Denisovan finger bone

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Genome of Ancient Denisovans May Help Clarify Human Evolution

Our ancestors didn’t walk alone: Neanderthals and other ancient peoples shared Earth with them tens of thousands of years ago.

Now, using new technology, scientists have sequenced with high precision the genome of one of those close but little-known relatives: an extinct people known as the Denisovans, who lived in and around modern-day Siberia.

The Denisovan genome, reported online Thursday in the journal Science, was derived from tiny quantities of shredded DNA extracted from a finger bone found in a Russian cave in 2008, as well as a tooth found later.

What is striking, scientists said, is that it is every bit as detailed as a sequence generated with a fresh blood or saliva sample from someone alive today.

Analysis of the genome and comparisons with ours and the Neanderthals’ will offer insights into the history of Homo sapiens — who we mated with, where and when — as well as the unique genetic changes that make modern humans who they are, scientists said.

Study leader Svante Paabo, a pioneer in decoding ancient genomes, said it would take biologists decades to understand the meaning of all these tiny differences.

Their analysis also suggests that the Denisovans had dark skin, brown hair and brown eyes, but scientists can’t yet say much more than that about their appearance.

The advance hinged on new techniques designed to investigate scant and highly degraded genetic material found in fossils. Their application to these and other specimens promises to draw back the curtain on our species’ complicated and much-debated history, said John Hawks, a paleoanthropologist at the University of Wisconsin in Madison, who wasn’t involved in the study.

The evolutionary path of humans is in many respects still mysterious, and the exact timing of events is uncertain. But the story goes something like this: Ancestors of humans emerged in Africa and migrated out to the rest of the world in several successive waves.

The first globe-trotter was Homo erectus, whose trek began 1 million to 2 million years ago. Then came the ancestor of the Neanderthals and Denisovans, who left Africa as far back as 800,000 years ago and replaced or interbred with descendants of Homo erectus.

The third wave of people, Homo sapiens, left Africa perhaps 100,000 years ago and sometimes mated with the Neanderthals and Denisovans they encountered. The result is you and me and everyone else on the planet.

The new genome gives scientists a sense of just how much of our genomes we owe to our extinct relatives. About 3% to 5% of the DNA in people native to Papua New Guinea, Australia, the Philippines and other islands nearby came from Denisovans, the study found, confirming reports based on a draft version of the Denisovan genome. The authors of the study didn’t find any significant contribution of Denisovans to the DNA of people from mainland Eurasia, however.

The new gene-sequencing techniques also allowed scientists to more precisely calculate how much of modern humans’ DNA came not from Denisovans but Neanderthals. They found, to their puzzlement, that Native Americans and people in East Asia have more Neanderthal DNA than do people whose ancestors are from Europe, where most Neanderthals lived.

In another first, the authors used the DNA sequence to estimate the age of the Denisovan pinkie finger bone.

They started by counting up all the tiny genetic changes that have accrued in the genomes of both modern humans and Denisovans since our lineage diverged from that of chimpanzees 6.5 million years ago. Then they compared the two numbers.

Genetic changes build up regularly through the ages, like the ticking of a clock, so the tally allows scientists to estimate the passage of time. Not surprisingly, the Denisovan sample had amassed fewer changes than its human counterparts. From the difference, the authors estimated that our ancient relative, believed to be a female child, met her end somewhere between 74,000 and 82,000 years ago.

The authors used the same approach to estimate how long ago our lineage branched away from the line that led to the Denisovans and Neanderthals. It happened somewhere between 170,000 and 700,000 years ago, they concluded.

The range is broad because the modern DNA revolution has overturned notions of how fast the internal genetic clock is ticking, said study coauthor Matthias Meyer.


New Denisovan DNA expands diversity, history of species

While the continents of Africa and Europe have been obvious and fruitful treasure troves for exploration and discovery of our modern human origins, Asia has been somewhat overlooked. Scientists have thought that modern humans left Africa about 60,000 years ago and, as they colonized Western Eurasia, found a world empty of any other archaic hominin species. This assumption stemmed in part from the fact that the prehistory of Asia is poorly known compared with that of Africa and Europe.

But research published this week in the journal Science adds more evidence to the record that Denisovans, a group of extinct hominins that diverged from Neanderthals about 400,000 years ago, may have more widely inhabited northeast central Asia.

Ancient Denisovan mitochondrial DNA has been recovered in sediments from Baishiya Karst Cave, a limestone cave at the northeast margin of the Tibetan Plateau, 3,280 meters above sea level. Samples of sediments were analyzed by an international team including Arizona State University researcher Charles Perreault. Denisovan mitochondrial DNA was recovered that has been dated from around 100,000 to 60,000 years ago, and also possibly as recently as 45,000. If true, this last date may overlap with the presence of modern humans in northeast central Asia.

Perreault is a research affiliate with the Institute of Human Origins and an associate professor with the School of Human Evolution and Social Change.

“When we started developing this project about 10 years ago,” said Perreault, “none of us expected Baishya Cave to be such a rich site. We’ve barely scratched the surface — three small excavation units have yielded hundreds of stone tools, fauna and ancient DNA. There’s a lot that remains to be done.”

A mandible fossil (the “Xiahe mandible”) from the same cave and dated to 160,000 had been previously identified, tenuously, as Denisovan, based on a single amino acid position. This current study dispels any doubt left that the Denisovans occupied the cave.

This discovery in Baishiya Karst Cave is the first time Denisovan DNA has been recovered from a location that is outside Denisova Cave in Siberia, Russia — previously the single location in the world where a handful of DNA-bearing Denisovan fossil bones had been discovered. In 2010, a finger bone belonging to a previously unknown hominin species was found buried in Denisova Cave, in the Russian Altai Mountains. Evidence of this new species forced anthropologists to revise their model of human evolution outside of Africa.

Finding Denisovan DNA on the Tibetan Plateau itself is surprising. Evidence of archaic hominins 2,000 meters above sea level is unusual. Life this high on the plateau is harsh for many reasons, including its thin air, and humans can develop altitude sickness anywhere above 2,500 meters above sea level. This suggests that the Denisovans may have evolved adaptations to high altitude, much like modern Tibetans. The dates of the sediments with mitochondrial DNA, along with the older 160,000-year-old Xiahe mandible, suggest that the Denisovans were on the plateau perhaps continuously for tens of thousands of years — more than enough for genetic adaptations to emerge.

Getting DNA samples from geographic locations outside of Siberia is also important to understand the genetic diversity and the population structure and history of the Denisovan group as a whole. Researchers suspected that Denisovans were widespread in Asia, based on the extensive Denisovan genomic signal among present-day Asians.

The Denisovan fossil and the DNA it contained indicate that early modern humans coexisted in Asia with other archaic hominin species, but, unexpectedly, that they interbred with them. Like Neanderthals, Denisovan population intermixed with modern humans as they dispersed into Asia. In fact, there’s evidence that the genetic adaptations to high altitude in present-day Tibetans come from Denisovans. If confirmed, this is a great example of how intermixing with local archaic populations has shaped, and helped, the spread of modern humans around the world. In this case, it allowed humans to colonize the Tibetan Plateau perhaps faster than they would otherwise have been able to.

“Baishiya Cave is an extraordinary site that holds tremendous potential to understand human origins in Asia,” Perreault said. “Future work in Baishiya Cave may give us a truly unique access to Denisovan behavior and solidifies the picture that is emerging, which is that Denisovans, like Neanderthals, were not mere offshoots of the human family tree — they were part of a web of now-extinct populations that contributed to the current human gene pool and shaped the evolution of our species in ways that we are only beginning to understand.”


DNA Mystery

The results also underscore the innovative genetics that anthropologists are increasingly using to pull back the veil of time. “This is a great paper that represents the new cutting-edge science of paleoanthropology,” says Pontus Skoglund, a postdoctoral researcher at Harvard University who wasn’t involved with the study.

Susanna Sawyer of the Max Planck Institute for Evolutionary Anthropology led the genetic effort to describe and date the recently found tooth.

Her team homed in on the tooth’s mitochondrial DNA, a portion of genetic material that holds up better in fossils over time.

But finding a clean piece of Denisovan DNA wasn’t easy. Sawyer and Pääbo had to identify and rule out contamination from modern humans, modern and ancient bacteria, and ancient hyenas, which seem to have long prowled the cave.

Once Sawyer had the new tooth’s mitochondrial DNA in hand, she was able to verify that it indeed was Denisovan. The new DNA also allowed Sawyer to reconstruct the mitochondrial genome of the common ancestor of the three individuals found in the cave.

The common ancestor’s DNA provided the team with an important baseline, calibrating a genetic stopwatch that accrues mutations with each tick. Denisovans who died closer to the common ancestor’s time would have fewer mutations in their genomes than more recent Denisovans would. Sawyer found that the recently discovered tooth had half the number of mutations of the other remains, suggesting it was older.

The discrepancy suggests that the Denisovan to whom the tooth belonged lived about 60,000 years before the individuals who left behind the finger bone and the other tooth. At a minimum, this miniature family tree shows that the Denisovans were a single biological group that sporadically inhabited the region for at least as long as modern humans have.

“The world at that time must have been far more complex than previously thought,” says Sawyer. “Who knows what other hominids lived and what effects they had on us?”


Denisovan discovery

The mystery surrounding the lost piece began in a remote valley at the foot of the Altai Mountains in southern Siberia, where Russian archaeologists excavating the Denisova Cave uncovered a finger bone belonging to a group of ancient humans in 2008. Anatoly Derevianko, who is an archaeologist at the Russian Academy of Sciences Institute of Archeology and Ethnography in Novosibirsk and was leading the dig, decided to divide the bone and send the pieces to two labs to see whether DNA could be extracted from either half.

One of the fragments went to Svante Pääbo, an evolutionary geneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. His team sequenced its DNA and discovered that the bone belonged to a lineage distinct from modern humans and from Neanderthals. In January 2010, Pääbo and several of his colleagues flew to Novosibirsk.

Use ancient remains more wisely

That’s when Derevianko told Pääbo’s team that he had divided the bone in two and sent the other half to Edward Rubin, a geneticist then at Lawrence Berkeley National Laboratory (LBNL) in California, whose team had been competing with Pääbo’s to sequence Neanderthal DNA.

“We freaked out a bit,” remembers Viola, who joined Pääbo on the trip. “We had no idea there was this second part.”

Worried about getting scooped, Pääbo and his team raced to report their discovery. They published the fossil’s mitochondrial genome — a short stretch of maternally inherited DNA — in March 2010 2 . Several months later, they went on to reveal the first complete nuclear genome of a Denisovan 3 . The studies showed that Denisovans were a group of extinct hominins that were more closely related to Neanderthals than to modern humans, and that they lived in the Siberian cave — and probably across Asia — more than 30,000 years ago.

The whereabouts of the missing bone fragment are still unclear. Credit: Eva-Maria Geigl

The 2010 finding transformed the cave into one of the world’s most important archaeological sites. Researchers have since found more ancient-human bones in the cave, including the stunning discovery of a first-generation hybrid, which had a Neanderthal mother and Denisovan father.

But Viola — who has analysed nearly every Denisovan fossil from the cave — says he never forgot about the second finger-bone fragment. “I’ve been wondering the whole time what the other half would have looked like,” he says. “All I knew is that it was in Berkeley.”


New evidence in search for the mysterious Denisovans

Replica Homo erectus skull from Jav. Credit: Trustees of Natural History Museum

An international group of researchers led by the University of Adelaide has conducted a comprehensive genetic analysis and found no evidence of interbreeding between modern humans and the ancient humans known from fossil records in Island Southeast Asia. They did find further DNA evidence of our mysterious ancient cousins, the Denisovans, which could mean there are major discoveries to come in the region.

In the study published in Nature Ecology and Evolution , the researchers examined the genomes of more than 400 modern humans to investigate the interbreeding events between ancient humans and modern human populations who arrived at Island Southeast Asia 50,000–60,000 years ago.

In particular, they focused on detecting signatures that suggest interbreeding from deeply divergent species known from the fossil record of the area.

The region contains one of the richest fossil records (from at least 1.6 million years) documenting human evolution in the world. Currently there are three distinct ancient humans recognized from the fossil record in the area: Homo erectus, Homo floresiensis (known as Flores Island hobbits) and Homo luzonensis.

These species are known to have survived until approximately 50,000–60,000 years ago in the cases of Homo floresiensis and Homo luzonensis, and approximately 108,000 years for Homo erectus, which means they may have overlapped with the arrival of modern human populations.

The results of the study showed no evidence of interbreeding. Nevertheless, the team were able to confirm previous results showing high levels of Denisovan ancestry in the region.

Lead author and ARC Research Associate from the University of Adelaide Dr. João Teixeira, said: "In contrast to our other cousins the Neanderthals, which have an extensive fossil record in Europe, the Denisovans are known almost solely from the DNA record. The only physical evidence of Denisovan existence has been a finger bone and some other fragments found in a cave in Siberia and, more recently, a piece of jaw found in the Tibetan Plateau."

"We know from our own genetic records that the Denisovans mixed with modern humans who came out of Africa 50,000–60,000 years ago both in Asia, and as the modern humans moved through Island Southeast Asia on their way to Australia.

"The levels of Denisovan DNA in contemporary populations indicates that significant interbreeding happened in Island Southeast Asia.

"The mystery then remains, why haven't we found their fossils alongside the other ancient humans in the region? Do we need to re-examine the existing fossil record to consider other possibilities?" says Dr. João Teixeira.

Co-author Chris Stringer of the Natural History Museum in London added: "While the known fossils of Homo erectus, Homo floresiensis and Homo luzonensis might seem to be in the right place and time to represent the mysterious 'southern Denisovans," their ancestors were likely to have been in Island Southeast Asia at least 700,000 years ago. Meaning their lineages are too ancient to represent the Denisovans who, from their DNA, were more closely related to the Neanderthals and modern humans."

Co-author Prof Kris Helgen, Chief Scientist and Director of the Australian Museum Research Institute, said: "These analyzes provide an important window into human evolution in a fascinating region, and demonstrate the need for more archaeological research in the region between mainland Asia and Australia."

Helgen added: "This research also illuminates a pattern of 'megafaunal' survival which coincides with known areas of pre-modern human occupation in this part of the world. Large animals that survive today in the region include the Komodo Dragon, the Babirusa (a pig with remarkable upturned tusks), and the Tamaraw and Anoas (small wild buffalos).

"This hints that long-term exposure to hunting pressure by ancient humans might have facilitated the survival of the megafaunal species in subsequent contacts with modern humans. Areas without documented pre-modern human occurrence, like Australia and New Guinea, saw complete extinction of land animals larger than humans over the past 50,000 years."

Dr. Teixeira said: "The research corroborates previous studies that the Denisovans were in Island Southeast Asia, and that modern humans did not interbreed with more divergent human groups in the region. This opens two equally exciting possibilities: either a major discovery is on the way, or we need to re-evaluate the current fossil record of Island Southeast Asia."

"Whichever way you choose to look at it, exciting times lie ahead in palaeoanthropology."


New Denisovan DNA expands diversity, history of species

While the continents of Africa and Europe have been obvious and fruitful treasure troves for exploration and discovery of our modern human origins, Asia has been somewhat overlooked. Scientists have thought that modern humans left Africa about 60,000 years ago and, as they colonized Western Eurasia, found a world empty of any other archaic hominin species. This assumption stemmed in part from the fact that the prehistory of Asia is poorly known compared with that of Africa and Europe.

But research published this week in the journal Science adds more evidence to the record that Denisovans, a group of extinct hominins that diverged from Neanderthals about 400,000 years ago, may have more widely inhabited northeast central Asia.

Ancient Denisovan mitochondrial DNA has been recovered in sediments from Baishiya Karst Cave, a limestone cave at the northeast margin of the Tibetan Plateau, 3,280 meters above sea level. Samples of sediments were analyzed by an international team including Arizona State University researcher Charles Perreault. Denisovan mitochondrial DNA was recovered that has been dated from around 100,000 to 60,000 years ago, and also possibly as recently as 45,000. If true, this last date may overlap with the presence of modern humans in northeast central Asia.

Perreault is a research affiliate with the Institute of Human Origins and an associate professor with the School of Human Evolution and Social Change.

“When we started developing this project about 10 years ago,” said Perreault, “none of us expected Baishya Cave to be such a rich site. We’ve barely scratched the surface — three small excavation units have yielded hundreds of stone tools, fauna and ancient DNA. There’s a lot that remains to be done.”

A mandible fossil (the “Xiahe mandible”) from the same cave and dated to 160,000 had been previously identified, tenuously, as Denisovan, based on a single amino acid position. This current study dispels any doubt left that the Denisovans occupied the cave.

This discovery in Baishiya Karst Cave is the first time Denisovan DNA has been recovered from a location that is outside Denisova Cave in Siberia, Russia — previously the single location in the world where a handful of DNA-bearing Denisovan fossil bones had been discovered. In 2010, a finger bone belonging to a previously unknown hominin species was found buried in Denisova Cave, in the Russian Altai Mountains. Evidence of this new species forced anthropologists to revise their model of human evolution outside of Africa.

Finding Denisovan DNA on the Tibetan Plateau itself is surprising. Evidence of archaic hominins 2,000 meters above sea level is unusual. Life this high on the plateau is harsh for many reasons, including its thin air, and humans can develop altitude sickness anywhere above 2,500 meters above sea level. This suggests that the Denisovans may have evolved adaptations to high altitude, much like modern Tibetans. The dates of the sediments with mitochondrial DNA, along with the older 160,000-year-old Xiahe mandible, suggest that the Denisovans were on the plateau perhaps continuously for tens of thousands of years — more than enough for genetic adaptations to emerge.

Getting DNA samples from geographic locations outside of Siberia is also important to understand the genetic diversity and the population structure and history of the Denisovan group as a whole. Researchers suspected that Denisovans were widespread in Asia, based on the extensive Denisovan genomic signal among present-day Asians.

The Denisovan fossil and the DNA it contained indicate that early modern humans coexisted in Asia with other archaic hominin species, but, unexpectedly, that they interbred with them. Like Neanderthals, Denisovan population intermixed with modern humans as they dispersed into Asia. In fact, there’s evidence that the genetic adaptations to high altitude in present-day Tibetans come from Denisovans. If confirmed, this is a great example of how intermixing with local archaic populations has shaped, and helped, the spread of modern humans around the world. In this case, it allowed humans to colonize the Tibetan Plateau perhaps faster than they would otherwise have been able to.

“Baishiya Cave is an extraordinary site that holds tremendous potential to understand human origins in Asia,” Perreault said. “Future work in Baishiya Cave may give us a truly unique access to Denisovan behavior and solidifies the picture that is emerging, which is that Denisovans, like Neanderthals, were not mere offshoots of the human family tree — they were part of a web of now-extinct populations that contributed to the current human gene pool and shaped the evolution of our species in ways that we are only beginning to understand.”


Written in Bone: The Denisovans

The Denisovans, one of our early human relatives, are known only from a finger bone, two teeth, and the ghostly remnants of their DNA inside our own genome.

Skull of Homo heidelbergensis

In 2008, Russian scientists from the Institute of Archaeology and Ethnology of Novosibirsk began excavations at a site along the Anuy River in the Altai Mountains, near the borders of Mongolia and China. Known as Denisova Cave after a religious hermit who had lived there in the 1700’s, the cave had been intermittently occupied by both Neandertals and modern Homo sapiens for at least 125,000 years.

That July, paleontologist Alexander Tsybankov, working in a sediment layer dated to around 40,000 years old, uncovered a tiny fragment of bone about the size of an aspirin tablet that was tentatively identified as part of a bone from the little finger of a hominid, probably Homo sapiens. The growth pattern indicated it had belonged to a child about eight years old.

Although tiny, the bone was very well-preserved by the cold and dry conditions inside the cave, and the Russian team thought it might be possible to extract a DNA sample from it. So the pinkie bone was sent to the Max Planck Institute in Germany, where over the course of a year researchers were able to sequence a sample of mitochondrial DNA. They were shocked by what they found. Comparing the DNA sequence to those of known modern humans and Neandertals, they found that the sample from the Denisova Cave differed from both, by over 300 sites. The DNA did not come from Homo sapiens, and it also did not come from Homo neandertalensis. It came from something completely different—an undiscovered hominid, now known only from its DNA.

A year later, a toe bone and an odd-looking adult molar tooth was uncovered inside the cave, further down in the same sediment layer. The toe bone was examined for DNA, which turned out to match that of Neandertals. But the tooth was much larger than either a Neandertal or a modern human, and when mitochondrial DNA was successfully extracted from it and sequenced, it turned out to be from the same unknown species discovered the year before. Shortly later, a similar molar, found in the cave years earlier but misidentified as a bear tooth, yielded the same DNA.

Using different techniques, researchers now successfully extracted nuclear DNA from the earlier finger bone sample. Unlike mitochondrial DNA, which is a short loop of DNA found outside the cell nucleus and is only passed along by the mother, nuclear DNA, found in chromosomes inside the nucleus, contains the entire genotype and comes from both parents. Comparing the nuclear DNA sequences of modern humans, Neandertals and the mystery find from Denisova, investigators found that there was no Y chromosome—the young child in the cave had been a girl. But a more surprising conclusion also resulted: both the Neandertal DNA and modern human DNA contained pieces derived from the DNA found in the cave—and each of them had different pieces.

The evidence was now conclusive: the fossil teeth and finger bone found in the cave had belonged to a previously undiscovered species of hominin, which had interbred with both Neandertals and Homo sapiens. The new species became dubbed the “Denisovans”.

In total, by interpolating the Denisovan DNA segments found in the human and Neandertal genomes, geneticists were able to reconstruct over half of the Denisovan genome, enough to compare the complete sequence with that of modern living humans around the world—and they found another surprise. Already it had been known that humans outside of Africa had Neandertal genes in about 2.5% of their total DNA—the result of interbreeding that probably happened in the Middle East. Now, they found that modern humans in east Asia—particularly in New Guinea, some Pacific Islands, and parts of the Philippines—carried Denisovan genes in as much as 5% of their DNA.

According to the latest hypothesis, the predecessor of Homo sapiens, known as Homo heidelbergensis, lived in Africa about 400,000 years ago. At around that time, it migrated out of Africa and through the Middle East, then evolved into two distinct species: one species became established in Europe and became Neandertals, while the other migrated east into Asia and became Denisovans. The Denisovan DNA samples show that they had very little genetic diversity, indicating that they were probably a very small population—and shared DNA sequences show that the Denisovans must have interbred to some extent with Neandertals (less than 1%), probably at the border of their territories. Meanwhile, the heidelbergensis populations that remained in Africa evolved into modern humans, Homo sapiens, who themselves migrated out of Africa about 60,000 years ago. The sapiens population that moved into Europe encountered the Neandertals, interbred with them briefly, then replaced them. The sapiens who migrated into Asia, on the other hand, encountered the Denisovans, interbred with them, then carried those genes with them when they continued on into Southeast Asia.

And some people still carry that genetic legacy today. On the high plateau of Tibet, people have developed the capacity to efficiently extract oxygen from the cold thin air at these high altitudes—something which people from lower elevations cannot do. Geneticists knew that this ability was conferred by a gene known as EPAS1, which is found among people from the area of Tibet, but not anywhere else. It was not until the Denisovan DNA was sequenced that the mystery was solved: EPAS1 was a Denisovan gene, and had entered the Homo sapiens DNA through interbreeding. In the area of Tibet, the EPAS1 gene provided a survival advantage and was conserved through natural selection. It is not known, however, why so many Denisovan genes have been preserved in human populations of Southeast Asia, or why they were not conserved by other people in the region such as the Chinese or Japanese. It has been hypothesized that these Denisovan genes may be important in fending off certain tropical diseases.

Despite the importance of the Denisovans to human evolution, we know nothing of what they looked like, what tools they used, or what culture they had—all we know is that they had unusually large molar teeth, and they had genes for dark hair, dark eyes, and dark skin. All of the stone tools and cultural objects found in the Denisovan Cave appear to be typical of those made by Neandertals or modern humans. Some unusual-looking skulls found in China have been proposed as putative Denisovans, but since it is not possible to extract DNA from them for analysis, that remains speculation and cannot be confirmed without a genetic match.

Recently, however, yet another twist was added to the story. Geneticists who have compared the Denisovan and Neandertal genomes have concluded that they were able to detect a few sequences that appeared to have come from some other species entirely, one which had apparently contributed genes to both. This may have been an even earlier species that was encountered by both Neandertals and Denisovans as they spread across the world. So there may be yet another unknown human ancestor still to be found, suggested only by its continued presence in our genes.


Three Denisovan Groups

Perhaps the most significant way that the new genetic evidence alters our conception of the Denisovans is that it reveals them to be diverse. In some modern Indonesians, scientists found not one, but two distinct Denisovan genomic signatures. What's more, these two groups also looked different from the Denisovans previously found in Siberia, which they researchers say was another group altogether.

For those of you keeping count, that adds up to three different kinds of Denisovans spread from Siberia to across the disparate islands of Indonesia. It's a substantial expansion of Denisovans' range. Whereas scientists published evidence proving they lived in just one small cave in 2010, we now know that Denisovans ranged across thousands of miles during their time on Earth.

Being spread across so wide an area for so long probably played a role in the Denisovans' eventual diversification into multiple lineages. The three groups were bounded by two large geographical impediments: the Himalayas in the east, and the oceanic gaps between the islands that make up Indonesia today. As the researchers see it, one group of Denisovans would have lived in or around present-day Siberia, Kazakhstan and in China just north of the Himalayas. And the remains from members of this group are likely what researchers found in 2010.

But a different group of Denisovans lived in Southeast Asia, around what is now Thailand and Vietnam. The third group called the islands of Indonesia home. Those two southern groups diverged from the Siberian Denisovans over 250,000 years ago. That's before anatomically-modern humans even appeared. And at least one of these groups survived well into the late Pleistocene, dying out just tens of thousands of years ago.

"This is a very interesting article, which presents some new data that helps to round out the picture of archaic admixture in New Guinea and nearby," says Sharon Browning, a researcher at the University of Washington who studies the genomics of ancient hominins, in an email. "The finding of another introgressing Denisovan population is interesting and in line with what has been seen earlier in terms of population structure within Denisovans . It implies that several (at least three) very distinct Denisovan populations were in existence and have contributed to modern human genomes."

That means when modern humans made their way out of Africa, they were far from alone. Instead, they would have been the newcomers in many of the places they traveled to, entering the lands of hominins that had lived there for thousands of years.

"It would have been a really, really interesting time when our ancestors left Africa," Cox says. "They would have encountered people everywhere they went."

And it was more than just a meet and greet. Given their proximity, it's no surprise that mating between the two lineages occurred on more than one occasion. Modern-day humans still carry the legacy of those inter-lineage trysts in our DNA. Southeast Asians, and people from Papua New Guinea in particular, got a much richer Denisovan inheritance than the rest of us. That's probably because their ancestors lived around the ancient humans the longest. That left Papuans, an ethnic group today inhabiting the island of New Guinea, carrying genetic signatures from not one, but two lineages of Denisovans. This includes genes involved with both immunity to infectious diseases and metabolism.

"It's clear that we've actually inherited a lot of stuff from these archaic hominins, it's really affecting us biologically," Cox says.


Science Researchers Sequence the Genome of the Denisovans, A Close Relative of the Neandertals

Researchers have now described the complete sequence of the Denisovan genome, shedding light on the relationships between these archaic humans, who were closely related to Neandertals, and modern humans.

The research team, led by Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, generated a list of recent changes in the human genome that occurred after modern humans diverged from the Denisovans. This list will help scientists understand what sets modern humans apart from the Denisovans and Neandertals.

The results were published online by Science, in the 30 August edition of ScienceExpress.

Fossil evidence of the Denisovans is scanty the existence of this group only came to light in 2010 when DNA from a piece of a finger bone and two molars that were excavated at Denisova Cave in the Altai Mountains of southern Siberia was studied.

“We’ve remarkably been able to extract DNA from the Neandertals and Denisovans to compare them to ourselves,” said Laura Zahn, senior editor at the journal Science, during a 29 August press teleconference.


Replica of the Denisovan finger bone and a U.S. penny. | Image courtesy of Max Planck Institute for Evolutionary Anthropology

Because they had only a tiny sample of genetic material recovered from the finger bone, Pääbo and his research team developed a treatment that “unzipped” the ancient DNA so that each of its two strands could be used to generate molecules for sequencing. This method allowed the team to generate an extremely thorough genome sequence, similar in quality to what researchers can obtain for the modern human genome.

“We have very few errors in the sequences, even less errors than we often have when you sequence a person today,” Pääbo said. “[This genome] now allows us to look across the whole genome on all the mutations that have happened since we separated from Denisovans… such mutations that happened very recently in human history and have spread to everybody or almost everybody today.”

The researchers compared the Denisovan genome with the genomes of several modern humans from around the world. The Denisovans share more genes with populations from the islands of southeastern Asia, including Melanesia and Australian Aborigines, than with populations elsewhere in Asia.

“We can confirm… that relatives of a Denisovan individual in Denisova Cave contributed genes to the ancestors of present-day people from New Guinea, in a gene flow event that did not affect the rest of the people in mainland Eurasia,” said David Reich of Harvard Medical School and the Broad Institute in Massachusetts. “We find no trace of Denisovan genetic material in mainland Eurasia, including in mainland Southeast Asia, to the limits of our resolution.”

“However, it’s clear that Denisovan genetic material has contributed 3-5% of the genomes of people in Australia and New Guinea and Aboriginal people from the Philippines and some of the islands nearby,” Reich noted, “so we are able to confirm that quite powerfully.”

The research team, which published a draft sequence of the Neandertal genome in 2010, uncovered another surprise with the Denisova genome. “What seems to be the case is that people in the eastern parts of Eurasia, in Native Americans, have more Neandertal material than people in Europe, even though Neandertals mostly lived in Europe,” Reich said, “which is really, really interesting, and we were not able to detect this before in our paper we published in 2010.”

The researchers also concluded that the Denisovan individual whose genome was sequenced carried genetic variants that in present-day humans are associated with dark skin, brown hair, and brown eyes, and that the genetic diversity of the Denisovans themselves was extremely low.

“By doing some more sophisticated analysis, one could actually track back the genetic diversity through time, and it became apparent that the genetic diversity was low over the last few hundred thousand years of the Denisovan history,” said Matthias Meyer of the Max Planck Institute for Evolutionary Anthropology.

Given the Denisovans’ wide geographic range over time, it’s likely that their population was initially quite small but grew quickly, without time for genetic diversity to increase.

If further research shows that the Neandertal population size changed over time in a similar way, that may suggest that a single population expanding out of Africa gave rise to both the Denisovans and Neandertals, the study authors say.

Read the abstract, “A High-Coverage Genome Sequence From an Archaic Denisovan Individual,” by Matthias Meyer and colleagues.



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