different environments, they adapted and became genetically distinct populations.

“There’s still a lot to learn about Denisovan,” she said.

Source: www.nytimes.com

Study finds evidence of multiple instances of Denisovan populations interbreeding with modern humans

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The identification of a new human group called the Denisovans has been one of the most exciting discoveries in human evolution over the past decade. Unlike Neanderthal remains, the Denisovan fossil record consists of only a few skeletal fragments. Several Denisovan populations, which likely had vast geographic ranges, adapted to different environments and through multiple different interbreeding events that helped shape early human history, according to a new study. I passed on some of my genes.

Portrait of a young Denisovan woman based on a skeletal profile reconstructed from ancient DNA methylation maps. Image credit: Maayan Harel.

Denisovans are an extinct hominin group first identified through genome sequences determined from finger bone fragments found in the Denisova Cave in the Altai Mountains of southern Siberia.

“This was one of the most exciting discoveries in human evolution in the past decade,” said Dr Linda Ongaro, a researcher at Trinity College Dublin.

Subsequent genome analysis showed that Denisovans diverged from Neanderthals 400,000 years ago, and that at least two distinct Denisovan populations intermingled with the ancestors of modern Asians.

The only physical remains of Denisovans discovered so far are a finger bone fragment, three teeth, and a skull fragment from the Denisovan Cave. Jaw bones and rib bones from Baisiya Karst Cave on the northeastern edge of the Tibetan Plateau.

“It's a common misconception that humans evolved suddenly and cleanly from one common ancestor, but the more we learn, the more we realize that interbreeding with different hominins occurred and helped shape the humans we know today. ” said Dr. Ongaro.

“Unlike Neanderthal remains, the Denisovan fossil record consists only of finger bones, jaw bones, teeth, and skull fragments.”

“However, by exploiting the remaining Denisovan parts of modern humans' genomes, scientists have found evidence of at least three past events in which genes from different Denisovan populations invaded modern humans' genetic characteristics. I discovered.”

Each of these shows different levels of relatedness to the sequenced Altai Denisovans, illustrating the complex relationships between these sister lineages.

Dr. Ongaro and his colleague Professor Emilia Huerta Sánchez of Trinity College Dublin and Brown University, in their new paper, have a wide geographical range, from Siberia to Southeast Asia, and from Oceania to the south. We have reviewed evidence pointing to several likely Denisovan populations. America has adapted to a unique environment.

They also outlined a number of genes of Denisovan origin that conferred advantages to modern humans in different environments.

“Among these are genetic loci that confer tolerance to hypoxia or hypoxic conditions, which makes a lot of sense because we see it in the Tibetan population. Multiple genes that increase immunity. Another “Influences lipid metabolism and provides heat when stimulated by cold, providing benefits to Arctic Inuit populations,” Dr. Ongaro said.

“There are many directions for future research that will help us more fully understand how Denisovans influenced modern humans, including uncovering currently hidden traces of Denisovan ancestry. This includes more detailed genetic analyzes in understudied populations that have the potential to

“Additionally, by integrating more genetic data with archaeological information, finding more Denisovan fossils will certainly fill in some more gaps.”

of paper Published in a magazine natural genetics.

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L. Ongaro & E. Huerta-Sánchez. History of multiple Denisovan introgressions in modern humans. Nat Genetpublished on November 5, 2024. doi: 10.1038/s41588-024-01960-y

Source: www.sci.news