75,000-year-old female Neanderthal from cave where species buried their dead

A new documentary has recreated the face of a 75,000-year-old female Neanderthal whose flattened skull was discovered and rebuilt from hundreds of bone fragments by a team of archaeologists and conservators led by the University of Cambridge.

The team excavated the female Neanderthal in 2018 from inside a cave in Iraqi Kurdistan where the species had repeatedly returned to lay their dead to rest. The cave was made famous by work in the late 1950s that unearthed several Neanderthals which appeared to have been buried in succession.

'Secrets of the Neanderthals', produced by BBC Studios Science Unit, is released on Netflix worldwide. The documentary follows the team led by the universities of Cambridge and Liverpool John Moores as they return to Shanidar Cave to continue excavations.

"The skulls of Neanderthals and humans look very different," said Dr Emma Pomeroy, a palaeo-anthropologist from Cambridge's Department of Archaeology, who features in the new film.

"Neanderthal skulls have huge brow ridges and lack chins, with a projecting midface that results in more prominent noses. But the recreated face suggests those differences were not so stark in life.

"It's perhaps easier to see how interbreeding occurred between our species, to the extent that almost everyone alive today still has Neanderthal DNA."

Neanderthals are thought to have died out around 40,000 years ago, and the discoveries of new remains are few and far between. The Neanderthal featured in the documentary is the first from the cave for over fifty years, and perhaps the best preserved individual to be found this century.

While earlier finds were numbered, this one is called Shanidar Z, although researchers think it may be the top half of an individual excavated in 1960.

The head had been crushed, possibly by rockfall, relatively soon after death -- after the brain decomposed but before the cranium filled with dirt -- and then compacted further by tens of thousands of years of sediment.

When archaeologists found it, the skull was flattened to around two centimetres thick.

The team carefully exposed the remains, including an articulated skeleton almost to the waist, and used a glue-like consolidant to strengthen the bones and surrounding sediment. They removed Shanidar Z in dozens of small foil-wrapped blocks from under seven and a half metres of soil and rock within the heart of the cave.

In the Cambridge lab, researchers took micro-CT scans of each block before gradually diluting the glue and using the scans to guide extraction of bone fragments. Lead conservator Dr Lucía López-Polín pieced over 200 bits of skull together freehand to return it to its original shape, including upper and lower jaws.

"Each skull fragment is gently cleaned while glue and consolidant are re-added to stabilise the bone, which can be very soft, similar in consistency to a biscuit dunked in tea," said Pomeroy. "It's like a high stakes 3D jigsaw puzzle. A single block can take over a fortnight to process."

The team even referred to forensic science -- studies on how bones shift after blunt force trauma and during decomposition -- to help them understand if remains had been buried, and the ways in which teeth had pinged from jawbones.

The rebuilt skull was surface scanned and 3D-printed, forming the basis of a reconstructed head created by world-leading palaeoartists and identical twins Adrie and Alfons Kennis, who built up layers of fabricated muscle and skin to reveal a face.

New analysis strongly suggests that Shanidar Z was an older female, perhaps in her mid-forties according to researchers -- a significant age to reach so deep in prehistory.

Without pelvic bones, the team relied on sequencing tooth enamel proteins to determine her sex. Teeth were also used to gauge her age through levels of wear and tear -- with some front teeth worn down to the root. At around five feet tall, and with some of the smallest adult arm bones in the Neanderthal fossil record, her physique also implies a female.

While remnants of at least ten separate Neanderthals have now come from the cave, Shanidar Z is the fifth to be found in a cluster of bodies buried at a similar time in the same location: right behind a huge vertical rock, over two metres tall at the time, which sits in the centre of the cave.

The rock had come down from the ceiling long before the bodies were interred. Researchers say it may have served as a landmark for Neanderthals to identify a particular site for repeated burials.

"Neanderthals have had a bad press ever since the first ones were found over 150 years ago," said Professor Graeme Barker from Cambridge's McDonald Institute for Archaeological Research, who leads the excavations at the cave.

"Our discoveries show that the Shanidar Neanderthals may have been thinking about death and its aftermath in ways not so very different from their closest evolutionary cousins -- ourselves."

The other four bodies in the cluster were discovered by archaeologist Ralph Solecki in 1960. One was surrounded by clumps of ancient pollen. Solecki and pollen specialist Arlette Leroi-Gourhan argued the finds were evidence of funerary rituals where the deceased was laid to rest on a bed of flowers.

This archaeological work was among the first to suggest Neanderthals were far more sophisticated than the primitive creatures many had assumed, based on their stocky frames and ape-like brows.

Decades later, the Cambridge-led team retraced Solecki's dig, aiming to use the latest techniques to retrieve more evidence for his contentious claims, as well as the environment and activities of the Neanderthals and later modern humans who lived there, when they uncovered Shanidar Z.

"Shanidar Cave was used first by Neanderthals and then by our own species, so it provides an ideal laboratory to tackle one of the biggest questions of human evolution," said Barker.

"Why did Neanderthals disappear from the stage around the same time as Homo sapiens spread over regions where Neanderthals had lived successfully for almost half a million years?"

A study led by Professor Chris Hunt of Liverpool John Moores University now suggests the pollen was left by bees burrowing into the cave floor. However, remains from Shanidar Cave still show signs of an empathetic species. For example, one male had a paralysed arm, deafness and head trauma that likely rendered him partially blind, yet had lived a long time, so must have been cared for.

Site analysis suggests that Shanidar Z was laid to rest in a gully formed by running water that had been further hollowed out by hand to accommodate the body. Posture indicates she had been leant against the side, with her left hand curled under her head, and a rock behind the head like a small cushion, which may have been placed there.

While Shanidar Z was buried within a similar timeframe as other bodies in the cluster, researchers cannot say how contemporaneous they are, only that they all date to around 75,000 years ago.

In fact, while filming onsite for the new documentary in 2022, the team found remains of yet another individual in the same burial cluster, uncovering the left shoulder blade, some ribs and a fairly complete right hand.

In the sediments several feet above, another three Neanderthals dating to around 50,000 years had been found by Solecki, more of which have been recovered by the current team.

Further research since Shanidar Z was found has detected microscopic traces of charred food in the soil around the older body cluster. These carbonised bits of wild seeds, nuts and grasses, suggest not only that Neanderthals prepared food -- soaking and pounding pulses -- and then cooked it, but did so in the presence of their dead.

"The body of Shanidar Z was within arm's reach of living individuals cooking with fire and eating," said Pomeroy. "For these Neanderthals, there does not appear to be that clear separation between life and death."

"We can see that Neanderthals are coming back to one particular spot to bury their dead. This could be decades or even thousands of years apart. Is it just a coincidence, or is it intentional, and if so what brings them back?"

Read more at Science Daily

Did neanderthals use glue? Researchers find evidence that sticks

Neanderthals created stone tools held together by a multi-component adhesive, a team of scientists has discovered. Its findings, which are the earliest evidence of a complex adhesive in Europe, suggest these predecessors to modern humans had a higher level of cognition and cultural development than previously thought.

The work, reported in the journal Science Advances, included researchers from New York University, the University of Tübingen, and the National Museums in Berlin.

"These astonishingly well-preserved tools showcase a technical solution broadly similar to examples of tools made by early modern humans in Africa, but the exact recipe reflects a Neanderthal 'spin,' which is the production of grips for handheld tools," says Radu Iovita, an associate professor at New York University's Center for the Study of Human Origins.

The research team, led by Patrick Schmidt from the University of Tübingen's Early Prehistory and Quaternary Ecology section and Ewa Dutkiewicz from the Museum of Prehistory and Early History at the National Museums in Berlin, re-examined previous finds from Le Moustier, an archaeological site in France that was discovered in the early 20th century.

The stone tools from Le Moustier -- used by Neanderthals during the Middle Palaeolithic period of the Mousterian between 120,000 and 40,000 years ago -- are kept in the collection of Berlin's Museum of Prehistory and Early History and had not previously been examined in detail.

The tools were rediscovered during an internal review of the collection and their scientific value was recognized.

"The items had been individually wrapped and untouched since the 1960s," says Dutkiewicz.

"As a result, the adhering remains of organic substances were very well preserved."

The researchers discovered traces of a mixture of ochre and bitumen on several stone tools, such as scrapers, flakes, and blades.

Ochre is a naturally occurring earth pigment; bitumen is a component of asphalt and can be produced from crude oil, but also occurs naturally in the soil.

"We were surprised that the ochre content was more than 50 percent," says Schmidt.

"This is because air-dried bitumen can be used unaltered as an adhesive, but loses its adhesive properties when such large proportions of ochre are added."

He and his team examined these materials in tensile tests -- used to determine strength -- and other measures.

"It was different when we used liquid bitumen, which is not really suitable for gluing. If 55 percent ochre is added, a malleable mass is formed," Schmidt says.

The mixture was just sticky enough for a stone tool to remain stuck in it, but without adhering to hands, making it suitable material for a handle.

In fact, a microscopic examination of the use-wear traces on these stone tools revealed that the adhesives on the tools from Le Moustier were used in this way.

"The tools showed two kinds of microscopic wear: one is the typical polish on the sharp edges that is generally caused by working other materials," explains Iovita, who conducted this analysis.

"The other is a bright polish distributed all over the presumed hand-held part, but not elsewhere, which we interpreted as the results of abrasion from the ochre due to movement of the tool within the grip."

The use of adhesives with several components, including various sticky substances such as tree resins and ochre, was previously known from early modern humans, Homo sapiens, in Africa but not from earlier Neanderthals in Europe.

Overall, the development of adhesives and their use in the manufacture of tools is considered to be some of the best material evidence of the cultural evolution and cognitive abilities of early humans.

"Compound adhesives are considered to be among the first expressions of the modern cognitive processes that are still active today," says Schmidt.

In the Le Moustier region, ochre and bitumen had to be collected from distant locations, which meant a great deal of effort, planning, and a targeted approach, the authors note.

"Taking into account the overall context of the finds, we assume that this adhesive material was made by Neanderthals," concludes Dutkiewicz.

"What our study shows is that early Homo sapiens in Africa and Neanderthals in Europe had similar thought patterns," adds Schmidt.

Read more at Science Daily

Neanderthals and humans lived side by side in Northern Europe 45,000 years ago

A genetic analysis of bone fragments unearthed at an archaeological site in central Germany shows conclusively that modern humans -- Homo sapiens -- had already reached Northern Europe 45,000 years ago, overlapping with Neanderthals for several thousand years before the latter went extinct.

The findings establish that the site near Ranis, Germany, which is known for its finely flaked, leaf-shaped stone tool blades, is among the oldest confirmed sites of modern human Stone Age culture in north central and northwestern Europe.

The evidence that Homo sapiens and Homo neanderthalensis lived side by side is consistent with genomic evidence that the two species occasionally interbred. It also feeds the suspicion that the invasion of Europe and Asia by modern humans some 50,000 years ago helped drive Neanderthals, which had occupied the area for more than 500,000 years, to extinction.

The genetic analysis, along with an archaeological and isotopic analysis and radiocarbon dating of the Ranis site, are detailed in a trio of papers appearing today in the journals Nature and Nature Ecology and Evolution.

The stone blades at Ranis, referred to as leaf points, are similar to stone tools found at several sites in Moravia, Poland, Germany and the United Kingdom. These tools that are thought to have been produced by the same culture, referred to as the Lincombian-Ranisian-Jerzmanowician (LRJ) culture or technocomplex. Because of previous dating, the Ranis site was known to be 40,000 years old or older, but without recognizable bones to indicate who made the tools, it was unclear whether they were the product of Neanderthals or Homo sapiens.

The new findings demonstrate that "Homo sapiens made this technology, and that Homo sapiens were this far north at this time period, which is 45,000 years ago," said Elena Zavala, one of four first authors of the Nature paper and a Miller Research Fellow at the University of California, Berkeley. "So these are among the earliest Homo sapiens in Europe."

Zavala was a Ph.D. student at the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) in Leipzig in 2018 when she first began working on the project, which was a major effort spearheaded by Jean-Jacque Hublin, former director of the institute and a professor at the Collège de France in Paris.

"The Ranis cave site provides evidence for the first dispersal of Homo sapiens across the higher latitudes of Europe. It turns out that stone artifacts that were thought to be produced by Neanderthals were, in fact, part of the early Homo sapiens toolkit," Hublin said. "This fundamentally changes our previous knowledge about the period: Homo sapiens reached northwestern Europe long before Neanderthal disappearance in southwestern Europe."

Bones from maternal relatives?

Zavala conducted the genetic analysis of hominid bone fragments from the new and deeper excavations at Ranis between 2016 and 2022 and from earlier excavations in the 1930s. Because the DNA in ancient bones is highly fragmented, she employed special techniques to isolate and sequence the DNA, all of it mitochondrial DNA (mtDNA) that is inherited solely from the mother.

"We confirmed that the skeletal fragments belonged to Homo sapiens. Interestingly, several fragments shared the same mitochondrial DNA sequences -- even fragments from different excavations," she said. "This indicates that the fragments belonged to the same individual or their maternal relatives, linking these new finds with the ones from decades ago."

The bone fragments were initially identified as human through analysis of bone proteins -- a field called paleoproteomics -- by another first author, Dorothea Mylopotamitaki, a doctoral student at the Collège de France and fomerly of MPI-EVA.

By comparing the Ranis mitochondrial DNA sequences with mtDNA sequences obtained from human remains at other paleolithic sites in Europe, Zavala was able to construct a family tree of early Homo sapiens across Europe. All but one of the 13 Ranis fragments were quite similar to one another and, surprisingly, resembled mtDNA from the 43,000-year-old skull of a woman discovered in a cave at Zlatý k?? in the Czech Republic. The lone standout grouped with an individual from Italy.

"That raises some questions: Was this a single population? What could be the relationship here?" Zavala said. "But with mitochondrial DNA, that's only one side of the history. It's only the maternal side. We would need to have nuclear DNA to be able to start looking into this."

A transitional site between Middle and Upper Paleolithic

Zavala specializes in the analysis of DNA found in long-buried bones, on bone tools and in sediment. Her search through sediment from various levels of the Ranis excavation turned up DNA from a broad array of mammals, but none from hominids. The analysis, combined with morphological, isotopic and proteomic analysis of bone fragments, paints a picture of the environment at that time and of the diet of both humans and animals that occupied the cave over the millennia.

The presence of reindeer, cave bear, woolly rhinoceros and horse bones, for example, indicated cold climatic conditions typical of steppe tundra and similar to conditions in Siberia and northern Scandinavia today, and a human diet based on large terrestrial animals. The researchers concluded that the cave was used primarily by hibernating cave bears and denning hyenas, with only periodic human presence.

"This lower-density archaeological signature matches other Lincombian-Ranisian-Jerzmanowician sites and is best explained by expedient visits of short duration by small, mobile groups of pioneer H. sapiens," according to one of the papers published in Nature Ecology and Evolution.

"This shows that even these earlier groups of Homo sapiens dispersing across Eurasia already had some capacity to adapt to such harsh climatic conditions," said Sarah Pederzani, a postdoctoral fellow at the University of La Laguna in Spain, who led the paleoclimate study of the site. "Until recently, it was thought that resilience to cold-climate conditions did not appear until several thousand years later, so this is a fascinating and surprising result."

The Ranis site, called Ilsenhöhle and located at the base of a castle, was initially excavated mainly between 1932 and 1938. The leaf points found there were eventually assigned to the final years of the Middle Paleolithic period -- between about 300,000 and 30,000 years ago -- or the beginning of the Upper Paleolithic, which begins around 50,000 years ago.

Because of the importance of the Ranis site for understanding the LRJ technocomplex and the transition from the Neanderthal-associated late Middle Paleolithic to the modern human Upper Paleolithic in central Europe, Hublin and his team decided to reexcavate the site using modern tools of archaeology.

The new excavations extended to bedrock, about 8 meters below the surface, and involved removing a rock -- likely fallen from the cave ceiling -- that had halted the previous excavation. Here, Hublin's team uncovered chips from flint tools and a quartzite flake consistent with the LRJ technocomplex. Subsequent proteomic analysis of thousands of recovered bone chips confirmed that four were from hominids. Of bone chips uncovered during the 1930s excavations, nine were from hominids.

Zavala's DNA analysis confirmed that all 13 bone fragments came from Homo sapiens.

A revised settlement history of Northern Europe

The team also carried out radiocarbon dating of human and animal bones from different layers of the site to reconstruct the site's chronology, focusing on bones with traces of human modifications on their surfaces, which links their dates to human presence in the cave.

"We found very good agreement between the radiocarbon dates from the Homo sapiens bones from both excavation collections and with modified animal bones from the LRJ layers of the new excavation, making a very strong link between the human remains and LRJ. The evidence suggests that Homo sapiens were sporadically occupying the site from as early as 47,500 years ago," said another first author, Helen Fewlass, a former Max Planck researcher who is now a European Molecular Biology Organization (EMBO) Postdoctoral Fellow at the Francis Crick Institute in London.

"The results from the Ilsenhöhle in Ranis fundamentally changed our ideas about the chronology and settlement history of Europe north of the Alps," added Tim Schüler of the Thuringian State Office for the Preservation of Historical Monuments and Archaeology in Weimar, Germany.

Read more at Science Daily

Neanderthals were the world's first artists, research reveals

Recent research has shown that engravings in a cave in La Roche-Cotard (France), which has been sealed for thousands of years, were actually made by Neanderthals. This research was performed by Basel archaeologist Dorota Wojtczak together with a team of researchers from France and Denmark, whose findings reveal that the Neanderthals were in fact the first humans with an appreciation of art.

When the French archaeologist Jean-Claude Marquet entered the La Roche-Cotard cave in the Loire Valley for the first time back in 1974, he suspected that the fine lines on the wall could be of human origin.

He also found scrapers and other retouched pieces known as Mousterian stone artifacts that suggested the cave had been used by Neanderthals.

Were the marks on the wall evidence of early Neanderthal artistic activity?

Posing this question raised the possibility of breaking with the consensus of the time, which largely assumed that Homo neanderthalensis lacked any higher cognitive abilities.

Fearing he would be unable to provide sufficient scientific evidence to prove his hypothesis, Marquet left the cave untouched for almost 40 years.

Marks on the wall produced by human hands

Together with an international team, he made another attempt in 2016.

This time he was accompanied by Dr. Dorota Wojtczak from Integrative Prehistoric and Archaeological Science (IPAS) at the Department of Environmental Sciences of the University of Basel, who specializes in archaeological use-wear analysis.

"Our task was to use modern methods to prove the human origin of these wall engravings," explains Wojtczak in her office at IPAS.

The researchers recently published their findings in the journal PLoS ONE.

First with photos and drawings and later with a 3D scanner, the marks in the tuff rock of the cave wall were meticulously recorded.

In her laboratory in Basel, Wojtczak compared these samples from the cave with tuff she had worked on experimentally with wood, bone and stone tools, as well as with her hands.

"This research clearly showed that the cave marks were not made with tools, but by scratching with human fingers," says Wojtczak.

Cave sealed for over 50,000 years

At the same time, examination of cave sediment by researchers from Denmark showed that the cave must have been sealed off by mud residues from the Loire and soil sediments for over 50,000 years before being rediscovered.

This makes the La Roche-Cotard cave system a very special location -- a veritable "time capsule." "At this time, 50,000 years ago, there were no modern humans in Europe, only Neanderthals," says Wojtczak.

The wall marks and artifacts can therefore only come from these early humans.

While the clear geometric shapes with parallel and triangular lines suggest that these marks were not scribbled on the wall by chance, the researcher does not know what they represent.

"But they could only have been made by someone who proceeded with planning and understanding," she says.

And whether it was "art" as such, or a form of recording-keeping, is a matter of interpretation.

La Roche-Cotard promises further findings

The cave holds many other archaeological secrets. Jean-Claude Marquet also found an object that resembles the face of a human or animal back in 1976, and Wojtczak's use-wear analysis suggests that this object is also man-made.

Another object from the cave appears to be a small oil lamp.

"Specialists are currently investigating whether the object bears any pigments or soot substances that could help to identify the type of fuel used at the time," explains Wojtczak.

The chamber of La Roche-Cotard that has been explored so far is just one part of an entire cave system.

The researcher hopes to gain further insight into the Neanderthals' activities, particularly from Chamber 4, which is still largely covered by sediment.

Wojtczak is convinced that every investigation will help to further the dismantle traditional consensus of Neanderthals as mentally inferior humans, and reinforce the perception of them as more like the cousins of modern humans.

Read more at Science Daily

Neanderthal gene variants associated with greater pain sensitivity

People who carry three gene variants that have bene inherited from Neanderthals are more sensitive to some types of pain, according to a new study co-led by UCL researchers.

The findings, published in Communications Biology, are the latest findings to show how past interbreeding with Neanderthals has influenced the genetics of modern humans.

The researchers found that people carrying three so-called Neanderthal variants in the gene SCN9A, which is implicated in sensory neurons, are more sensitive to pain from skin pricking after prior exposure to mustard oil.

Previous research has identified three variations in the SCN9A gene -- known as M932L, V991L, and D1908G -- in sequenced Neanderthal genomes and reports of greater pain sensitivity among humans carrying all three variants. However, prior to this study the specific sensory responses affected by these variants was unclear.

An international team led by researchers at UCL, Aix-Marseille University, University of Toulouse, Open University, Fudan University, and Oxford University, and part-funded by Wellcome, measured the pain thresholds of 1,963 people from Colombia in response to a range of stimuli.

The SCN9A gene encodes a sodium channel that is expressed at high levels in sensory neurons that detect signals from damaged tissue. The researchers found that the D1908G variant of the gene was present in around 20% of chromosomes within this population and around 30% of chromosomes carrying this variant also carried the M932L and V991L variants.

The authors found that the three variants were associated with a lower pain threshold in response to skin pricking after prior exposure to mustard oil, but not in response to heat or pressure. Additionally, carrying all three variants was associated with greater pain sensitivity than carrying only one.

When they analysed the genomic region including SCN9A using genetic data from 5,971 people from Brazil, Chile, Colombia, Mexico and Peru, the authors found that the three Neanderthal variants were more common in populations with higher proportions of Native American ancestry, such as the Peruvian population, in which the average proportion of Native American ancestry was 66%.

The authors propose that the Neanderthal variants may sensitise sensory neurons by altering the threshold at which a nerve impulse is generated. They speculate that the variants may be more common in populations with higher proportions of Native American ancestry as a result of random chance and population bottlenecks that occurred during the initial occupation of the Americas. Although acute pain can moderate behaviour and prevent further injury, the scientists that say additional research is needed to determine whether carrying these variants and having greater pain sensitivity may have been advantageous during human evolution.

Previous research by co-corresponding author Dr Kaustubh Adhikari (UCL Genetics, Evolution & Environment and The Open University) has shown that humans also inherited some genetic material from Neanderthals affecting the shape of our noses.*

Dr Adhikari commented: "In the last 15 years, since the Neanderthal genome was first sequenced, we have been learning more and more about what we have inherited from them as a result of interbreeding tens of thousands of years ago.

"Pain sensitivity is an important survival trait that enables us to avoid painful things that could cause us serious harm. Our findings suggest that Neanderthals may have been more sensitive to certain types of pain, but further research is needed for us to understand why that is the case, and whether these specific genetic variants were evolutionarily advantageous."

Read more at Science Daily

The Viking disease can be due to gene variants inherited from Neanderthals

Many men in northern Europe over the age of 60 suffer from the so-called Viking disease, which means that the fingers lock in a bent position. Now researchers at Karolinska Institutet, together with colleagues, have used data from over 7,000 affected individuals to look for genetic risk factors for the disease. The findings, which have been published in Molecular Biology and Evolution, show that three of the strongest risk factors are inherited from Neanderthals.

Up to 30 percent of men in northern Europe over 60 suffer from a condition called Dupuytren's contracture. The condition is sometimes called the Viking disease because it mainly affects individuals with northern European ancestry. The disease is significantly more common in men than women and usually begins as a lump in the palm of the hand that grows and causes one or more fingers to lock in a bent position. The condition is usually not painful, but the nodules may sometimes be tender to pressure.

The researchers in the study, led by Hugo Zeberg from Karolinska Institutet and Svante Pääbo from Max Planck Institute for Evolutionary Anthropology, set out to investigate whether genetic variants inherited from Neanderthals are involved in the disease.

Neanderthals lived in Europe and western Asia until about 40,000 years ago, when they were replaced by modern humans. However before Neanderthals disappeared, they mixed with modern humans. As a result, between one and two percent of the genomes of people with roots outside of Africa come from Neanderthals.

"Since Dupuytren's contracture is rarely seen in individuals of African descent, we wondered whether gene variants from Neanderthals can partly explain why people outside of Africa are affected," says Hugo Zeberg, assistant professor at the department of Physiology and Pharmacology, Karolinska Institutet.

The researchers used data from three large clinical cohorts in the US, UK, and Finland, which allowed them to compare the genomes of 7,871 sufferers and 645,880 healthy controls. They identified 61 genetic risk factors for Dupuytren's contracture. The researchers found that three of these were inherited from Neanderthals, and these included the second and third most important risk factors.

The study is further evidence that the intermingling between Neanderthals and our ancestors has important consequences for the prevalence of some diseases, particularly among certain groups.

"This is a case where the meeting with Neanderthals has affected who suffers from illness, although we should not exaggerate the connection between Neanderthals and Vikings," says Hugo Zeberg.

Read more at Science Daily

Lingering effects of Neanderthal DNA found in modern humans

Recent scientific discoveries have shown that Neanderthal genes comprise some 1 to 4% of the genome of present-day humans whose ancestors migrated out of Africa, but the question remained open on how much those genes are still actively influencing human traits -- until now.

A multi-institution research team including Cornell University has developed a new suite of computational genetic tools to address the genetic effects of interbreeding between humans of non-African ancestry and Neanderthals that took place some 50,000 years ago. (The study applies only to descendants of those who migrated from Africa before Neanderthals died out, and in particular, those of European ancestry.)

In a study published in eLife, the researchers reported that some Neanderthal genes are responsible for certain traits in modern humans, including several with a significant influence on the immune system. Overall, however, the study shows that modern human genes are winning out over successive generations.

"Interestingly, we found that several of the identified genes involved in modern human immune, metabolic and developmental systems might have influenced human evolution after the ancestors' migration out of Africa," said study co-lead author April (Xinzhu) Wei, an assistant professor of computational biology in the College of Arts and Sciences. "We have made our custom software available for free download and use by anyone interested in further research."

Using a vast dataset from the UK Biobank consisting of genetic and trait information of nearly 300,000 Brits of non-African ancestry, the researchers analyzed more than 235,000 genetic variants likely to have originated from Neanderthals. They found that 4,303 of those differences in DNA are playing a substantial role in modern humans and influencing 47 distinct genetic traits, such as how fast someone can burn calories or a person's natural immune resistance to certain diseases.

Unlike previous studies that could not fully exclude genes from modern human variants, the new study leveraged more precise statistical methods to focus on the variants attributable to Neanderthal genes.

While the study used a dataset of almost exclusively white individuals living in the United Kingdom, the new computational methods developed by the team could offer a path forward in gleaning evolutionary insights from other large databases to delve deeper into archaic humans' genetic influences on modern humans.

"For scientists studying human evolution interested in understanding how interbreeding with archaic humans tens of thousands of years ago still shapes the biology of many present-day humans, this study can fill in some of those blanks," said senior investigator Sriram Sankararaman, an associate professor at the University of California, Los Angeles. "More broadly, our findings can also provide new insights for evolutionary biologists looking at how the echoes of these types of events may have both beneficial and detrimental consequences."

Read more at Science Daily

Tooth enamel provides clues to hunter-gatherer lifestyle of Neanderthals

A study by an international team of researchers, led by the University of Southampton, has given an intriguing glimpse of the hunting habits and diets of Neanderthals and other humans living in western Europe.

The scientists examined chemical properties locked inside tooth enamel to piece together how pre-historic people lived off the land around the Almonda Cave system, near Torres Novas in central Portugal almost 100 thousand years ago.

Their findings, published in the journal PNAS, show Neanderthals in the region were hunting fairly large animals across wide tracts of land, whereas humans living in the same location tens of thousands of years later survived on smaller creatures in an area half the size.

Strontium isotopes in rocks gradually change over millions of years because of radioactive processes. This means they vary from place to place depending on the age of the underlying geology. As rocks weather, the isotopic 'fingerprints' are passed into plants via sediments, and make their way along the food chain -- eventually passing into tooth enamel.

In this study, archaeologists used a technique which laser samples enamel and makes thousands of individual strontium isotope measurements along the growth of a tooth crown. Samples were taken from two Neanderthals, dating back about 95,000 years, and from a more recent human who lived about 13,000 years ago, during the Magdalenian period.

The scientists also looked at isotopes in the tooth enamel of animals found in the cave system. Alongside strontium, they measured oxygen isotopes, which vary seasonally from summer to winter. This enabled them to establish not only where the animals ranged across the landscape, but in which seasons they were available for hunting.

The team showed that the Neanderthals, who were targeting large animals, could have hunted wild goat in the summer, whereas horses, red deer and an extinct form of rhinoceros were available all year round within about 30km of the cave. The Magdalenian individual showed a different pattern of subsistence, with seasonal movement of about 20km from the Almonda caves to the banks of the Tagus River, and a diet which included rabbits, red deer, wild goat and freshwater fish.

The researchers approximated the territory of the two different human groups, revealing contrasting results. The Neanderthals obtained their food over approximately 600 km2, whereas the Magdalenian individuals occupied a much smaller territory of about 300 km2.

Lead author, Dr Bethan Linscott who conducted the research while at the University of Southampton and who now works at the University of Oxford said: "Tooth enamel forms incrementally, and so represents a time series that records the geological origin of the food an individual ate.

"Using laser ablation, we can measure the variation of strontium isotopes over the two or three years it takes for the enamel to form. By comparing the strontium isotopes in the teeth with sediments collected at different locations in the region, we were able to map the movements of the Neanderthals and the Magdalenian individual. The geology around the Almonda caves is highly variable, making it possible to spot movement of just a few kms."

Co-author, Professor Alistair Pike of the University of Southampton, who supervised the research said: "This study shows just how much science has changed our understanding of archaeology in the past decade. Previously, the lives and behaviours of past individuals was limited to what we could infer from marks on their bones or the artefacts they used. Now, using the chemistry of bones and teeth, we can begin to reconstruct individual life histories, even as far back as the Neanderthals."

Read more at Science Daily

Nose shape gene inherited from Neanderthals

Humans inherited genetic material from Neanderthals that affects the shape of our noses, finds a new study led by UCL researchers.

The new Communications Biology study finds that a particular gene, which leads to a taller nose (from top to bottom), may have been the product of natural selection as ancient humans adapted to colder climates after leaving Africa.

Co-corresponding author Dr Kaustubh Adhikari (UCL Genetics, Evolution & Environment and The Open University) said: "In the last 15 years, since the Neanderthal genome has been sequenced, we have been able to learn that our own ancestors apparently interbred with Neanderthals, leaving us with little bits of their DNA.

"Here, we find that some DNA inherited from Neanderthals influences the shape of our faces. This could have been helpful to our ancestors, as it has been passed down for thousands of generations."

The study used data from more than 6,000 volunteers across Latin America, of mixed European, Native American and African ancestry, who are part of the UCL-led CANDELA study, which recruited from Brazil, Colombia, Chile, Mexico and Peru. The researchers compared genetic information from the participants to photographs of their faces -- specifically looking at distances between points on their faces, such as the tip of the nose or the edge of the lips -- to see how different facial traits were associated with the presence of different genetic markers.

The researchers newly identified 33 genome regions associated with face shape, 26 of which they were able to replicate in comparisons with data from other ethnicities using participants in east Asia, Europe, or Africa.

In one genome region in particular, called ATF3, the researchers found that many people in their study with Native American ancestry (as well as others with east Asian ancestry from another cohort) had genetic material in this gene that was inherited from the Neanderthals, contributing to increased nasal height. They also found that this gene region has signs of natural selection, suggesting that it conferred an advantage for those carrying the genetic material.

First author Dr Qing Li (Fudan University) said: "It has long been speculated that the shape of our noses is determined by natural selection; as our noses can help us to regulate the temperature and humidity of the air we breathe in, different shaped noses may be better suited to different climates that our ancestors lived in. The gene we have identified here may have been inherited from Neanderthals to help humans adapt to colder climates as our ancestors moved out of Africa."

Co-corresponding author Professor Andres Ruiz-Linares (Fudan University, UCL Genetics, Evolution & Environment, and Aix-Marseille University) added: "Most genetic studies of human diversity have investigated the genes of Europeans; our study's diverse sample of Latin American participants broadens the reach of genetic study findings, helping us to better understand the genetics of all humans."

The finding is the second discovery of DNA from archaic humans, distinct from Homo sapiens, affecting our face shape. The same team discovered in a 2021 paper that a gene influencing lip shape was inherited from the ancient Denisovans.

Read more at Science Daily

Waxing and waning of environment influences hominin dispersals across ancient Iran

A world-first model of paleoclimate and hydrology in Iran has highlighted favourable routes for Neanderthals and modern human expansions eastwards into Asia.

Published in PLOS ONE, the findings reveal for the first time that multiple humid periods in ancient Iran led to the expansions of human populations, opening dispersal route across the region, and the possible interactions of species such as Neanderthals and our own Homo sapiens.

Professor Michael Petraglia, a key researcher in the study, said historic humid periods resulted in massive changes to ecosystems and led the team to identify large lakes in areas that were formerly deserts.

"Conversely, during glacial periods this increased aridity would have led to the expansion of deserts, led to contractions, and the isolation of hominin populations," said Professor Petraglia, who is the Director of Griffith's Australian Research Centre for Human Evolution.

"This cycle of wetting and drying is shown for the first time in Iran."

The research team, led by PhD candidate Mohammad Javad Shoaee from the Max Planck Institute for Geoanthropology in Germany, found that during Marine Isotope Stage (MIS) 5, a warm, humid period beginning roughly 130,000 years ago, lakes and rivers enabled two pathways for human groups.

One was a northern route through the Alborz and Kopet Dagh Mountains and north of the Dasht-I Kavir desert. The other route, first identified here, ran south along the Zagros Mountains before extending eastwards towards Pakistan and Afghanistan.

The researchers also found evidence for a potential northern route during MIS 3, beginning about 57,000 years ago, which, given artifacts attributed to multiple tool making groups, could have permitted interactions between modern humans and Neanderthals.

"These findings highlight the importance of Iran for our species' dispersals out of Africa and ultimately around the globe," said Professor Petraglia.

"As in other regions long considered too arid for early human occupations, such as the Arabian Peninsula, recent palaeoclimatic research is changing how we understand the human story and the role that changing climates have played."

"We recognised a new southern route along the Zagros Mountains and extending eastwards towards Pakistan and Afghanistan. We found evidence for a potential northern route during MIS 3, which would have permitted hominin movements and species interactions in Southwest Asia," Shoaee said.

To find out how human groups made their way into Iran, the team developed the first spatially comprehensive, high resolution palaeohydrological model for Iran.

They then compared their model, which showed when and where water was available, to the distribution of previously documented archaeological sites.

The result was a clear relationship between the availability of water and the evidence of human presence.

Not only does the current study help to explain the presence of previously documented sites, it also serves as a guide for future archaeological surveys in the region.

"Our paleohydrological analyses identified 145,354km of rivers and 115 paleolakes calculated from 6380 paleolake deposits. Only a handful of these paleolakes have so far been studied," Shoaee said.

Read more at Science Daily

Human evolution wasn't just the sheet music, but how it was played

A team of Duke researchers has identified a group of human DNA sequences driving changes in brain development, digestion and immunity that seem to have evolved rapidly after our family line split from that of the chimpanzees, but before we split with the Neanderthals.

Our brains are bigger, and are guts are shorter than our ape peers.

"A lot of the traits that we think of as uniquely human, and human-specific, probably appear during that time period," in the 7.5 million years since the split with the common ancestor we share with the chimpanzee, said Craig Lowe, Ph.D., an assistant professor of molecular genetics and microbiology in the Duke School of Medicine.

Specifically, the DNA sequences in question, which the researchers have dubbed Human Ancestor Quickly Evolved Regions (HAQERS), pronounced like hackers, regulate genes. They are the switches that tell nearby genes when to turn on and off. The findings appear Nov.23 in the journal Cell.

The rapid evolution of these regions of the genome seems to have served as a fine-tuning of regulatory control, Lowe said. More switches were added to the human operating system as sequences developed into regulatory regions, and they were more finely tuned to adapt to environmental or developmental cues. By and large, those changes were advantageous to our species.

"They seem especially specific in causing genes to turn on, we think just in certain cell types at certain times of development, or even genes that turn on when the environment changes in some way," Lowe said.

A lot of this genomic innovation was found in brain development and the GI tract. "We see lots of regulatory elements that are turning on in these tissues," Lowe said. "These are the tissues where humans are refining which genes are expressed and at what level."

Today, our brains are larger than other apes, and our guts are shorter. "People have hypothesized that those two are even linked, because they are two really expensive metabolic tissues to have around," Lowe said. "I think what we're seeing is that there wasn't really one mutation that gave you a large brain and one mutation that really struck the gut, it was probably many of these small changes over time."

To produce the new findings, Lowe's lab collaborated with Duke colleagues Tim Reddy, an associate professor of biostatistics and bioinformatics, and Debra Silver, an associate professor of molecular genetics and microbiology to tap their expertise. Reddy's lab is capable of looking at millions of genetic switches at once and Silver is watching switches in action in developing mouse brains.

"Our contribution was, if we could bring both of those technologies together, then we could look at hundreds of switches in this sort of complex developing tissue, which you can't really get from a cell line," Lowe said.

"We wanted to identify switches that were totally new in humans," Lowe said. Computationally, they were able to infer what the human-chimp ancestor's DNA would have been like, as well as the extinct Neanderthal and Denisovan lineages. The researchers were able to compare the genome sequences of these other post-chimpanzee relatives thanks to databases created from the pioneering work of 2022 Nobel laureate Svante Pääbo.

"So, we know the Neanderthal sequence, but let's test that Neanderthal sequence and see if it can really turn on genes or not," which they did dozens of times.

"And we showed that, whoa, this really is a switch that turns on and off genes," Lowe said. "It was really fun to see that new gene regulation came from totally new switches, rather than just sort of rewiring switches that already existed."

Along with the positive traits that HAQERs gave humans, they can also be implicated in some diseases.

Most of us have remarkably similar HAQER sequences, but there are some variances, "and we were able to show that those variants tend to correlate with certain diseases," Lowe said, namely hypertension, neuroblastoma, unipolar depression, bipolar depression and schizophrenia. The mechanisms of action aren't known yet, and more research will have to be done in these areas, Lowe said.

"Maybe human-specific diseases or human-specific susceptibilities to these diseases are going to be preferentially mapped back to these new genetic switches that only exist in humans," Lowe said.

Read more at Science Daily

Neanderthals appear to have been carnivores

For the first time, zinc isotope ratios in tooth enamel have been analysed with the aim of identifying the diet of a Neanderthal. The Neanderthal to whom the tooth belonged was probably a carnivore. Other chemical tracers indicate that this individual did not consume the blood of their prey, but ate the bone marrow without consuming the bones.

A new study published on October 17th in the journal PNAS, led by a CNRS researcher, has for the first time used zinc isotope analysis to determine the position of Neanderthals in the food chain. Their findings suggest that they were in fact carnivores.

Were Neanderthals carnivores? Scientists have not yet settled the question. While some studies of the dental tartar of individuals from the Iberian Peninsula appear to show that they were major consumers of plants, other research carried out at sites outside Iberia seem to suggest that they consumed almost nothing but meat. Using new analytical techniques on a molar belonging to an individual of this species, researchers1 have shown that the Neanderthals at the Gabasa site in Spain appear to have been carnivores.

To determine an individual's position in the food chain, scientists have until now generally had to extract proteins and analyse the nitrogen isotopes present in the bone collagen. However, this method can often only be used in temperate environments, and only rarely on samples over 50,000 years old. When these conditions are not met, nitrogen isotope analysis is very complex, or even impossible. This was the case for the molar from the Gabasa site analysed in this study.

Given these constraints, Klevia Jaouen, a CNRS researcher, and her colleagues decided to analyse the zinc isotope ratios present in the tooth enamel, a mineral that is resistant to all forms of degradation. This is the first time this method has been used to attempt to identify a Neanderthal's diet. The lower the proportions of zinc isotopes in the bones, the more likely they are to belong to a carnivore. The analysis was also carried out on the bones of animals from the same time period and geographical area, including carnivores such as lynxes and wolves, and herbivores like rabbits and chamois. The results showed that the Neanderthal to whom this tooth from the Gabasa site belonged was probably a carnivore who did not consume the blood of their prey.

Broken bones found at the site, together with isotopic data, indicate that this individual also ate the bone marrow of their prey, without consuming the bones, while other chemical tracers show that they were weaned before the age of two. Analyses also show that this Neanderthal probably died in the same place they had lived in as a child.

Compared to previous techniques, this new zinc isotope analysis method makes it easier to distinguish between omnivores and carnivores. To confirm their conclusions, the scientists hope to repeat the experiment on individuals from other sites, especially from the Payre site in south-east France, where new research is under way.

Read more at Science Daily

Meet the first Neanderthal family

For the first time, an international team led by researchers from the Max Planck Institute for Evolutionary Anthropology have managed to sequence multiple individuals from a remote Neandertal community in Siberia. Among these thirteen individuals, the researchers identified multiple related individuals -- among these a father and his teenage daughter. The researchers were also able to use the thirteen genomes to provide a glimpse into the social organization of a Neandertal community. They appear to have been a small group of close relatives, consisting of ten to twenty members, and communities were primarily connected through female migration.

The first Neanderthal draft genome was published in 2010. Since then, researchers from the Max Planck Institute for Evolutionary Anthropology have sequenced a further 18 genomes from 14 different archaeological sites throughout Eurasia. While these genomes have provided insights into the broader strokes of Neanderthal history, we still know little of individual Neanderthal communities.

To explore the social structure of Neanderthals, the researchers turned their attention to southern Siberia, a region that has previously been very fruitful for ancient DNA research -- including the discovery of Denisovan hominin remains at the famous Denisova Cave. From work done at that site, we know that Neanderthals and Denisovans were present in this region over hundreds of thousands of years, and that Neanderthals and Denisovans have interacted with each other -- as the finding of a child with a Denisovan father and a Neanderthal mother has shown.

First Neanderthal community

In their new study, the researchers focused on the Neanderthal remains in Chagyrskaya and Okladnikov Caves, which are within 100 kilometers of Denisova Cave. Neanderthals briefly occupied these sites around 54,000 years ago, and multiple potentially contemporaneous Neanderthal remains had been recovered from their deposits. The researchers successfully retrieved DNA from 17 Neanderthal remains -- the largest number of Neanderthal remains ever sequenced in a single study.

Chagyrskaya Cave has been excavated over the last 14 years by researchers from the Institute of Archaeology and Ethnography, Russian Academy of Sciences. Besides several hundred thousand stone tools and animal bones, they also recovered more than 80 bone and tooth fragments of Neanderthals, one of the largest assemblages of these fossil humans not only in the region but also in the world.

The Neanderthals at Chagyrskaya and Okladnikov hunted ibex, horses, bison and other animals that migrated through the river valleys that the caves overlook. They collected raw materials for their stone tools dozens of kilometers away, and the occurrence of the same raw material at both Chagyrskaya and Okladnikov Caves also supports the genetic data that the groups inhabiting these localities were closely linked.

Previous studies of a fossil toe from Denisova cave showed that Neanderthals inhabited the Altai mountains considerably earlier as well, around 120,000 years ago. Genetic data shows though, that the Neanderthals from Chagyrskaya and Okladnikov Caves are not descendants of these earlier groups, but are closer related to European Neanderthals. This is also supported by the archaeological material: the stone tools from Chagyrskaya Cave are most similar to the so-called Micoquian culture known from Germany and Eastern Europe.

The 17 remains came from 13 Neanderthal individuals -- 7 men and 6 women, of which 8 were adults and 5 were children and young adolescents. In their mitochondrial DNA, the researchers found several so-called heteroplasmies that were shared between individuals. Heteroplasmies are a special kind of genetic variant that only persists for a small number of generations.

The easternmost Neanderthals

Among these remains were those of a Neanderthal father and his teenage daughter. The researchers also found a pair of second degree relatives: a young boy and an adult female, perhaps a cousin, aunt or grandmother. The combination of heteroplasmies and related individuals strongly suggests that the Neanderthals in Chagyrskaya Cave must have lived -- and died -- at around the same time.

"The fact that they were living at the same time is very exciting. This means that they likely came from the same social community. So, for the first time, we can use genetics to study the social organization of a Neanderthal community," says Laurits Skov, who is first author on this study.

Another striking finding is the extremely low genetic diversity within this Neanderthal community, consistent with a group size of 10 to 20 individuals. This is much lower than those recorded for any ancient or present-day human community, and is more similar to the group sizes of endangered species at the verge of extinction.

However, Neanderthals didn't live in completely isolated communities. By comparing the genetic diversity on the Y-chromosome, which is inherited father-to-son, with the mitochondrial DNA diversity, which is inherited from mothers, the researchers could answer the question: Was it the men or the women who moved between communities? They found that the mitochondrial genetic diversity was much higher than the Y chromosome diversity, which suggests that these Neanderthal communities were primarily linked by female migration. Despite the proximity to Denisova Cave, these migrations do not appear to have involved Denisovans -- the researchers found no evidence of Denisovan gene flow in the Chagyrskaya Neanderthals in the last 20,000 years before these individuals lived.

Read more at Science Daily

Modern humans generate more brain neurons than Neanderthals

The question of what makes modern humans unique has long been a driving force for researchers. Comparisons with our closest relatives, the Neanderthals, therefore provide fascinating insights. The increase in brain size, and in neuron production during brain development, are considered to be major factors for the increased cognitive abilities that occurred during human evolution. However, while both Neanderthals and modern humans develop brains of similar size, very little is known about whether modern human and Neanderthal brains may have differed in terms of their neuron production during development.

Researchers from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden now show that the modern human variant of the protein TKTL1, which differs by only a single amino acid from the Neanderthal variant, increases one type of brain progenitor cells, called basal radial glia, in the modern human brain. Basal radial glial cells generate the majority of the neurons in the developing neocortex, a part of the brain that is crucial for many cognitive abilities. As TKTL1 activity is particularly high in the frontal lobe of the fetal human brain, the researchers conclude that this single human-specific amino acid substitution in TKTL1 underlies a greater neuron production in the developing frontal lobe of the neocortex in modern humans than Neanderthals.

Only a small number of proteins have differences in the sequence of their amino acids -- the building blocks of proteins -- between modern humans and our extinct relatives, the Neanderthals and Denisovans. The biological significance of these differences for the development of the modern human brain is largely unknown. In fact, both, modern humans and Neanderthals, feature a brain, and notably a neocortex, of similar size, but whether this similar neocortex size implies a similar number of neurons remains unclear. The latest study of the research group of Wieland Huttner, one of the founding directors of the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, carried out in collaboration with Svante Pääbo, director at the Max Planck Institute for Evolutionary Anthropology in Leipzig, and Pauline Wimberger of the University Hospital Dresden and their colleagues, addresses just this question. The researchers focus on one of these proteins that presents a single amino acid change in essentially all modern humans compared to Neanderthals, the protein transketolase-like 1 (TKTL1). Specifically, in modern humans TKTL1 contains an arginine at the sequence position in question, whereas in Neanderthal TKTL1 it is the related amino acid lysine. In the fetal human neocortex, TKTL1 is found in neocortical progenitor cells, the cells from which all cortical neurons derive. Notably, the level of TKTL1 is highest in the progenitor cells of the frontal lobe.

Modern human TKTL1, but not Neanderthal TKTL1, leads to more neurons in embryonic mouse neocortex

Anneline Pinson, the lead author of the study and researcher in the group of Wieland Huttner, set out to investigate the significance of this one amino acid change for neocortex development. Anneline and her colleagues introduced either the modern human or the Neanderthal variant of TKTL1 into the neocortex of mouse embryos. They observed that basal radial glial cells, the type of neocortical progenitors thought to be the driving force for a bigger brain, increased with the modern human variant of TKTL1 but not with the Neanderthal variant. As a consequence, the brains of mouse embryos with the modern human TKTL1 contained more neurons.

More neurons in the frontal lobe of modern humans

After this, the researchers explored the relevance of these effects for human brain development. To this end, they replaced the arginine in modern human TKTL1 with the lysine characteristic of Neanderthal TKTL1, using human brain organoids -- miniature organ-like structures that can be grown from human stem cells in cell culture dishes in the lab and that mimic aspects of early human brain development. "We found that with the Neanderthal-type of amino acid in TKTL1, fewer basal radial glial cells were produced than with the modern human-type and, as a consequence, also fewer neurons," says Anneline Pinson. "This shows us that even though we do not know how many neurons the Neanderthal brain had, we can assume that modern humans have more neurons in the frontal lobe of the brain, where TKTL1 activity is highest, than Neanderthals." The researchers also found that modern human TKTL1 acts through changes in metabolism, specifically a stimulation of the pentose phosphate pathway followed by increased fatty acid synthesis. In this way, modern human TKTL1 is thought to increase the synthesis of certain membrane lipids needed to generate the long process of basal radial glial cells that stimulates their proliferation and, therefore, to increase neuron production.

Read more at Science Daily

Study of ancient skulls sheds light on human interbreeding with Neanderthals

Research has established that there are traces of Neandertal DNA in the genome of modern humans. Now an exploratory study that assessed the facial structure of prehistoric skulls is offering new insights, and supports the hypothesis that much of this interbreeding took place in the Near East -- the region ranging from North Africa to Iraq.

"Ancient DNA caused a revolution in how we think about human evolution," says Steven Churchill, co-author of the study and a professor of evolutionary anthropology at Duke University. "We often think of evolution as branches on a tree, and researchers have spent a lot of time trying to trace back the path that led to us, Homo sapiens. But we're now beginning to understand that it isn't a tree -- it's more like a series of streams that converge and diverge at multiple points."

"Our work here gives us a deeper understanding of where those streams came together," says Ann Ross, corresponding author of the study and a professor of biological sciences at North Carolina State University.

"The picture is really complicated," Churchill says. "We know there was interbreeding. Modern Asian populations seem to have more Neandertal DNA than modern European populations, which is weird -- because Neandertals lived in what is now Europe. That has suggested that Neandertals interbred with what are now modern humans as our prehistoric ancestors left Africa, but before spreading to Asia. Our goal with this study was to see what additional light we could shed on this by assessing the facial structure of prehistoric humans and Neandertals."

"By evaluating facial morphology, we can trace how populations moved and interacted over time," Ross explains. "And the evidence shows us that the Near East was an important crossroads, both geographically and in the context of human evolution."

For this study, the researchers collected data on craniofacial morphology from the published literature. This ultimately resulted in a data set including 13 Neandertals, 233 prehistoric Homo sapiens, and 83 modern humans.

The researchers focused on standard craniofacial measurements, which are reproducible, and used those measurements to assess the size and shape of key facial structures. This then allowed the researchers to do an in-depth analysis to determine whether a given human population was likely to have interbred with Neandertal populations, as well as the extent of that likely interbreeding.

"Neandertals had big faces," Churchill says. "But size alone doesn't establish any genetic link between a human population and Neandertal populations. Our work here involved a more robust analysis of the facial structures."

The researchers also accounted for environmental variables that are associated with changes in human facial characteristics, to determine the likelihood that connections they established between Neandertal and human populations were the result of interbreeding rather than other factors.

"We found that the facial characteristics we focused on were not strongly influenced by climate, which made it easier to identify likely genetic influences," Ross says. "We also found that facial shape was a more useful variable for tracking the influence of Neandertal interbreeding in human populations over time. Neandertals were just bigger than humans. Over time, the size of human faces became smaller, generations after they had bred with Neandertals. But the actual shape of some facial features retained evidence of interbreeding with Neandertals."

"This was an exploratory study," Churchill says. "And, honestly, I wasn't sure this approach would actually work -- we have a relatively small sample size, and we didn't have as much data on facial structures as we would have liked. But, ultimately, the results we got are really compelling.

Read more at Science Daily

Taking your time makes a difference

Neanderthals are the closest relatives to modern humans. Comparisons with them can therefore provide fascinating insights into what makes present-day humans unique, for example regarding the development of the brain. The neocortex, the largest part of the outer layer of the brain, is unique to mammals and crucial for many cognitive capacities. It expanded dramatically during human evolution in species ancestral to both Neanderthals and modern humans, resulting that both Neanderthals and modern humans having brains of similar sizes. However, almost nothing is known about how modern human and Neanderthal brains may have differed in terms of their development and function.

Researchers from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden and the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) in Leipzig have now discovered that neural stem cells -- the cells from which neurons in the developing neocortex derive -- spend more time preparing their chromosomes for division in modern humans than in Neanderthals. This results in fewer errors when chromosomes are distributed to the daughter cells in modern humans than in Neanderthals or chimpanzees, and could have consequences for how the brain develops and functions. This study shows cellular differences in the development of the brain between modern humans and Neanderthals.

After the ancestors of modern humans split from those of Neanderthals and Denisovans, their Asian relatives, about one hundred amino acids, the building blocks of proteins in cells and tissues, changed in modern humans and spread to almost all modern humans. The biological significance of these changes is largely unknown. However, six of those amino acid changes occurred in three proteins that play key roles in the distribution of chromosomes, the carriers of genetic information, to the two daughter cells during cell division.

The effects of the modern human variants on brain development

To investigate the significance of these six changes for neocortex development, the scientists first introduced the modern human variants in mice. Mice are identical to Neanderthals at those six amino acid positions, so these changes made them a model for the developing modern human brain. Felipe Mora-Bermúdez, the lead author of the study, describes the discovery: "We found that three modern human amino acids in two of the proteins cause a longer metaphase, a phase where chromosomes are prepared for cell division, and this results in fewer errors when the chromosomes are distributed to the daughter cells of the neural stem cells, just like in modern humans." To check if the Neanderthal set of amino acids have the opposite effect, the researchers then introduced the ancestral amino acids in human brain organoids -- miniature organ-like structures that can be grown from human stem cells in cell culture dishes in the lab and that mimic aspects of early human brain development. "In this case, metaphase became shorter and we found more chromosome distribution errors." According to Mora-Bermúdez, this shows that those three modern human amino acid changes in the proteins known as KIF18a and KNL1 are responsible for the fewer chromosome distribution mistakes seen in modern humans as compared to Neanderthal models and chimpanzees. He adds that "having mistakes in the number of chromosomes is usually not a good idea for cells, as can be seen in disorders like trisomies and cancer."

Red more at Science Daily

When did the genetic variations that make us human emerge?

The study of the genomes of our closest relatives, the Neanderthals and Denisovans, has opened up new research paths that can broaden our understanding of the evolutionary history of Homo sapiens. A study led by the University of Barcelona has made an estimation of the time when some of the genetic variants that characterise our species emerged. It does so by analysing mutations that are very frequent in modern human populations, but not in these other species of archaic humans.

The results, published in the journal Scientific Reports, show two moments in which mutations accumulated: one around 40,000 years ago, associated with the growth of the Homo sapiens population and its departure from Africa, and an older one, more than 100,000 years ago, related to the time of the greatest diversity of types of Homo sapiens in Africa.

"The understanding of the deep history of our species is expanding rapidly. However, it is difficult to determine when the genetic variants that distinguish us from other human species emerged. In this study, we have placed species-specific variants on a timeline. We have discovered how these variants accumulate over time, reflecting events such as the point of divergence between Homo sapiens and other human species around 100,000 years ago," says Alejandro Andirkó, first author of this article, which was part of his doctoral thesis at the UB.

The study, led by Cedric Boeckx, ICREA research professor in the section of General Linguistics and member of the Institute of Complex Systems of the UB (UBICS), included the participation of Juan Moriano, UB researcher, Alessandro Vitriolo and Giuseppe Testa, experts from the University of Milan and the European Institute of Oncology, and Martin Kuhlwilm, researcher at the University of Vienna.

Predominance of behavioural and facial-related variations

The results of the research study also show differences between evolutionary periods. Specifically, they highlight the predominance of genetic variants related to behaviour and facial structure -- key characteristics in the differentiation of our species from other human species -- more than 300,000 years ago, a date that coincides with the available fossil and archaeological evidence. "We have discovered sets of genetic variants which affect the evolution of the face and which we have dated between 300,000 and 500,000 years ago, the period just prior to the dating of the earliest fossils of our species, such as the ones discovered at the Jebel Irhoud archaeological site in Morocco," notes Andirkó.

The researchers also analysed variants related to the brain, the organ that can best help explain key features of the rich repertoire of behaviours associated with Homo sapiens. Specifically, they dated variants which medical studies conducted in present-day humans have linked to the volume of the cerebellum, corpus callosum and other structures. "We found that brain tissues have a particular genomic expression profile at different times in our history; that is, certain genes related to neural development were more highly expressed at certain times," says the researcher.

Supporting the mosaic nature of the evolution of Homo sapiens

These results complement an idea that is dominant in evolutionary anthropology: that there is no linear history of human species, but that different branches of our evolutionary tree coexisted and often intersected. "The breadth of the range of human diversity in the past has surprised anthropologists. Even within Homo sapiens there are fossils, such as the ones I mentioned earlier from Jebel Irhoud, which, because of their features, were thought to belong to another species. That's why we say that human beings have lived a mosaic evolution," he notes.

"Our results," the researcher continues, "offer a picture of how our genetics changed, which fits this idea, as we found no evidence of evolutionary changes that depended on one or a several key mutations," he says.

Application of machine learning techniques

The methodology used in the study was based on a Genealogical Estimation of Variant Age method, developed by researchers at the University of Oxford. Once they had this estimation, they applied a machine learning tool to predict which genes have changed the most in certain time windows and which tissues these genes may have impacted. Specifically, they used ExPecto, a deep learning tool that uses a convolutional network -- a type of computational model -- to predict gene expression levels and function from a DNA sequence.

"Since there are no data on the genomic expression of variants in the past, this tool is an approach to a problem that has not been addressed until now. Although the use of machine learning prediction is increasingly common in the clinical world, as far as we know, nobody has tried to predict the consequences of genomic changes over time," notes Andirkó.

The importance of the perinatal phase in the brain development of our species

In a previous study, the same UB team, together with the researcher Raül Gómez Buisán, used genomic information from archaic humans. In that study they analysed genomic deserts, regions of the genome of our species where there are no genetic fragments of Neanderthals or Denisovans, and which, moreover, have been subjected to positive pressure in our species: that is, they have accumulated more mutations than would have been expected by neutral evolution. The researchers studied the expression of genes -- i.e., which proteins code for different functions -- found in desert regions throughout brain development, from prenatal to adult stages, covering sixteen brain structures. The results showed differences in gene expression in the cerebellum, striatum and thalamus. "These results bring into focus the relevance of brain structures beyond the neocortex, which has traditionally dominated research on the evolution of the human brain," says Juan Moriano.

Read more at Science Daily

What oxytocin can tell us about the evolution of human prosociality

Modern humans are characterized by their prosociality, a broad term that encompasses intraspecies empathy, social tolerance, cooperation and altruism. These facets of social cognition have been associated with variations in the oxytocin and vasotocin genes (OT and VT) and their receptors (OTR and VTR).To shed light on the genetic basis of this behaviour, scientists from the University of Barcelona (UB) and Rockefeller University carried out a new study comparing the available genomic sequences of these genes between modern humans, non-human primate species (e.g., chimpanzees, bonobos, and macaques) and, for the first time, archaic humans, using all the available genomes of Neanderthals and Denisovans.

In the study, published in the journal Comprehensive Psychoneuroendocrinology, the researchers identified several sites in which modern humans differed from both archaic humans and non-human primates, and others where both modern and archaic humans differed from non-human primates.

"We used an interdisciplinary approach to understand the evolution of hominid prosociality through the lens of the oxytocin and vasotocin receptors, where we combined evidence from modern and archaic genomics, population genetics, transcriptomics, and behavioural and neuroscientific studies, among other methods. These results can shed light on the genetics underlying possible sociality differences identified between modern humans and archaic humans, as well as the similarities between the modern human and bonobo social behaviour," said first author Constantina Theofanopoulou. This research is part of her doctoral thesis carried out under the co-supervision of Cedric Boeckx, ICREA researcher at the Institute of Complex Systems at the UB (UBICS) and Erich D. Jarvis, professor at Rockefeller University.

Variants unique to modern humans in more than 70% of the population

Considering the evidence on modern human prosociality and on the involvement of the oxytocin and vasotocin genes in social behaviours, the researchers hypothesized that the evolution of these genes might elucidate the genetic basis of the evolution of hominin prosociality. With this aim in mind, the study explored the differences between modern humans, archaic humans and non-human primates in polymorphic heterozygous sites in the human genome -- locations where at least two alternative sequences are found in a population. "Past studies that compared the entire modern human genome with the Neanderthal or the chimpanzee genomes have focused on changes that are fixed or nearly fixed in modern humans. This has led to them identifying sites where, for example, all Neanderthals had Adenine (one of the four nucleotides that with guanine, cytosine and thymine form the DNA) and nearly all modern humans (say, 98%) have Guanine. In this study, we searched for differences on locations where, by definition, not all modern humans share the same nucleotide, namely on polymorphic sites, where for example, 70% of the modern human population has Adenine and 30% Cytosine," adds Theofanopoulou.

The researchers identified five sites in the oxytocin and vasotocin receptors where modern humans are unique in one of their two (or more) variants compared to archaic humans and non-human primates, and which are at the same time found in more than 70% of the modern human population. Next, they conducted functional and frequency analyses to establish whether the variants are relevant. They performed a range of analyses on the five sites and found that some of the variants are highly functional, indicating that they have an effect on the molecular function of the proteins activated by these genes.

The researchers also found that these sites are encountered in genome regions that are active in the brain, particularly in the cingulate gyrus, a brain region involved in social cognition-relevant pathways. Moreover, all these sites have been associated in other studies with a plethora of social behaviours or social deficits, such as autism, attention deficit hyperactivity disorder (ADHD), aggression, and so on.

These findings may help to explain some of the social differences between modern humans and what we presume to know about the social behaviours of Neanderthals and Denisovans. "For example, they might be relevant to the smaller social groups attributed to Neanderthals and Denisovans or to the decreased modern human androgenization. They might also be relevant to a different social structure, i.e., Neanderthals have been linked to a polygynous social structure and a higher level of male-male competition than most contemporary modern human populations," says Constantina Theofanopoulou.

Variants present only in modern and archaic humans

The study also found two sites on the oxytocin receptor under a positive selection in modern and archaic humans: that is to say, modern and archaic humans showed a variant that was not present in any other non-human primate. This means that these sites are found in very high percentages in the modern human population (in this case, more than 85%). These same sites have also been associated with a great many social behaviours or deficits, and one of them was predicted to be a highly functional site in their regulation analyses. "The sites that are unique in both us and archaic humans versus non-human primates can elucidate the genetic underpinnings of the progressive social tolerance needed for the intensive cultural transmission of technological innovations (e.g., fire use) in the evolution of humankind, as well as for the reduced aggression indicated by several markers in early hominid evolution, such as the reduction of male canine size and the accelerated demographic success," adds Theofanopoulou.

Convergent sites with bonobos

Lastly, the researchers found three sites where modern humans and bonobos, a primate species that shows convergence of prosocial behaviours with humans, have the same nucleotide. "The convergent sites in modern humans and bonobos could be insightful for understanding the posited similarities in prosociality, social tolerance and cooperation between us and bonobos, and the differences of both compared to chimpanzees. For example, bonobos outperform chimpanzees on tasks relevant to social causality or theory of mind and are more attentive to the face and eyes, suggestive of higher empathic sensitivity," notes the researcher.

All the sites identified in this study have also been independently associated with disorders that include social deficits, such as autism spectrum disorders (ASD). "Understanding developmental disorders through evolutionary lenses can aid into us achieving what we call an evo-devo (evolutionary and developmental biology) understanding of these disorders. If indeed "ontogeny recapitulates phylogeny," then deciphering our evolutionary trajectory may shed light to new genetic spots for clinical research that might, in turn, lead to earlier disorder diagnosis," highlights Constantina Theofanopoulou.

Read more at Science Daily

Modern humans developed a more effective protection against oxidative stress

Very few proteins in the body have a change that makes them unique compared to the corresponding proteins in Neanderthals and apes. Researchers at the Max Planck Institute for Evolutionary Anthropology in Germany and Karolinska Institutet in Sweden have now studied one such protein, glutathione reductase, which protects against oxidative stress. They show that the risk for inflammatory bowel disease and vascular disease is increased several times in people carrying the Neanderthal variant.

What makes modern humans unique is a question that has eluded researchers for a long time. One way to approach this question is to study the proteins, or building blocks, in the body that have changes that are carried by almost all living people today and occurred after we separated from the ancestors we shared with Neanderthals about 500,000 years ago. There are around 100 proteins that have such a unique change. One of these proteins is glutathione reductase which is part of the body's defense against oxidative stress.

The study, which is published in the journal Science Advances, examines the change in glutathione reductase in detail and was led by Hugo Zeberg at Karolinska Institutet and the Max Planck Institute for Evolutionary Anthropologyand Svante Pääbo at the Max Planck Institute. They show that the Neanderthal protein created more reactive oxygen radicals which are the cause of oxidative stress. It is the third protein change unique to present-day humans that has been studied so far.

The study also shows that the Neanderthal protein has passed over to present-day humans in low frequency when our ancestors mixed with them about 60,000 years ago. Today, it occurs mainly on the Indian subcontinent at an estimated frequency of 1 to 2 per cent of the population. The researchers found that people who carry the Neanderthal protein have a higher risk of developing vascular disease and inflammatory bowel disease, both diseases that are linked to oxidative stress.

"The risk increases we see are large; several times increased risk of inflammatory bowel disease and vascular disease," says Hugo Zeberg.

The researchers can only speculate about why this particular change came to be one of the unique changes that almost all modern humans carry.

"Stopping oxidative stress is a bit like preventing something from rusting. Perhaps the fact that we are living longer has driven these changes," says Svante Pääbo.

Read more at Science Daily

How DNA is preserved in archaeological sediments for thousands of years

Sediments in which archaeological finds are embedded have long been regarded by most archaeologists as unimportant by-products of excavations. However, in recent years it has been shown that sediments can contain ancient biomolecules, including DNA. "The retrieval of ancient human and faunal DNA from sediments offers exciting new opportunities to investigate the geographical and temporal distribution of ancient humans and other organisms at sites where their skeletal remains are rare or absent," says Matthias Meyer, senior author of the study and researcher at the Max Planck Institute for Evolutionary Anthropology in Leipzig.

To investigate the origin of DNA in the sediment, Max Planck researchers teamed up with an international group of geoarchaeologists -- archaeologists who apply geological techniques to reconstruct the formation of sediment and sites -- to study DNA preservation in sediment at a microscopic scale. They used undisturbed blocks of sediment that had been previously removed from archaeological sites and soaked in synthetic plastic-like (polyester) resin. The hardened blocks were taken to the laboratory and sliced in sections for microscopic imaging and genetic analysis.

The researchers successfully extracted DNA from a collection of blocks of sediment prepared as long as 40 years ago, from sites in Africa, Asia, Europe and North America. "The fact that these blocks are an excellent source of ancient DNA -- including that originating from hominins -- despite often decades of storage in plastic, provides access to a vast untapped repository of genetic information. The study opens up a new era of ancient DNA studies that will revisit samples stored in labs, allowing for analysis of sites that have long since been back-filled, which is especially important given travel restriction and site inaccessibility in a pandemic world," says Mike Morley from Flinders University in Australia who led some of the geoarchaeological analyses.

Abundance of micro remains in the sediment matrix

The scientists used blocks of sediment from Denisova Cave, a site located in the Altai Mountains in South Central Siberia where ancient DNA from Neanderthals, Denisovans and modern humans has been retrieved, and showed that small organic particles yielded more DNA than sediment sampled randomly. "It clearly shows that the high success rate of ancient mammalian DNA retrieval from Denisova Cave sediments comes from the abundance of micro remains in the sediment matrix rather than from free extracellular DNA from feces, bodily fluids or decomposing cellular tissue potentially adsorbed onto mineral grains," says Vera Aldeias, co-author of the study and researcher at the University of Algarve in Portugal. "This study is a big step closer to understand precisely where and under what conditions ancient DNA is preserved in sediments," says Morley.

The approach described in the study allows highly localized micro-scalesampling of sediment for DNA analyses and shows that ancient DNA (aDNA) is not uniformly distributed in the sediment; and that specific sediment features are more conducive to ancient DNA preservation than others. "Linking sediment aDNA to the archaeological micro-context means that we can also address the possibility of physical movement of aDNA between sedimentary deposits," says Susan Mentzer a researcher at the Senckenberg Centre for Human Evolution and Palaeoenvironment (Germany).

Read more at Science Daily