IMAGE: HUGO ZEBERG, ASSISTANT PROFESSOR AT THE DEPARTMENT OF PHYSIOLOGY AND PHARMACOLOGY, KAROLINSKA INSTITUTETview more
CREDIT: PHOTO: ALEXANDER DONKA
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.
The study was financed by The Swedish Research Council, The Swedish Brain Foundation, The Erik Philip-Sörensen Foundation, Petrus och Augusta Hedlunds Stiftelse, and Emil och Wera Cornells Stiftelse.
Publication: “Major genetic risk factors for Dupuytren's disease are inherited from Neanderthals”, Richard Ågren, Snehal Patil, Xiang Zhou, FinnGen, Kristoffer Sahlholm, Svante Pääbo and Hugo Zeberg, Molecular Biology and Evolution, online June 14, 2023, doi: 10.1093/molbev/msad130
Cultural exchanges and interbreeding between African hunter-gatherers, Neolithic European farmers, and East-Saharan herders shaped changes in lifestyles, cultural expression and genetic makeup in the Maghreb between 5500 and 4500 BC, according to a study published today in Nature.
For decades Archaeology has been trying to explain how and why humans went from being exclusively hunter-gatherers to producing food, adopting agriculture and livestock. How did the "Neolithic Revolution" happen? Where did it all begin, and how did it spread?
To answer some of these questions and, as always in Science, to pose new ones, an international team - on which the Universities of Cordoba, Huelva and Burgos participated - published today, in the journal Nature, the results of a new work that dispels some myths about the beginning of the Neolithic and, therefore, of agriculture, in North Africa about 7,500 years ago.
Until recently, archaeologists debated the origins of agriculture and livestock in North Africa; that is, whether this had arisen independently, and the humans who inhabited that territory managed to domesticate local species and develop techniques similar to those of the inhabitants of the valleys of the Tigris and the Euphrates; or whether the process had been strictly the result of a cultural transmission from other regions, such as the Near East or the Mediterranean. A new work spearheaded by the University of Uppsala and Burgos, with an important role played by the Moroccan Institute of Archaeology and Heritage Sciences (INSAP), shows that neither vision is true. Rather, the advent of the Neolithic in North Africa was the result of a complex and multifaceted process like few others, in light of the archaeological data observed thus far in the Old World all together.
The originality of the study lies in its combined genomic reading of Neolithic human remains from three key sites: the Kaf Taht el-Ghar cave, in Tetouan; Ifri n'Amr Ou Moussa, in Khémisset province; and Skhirat-Rouazi, south of Rabat. In the first the remains of a small group of individuals descended from European farmers who settled in the area around 7400 years ago were identified and studied. In the second, the existence of a necropolis in a cave has been confirmed where a couple of centuries later individuals of purely local ancestry were buried; that is, farmers with ceramics who had descended from native hunter-gatherers who adopted these new techniques from the aforementioned immigrant groups. Finally, in the third, a prehistoric necropolis dating from a thousand years later, genomes associated with the expansion of pastoral peoples from the Fertile Crescent were identified, which Archaeology had been detecting throughout present-day North Africa.
The dating of all these remains and their genomic study has allowed this Iberian-Swedish-Moroccan team (the main author is Luciana Simões, a Portuguese researcher at the University of Uppsala), to verify that the biological and cultural diversity of the humans who inhabited the territory more than 7,000 years ago could be behind the success of Neolithization in North Africa. In this regard, the work published InNature - and on which Rafael M. Martínez, of the University of Cordoba: Juan Carlos Vera, of the University of Huelva; and Cristina Valdiosera, of the University of Burgos, co-director of the project, appear as co-authors - expressly points out that long before the Romanization of the western end of the Mediterranean and, of course, long before the Islamization of the territory, human groups on both sides of the Strait of Gibraltar already shared knowledge, cultural aspects and, of course, genes.
According to Rafael M. Martínez, at the University of Córdoba, this work represents "a turning point in our understanding of many aspects related to the Neolithic diffusion processes in the region, settling the question regarding its origin in Andalusia and the Maghreb. The unidirectionality of the process now seems quite clear, probably from Iberia, situating the printed decoration of these first Moroccan ceramics in the larger set of the first adorned ceramics from the Western Mediterranean, including the Italian Peninsula, Southern France and the Iberian Mediterranean. Regarding the "pastoral" component of the necropolis of Skhirat, Martínez states that "precisely the ceramics present as trousseaus in these tombs, are completely different from the oldest printed ones, having precedents in styles previously known throughout the Sahara and decorated with rope patterns. A work of ours from 2018 already pointed out the relationship between this type of ceramics and pastoralist peoples; or, in any case, with very different origins."
Juan Carlos Vera, meanwhile, underscored that Genomics has come to ratify what archaeology has already been asserting for the last ten years: "The genetic sampling campaign was carried out in 2016, but the clear, complete image of the cultural and economic-social changes parallel to the mestizaje and population movements now demonstrated would not have been possible without the archaeological work we did in Morocco between 2011 and 2013 as part of the ERC AGRIWESTMED project, coordinated by the archaeobotanical expert Leonor Peña-Chocarro, at the CSIC (Madrid), thanks to an agreement with the Moroccan INSAP, coordinated by our colleague Youssef Bokbot. Thanks to these works, it was possible to detect ancient cereal and legume seeds grown in several of these Neolithic contexts, which already pointed to a diffusion process, although in this case we could not ascertain the 'human' scope of the process, or the immigrants' 'physical' arrival to the territory, with the projection of their genes, which this work demonstrates," says the professor at the University of Huelva.
Cristina Valdiosera, a Ramón y Cajal researcher at the University of Burgos and co-director of the project, along with Mattias Jakobsson, concluded that this is a work with enormous implications in the genomic history of North Africa. The settlers of the Maghreb, the historical Berbers (imazighen), have an ancestry made up of three main components: the first of them is that of African hunter-gatherers, present since the Upper Paleolithic in the cave of Taforalt; that of the European Neolithic farmers, who ultimately descend from the first peasants of Anatolia, spread over the Mediterranean and who probably arrived in Morocco from the Iberian Peninsula around 5500 BC; and, finally, that of the pastoralist peoples who penetrated the African continent, towards the west and south, crossing the Sinai from the fertile crescent, and who arrived in the Moroccan Atlantic approximately a thousand years later. "The fact that Berber and Semitic languages belong to the Afro-Asian linguistic trunk may be a consequence of the genomic history we are observing."
People were breeding scarlet macaws (Ara macao) in what is today New Mexico in the 1100s, according to examination of eggshell found at the Old Town archeological site. Cyler Conrad and colleagues examined six eggshell fragments associated with the articulated remains of a macaw. The eggshells are indirectly dated to the early 1100s by previous bone radiocarbon dating of the macaw. Using a non-destructive scanning electron microscope, the authors looked for evidence of fetal development inside the eggs, which can be inferred from reabsorption of a layer of eggshell known as the mammillary cone. Five specimens showed clear evidence of reabsorption, and the samples included at least two separate eggs, based on the developmental ages identified.
The presence of fertilized scarlet macaw eggs at this site strongly suggests macaw breeding was occurring at Old Town in the 1100s. This is the first evidence of macaw breeding north of Paquimé, in Northwestern Mexico, where macaw breeding was known to occur after 1275. According to the authors, the findings may help shed light on the practice of breeding and keeping macaws in the Americas. The birds are native to the rainforests of Mexico and Central America but were transported and kept by people as far north as the desert Southwest in what is now the United States as early as the 600s. Contemporary experts are not sure precisely why scarlet macaws were bred and translocated.
IMAGE: LOOKING BACK AT THE ENTRANCE OF TAM PÀ LING CAVE FROM THE CAVE FLOOR. THE EXCAVATION PIT IS THE THE LEFT OF THIS LOCATION.view more
CREDIT: COPYRIGHT KIRA WESTAWAY (MACQUARIE UNIVERSITY)
Tam Pà Ling, a cave in northern Laos, reveals new secrets about our earliest human journeys from Africa through to Australia.
Between 86,000 and 68,000 years ago, modern humans passed by a cave in mainland Southeast Asia on their way through Asia to become Australia’s First People.
Evidence for a human presence in this region lasting at least 56,000 years was found in approximately seven metres of cave sediment.
This evidence demonstrates our abilities to move through forested areas and along inland river systems, and could represent a previously-used migration path among our ancestors.
What connects a fossil found in a cave in northern Laos with stone tools made in north Australia? The answer is, we do. When our early Homo sapiens ancestors first arrived in Southeast Asia on their way from Africa to Australia, they left evidence of their presence in the form of human fossils that accumulated over thousands of years deep in a cave.
The latest evidence from Tam Pà Ling cave in northern Laos, uncovered by a team of Laotian, French, American and Australian researchers and published in Nature Communications, demonstrates beyond doubt that modern humans spread from Africa through Arabia and to Asia much earlier than previously thought.
It also confirms that our ancestors didn’t just follow coastlines and islands. They travelled through forested regions, most likely along river valleys, too. Some then moved on through Southeast Asia to become Australia’s First People.
“Tam Pà Ling plays a key role in the story of modern human migration through Asia but its significance and value is only just being recognised,” says University of Copenhagen palaeoanthropologist Assistant Professor Fabrice Demeter, one of the paper’s lead authors.
Three Australian Universities contributed to the project. Macquarie University and Southern Cross University dated samples using multiple techniques. Flinders University showed that the sediment in the cave had been laid down in distinct layers over tens of thousands of years.
Since the first excavation and the discovery of a skull and mandible in 2009, the cave has been controversial. Evidence of our earliest journeys from Africa into Southeast Asia is usually dominated by island locations such as Sumatra, Philippines and Borneo.
This was before Tam Pà Ling, an upland cave site more than 300 kilometres from the sea in northern Laos, started divulging its secrets. The skull and jawbone were identified as belonging to Homo sapiens who had migrated through the region. But when?
As is usual in questions of human dispersal, the debate comes down to timing. But this evidence was hard to date.
The human fossils cannot be directly dated as the site is a World Heritage area and the fossils are protected by Laotian law. There are very few animal bones or suitable cave decorations to date, and it is too old for radiocarbon dating. This placed a heavy burden on the luminescence dating of sediments to form the backbone of the timeline.
Luminescence dating relies on a light-sensitive signal that is reset to zero when exposed to light but builds up over time when shielded from light during burial. It was originally used to constrain the burial sediments that encased the fossils.
“Without luminescence dating this vital evidence would still have no timeline and the site would be overlooked in the accepted path of dispersal through the region,” says Macquarie University geochronologist Associate Professor Kira Westaway. “Luckily the technique is versatile and can be adapted for different challenges.”
These techniques returned a minimum age of 46,000 years – a chronology in line with the expected timing of Homo sapiens’ arrival in Southeast Asia. But the discovery didn’t end here.
From 2010 to 2023, annual excavations (delayed by three years of lockdowns) revealed increasingly more evidence that Homo sapiens had passed through en route to Australia. Seven pieces of human skeleton were found at intervals through 4.5 metres of sediment, pushing the potential timeline far back into the realms of the earliest Homo sapiens migrations to this region.
In this study, the team overcame these issues by creatively applying strategic dating techniques where possible, such as the uranium-series dating of a stalactite tip that had been buried in sediment, and the use of uranium-series dating coupled with electron-spin-resonance dating techniques to two rare but complete bovid teeth, unearthed at 6.5 metres.
“Having direct dating of the fossil remains confirmed the age sequence obtained by luminescence, allowing us to propose a comprehensive and secure chronology for a Homo sapiens presence at Tam Pà Ling,” says Southern Cross University geochronologist Associate Professor Renaud Joannes-Boyau.
The team supported the dating evidence with a detailed analysis of the sediments to assess the origin of the fossils using micromorphology, a technique that examines sediments under a microscope to establish the integrity of the layers. This key component of the new chronology helped establish that there was a consistent accumulation of sedimentary layers over a long period.
“Far from reflecting a rapid dump of sediments, the site represents a consistent and seasonally deposited stack of sediments,” explains Flinders University geoarchaeologist Associate Professor Mike Morley, who worked with PhD students Vito Hernandez and Meghan McAllister-Hayward.
The new chronology revealed there had a been a human presence in this area for more than 56,000 years. Furthermore, the age of the lowest fossil at seven metres – a fragment of a leg bone – provides a timeline for modern human arrival in this region of between 86,000 to 68,000 years ago. This pushes back the arrival time in mainland Southeast Asia by approximately 40,000 years. Although, according to the genetics, these early migrations did not contribute significantly to our modern-day populations.
“This really is the decisive paper for the Tam Pà Ling evidence,” says Associate Professor Westaway. “Finally we have enough dating evidence to confidently say when Homo sapiens first arrived in this area, how long they were there and what route they may have taken.”
Tam Pà Ling cave is very close to the recently discovered Cobra Cave, which was frequented by Denisovans approximately 70,000 years earlier. Despite the previous lack of evidence for early arrival in mainland Southeast Asia, this area might be a previously used dispersal route among our ancestors, long before Homo sapiens.
“We have much to learn from the caves and forests of Southeast Asia,” adds Associate Professor Westaway.
IMAGE: TISSUE FROM ONE OF THE MEDICI EMBALMING VESSELS WAS SUBJECTED TO MICROSCOPIC AND MOLECULAR ANALYSIS.view more
CREDIT: EURAC RESEARCH
The powerful dynasty buried its dead according to a special ritual: during embalming, the entrails were removed and placed in large terracotta vessels called orci which were buried together with the coffins in the Basilica di San Lorenzo in Florence. In 2010, researchers were allowed to sample nine of these orci which were decorated with the family’s coat-of-arms. Of the nine, two bore the names of specific family members.
Using long tweezers, the team retrieved something that at first glance seemed to Anthropologist Albert Zink who was leading the investigation, to be “rather insignificant,”. He went on to explain, “However, these fragments, which to the untrained eye, could have been pieces of cloth, were in fact mummified tissues of unknown origin. So, our first interest was to find out what we were actually looking at. Then, to find out if the structure of the organ was intact enough to see if we could identify the organ it came from.” The researchers took a total of 24 samples, which they then subjected to microscopic and molecular analyses.
The molecular investigations did not lead much further. The material was too degraded, the Arno had flooded Florence several times since the Medici period and acute temperature fluctuations had done the rest, “proteins or DNA were almost no longer present,” explains first author of the study, Microbiologist Frank Maixner. “But it wasn’t all bad news, the microscopic structure was in fact, very exciting.” Thin tissue sections revealed a potential blood vessel that still contained collections of red blood cells. When a special method called Giemsa staining was used, evidence of a parasite inside these blood cells was revealed.
What Maixner described “a surprising finding” was not conclusive. The parasites could have been plasmodia – a parasite responsible for malaria or even another parasite called babesia.
The team went on to employ an even more precise technique, atomic force microscopy whereby the tissue surface was scanned with a nanoscopic needle which rendered even the tiniest differences in height and three-dimensional structure visible. This analysis revealed the typical ring-shaped structures that characterize one of the developmental stages of the plasmodia parasites. However, the same shapes can also be formed by babesia. Finally, it was the immunohistochemical method, which enables the detection of antigens in tissue sections, that provided certainty. And so, the parasite was determined unambiguously: Plasmodium falciparum, the causative agent of the deadliest form of malaria, malaria tropica, which occurs mainly in the equatorial region.
Parasites were detected in many of the blood cells examined. In addition, typical membrane structures formed by the Plasmodium falciparum pathogen itself during the course of infection could be detected within the individual blood cells. “These so-called Maurer's clefts are cell organelles that are important for interaction between host and parasite. Among other things, they are involved in the transport of parasite proteins and as such significantly influence the course of the disease," explains co-author and Malaria Researcher Nicole Kilian from the University of Heidelberg/University Hospital Heidelberg.
In a further analysis, the scientists examined the sugar structures on the surface of the blood cells, which decisively influence blood group. The result: the infected individual belonged to blood group B and, people from this blood group are less resistant to malaria. However, it is no longer possible to find out which family member the results pertain as the orci from which the sample was taken does not bear a name.
Although the prehistoric site of Eynan-Mallaha in northern Israel has been thoroughly examined since 1955, it still holds some surprises for scientists. Seven prehistoric wind instruments known as flutes, recently identified by a Franco-Israeli team1, are the subject of an article published on 9 June in Nature Scientific Reports. The discovery of these 12,000 -year-old aerophones is extremely rare – in fact, they are the first to be discovered in the Near East. The “flutes”, made from the bones of a small waterfowl, produce a sound similar to certain birds of prey (Eurasian sparrowhawk and common kestrel) when air is blown into them. The choice of bones used to make these instruments was no accident – larger birds, with bigger bones that produce deeper sounds, have also been found at the site. The Natufians, the Near Eastern civilisation that occupied this village between 13,000 and 9,700 BC, deliberately selected smaller bones in order to obtain the high-pitched sound needed to imitate these particular raptors. The instruments may have been used for hunting, music or to communicate with the birds themselves. Indeed, it is clear that the Natufians attributed birds with a special symbolic value, as attested by the many ornaments made of talons found at Eynan-Mallaha. The village, located on the shores of Lake Hula, was home to this civilisation throughout its 3,000 years of existence. It is therefore of vital importance in revealing the practices and habits of a culture at the crossroads between mobile and sedentary lifestyles, and the transition from a predatory economy to agriculture.
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.”
The other co-lead author on the study is Christopher Robles, postdoctoral researcher at UCLA. Additional authors are UCLA doctoral student Ali Pazokitoroudi; Andrea Ganna of Massachusetts General Hospital and the Broad Institute of MIT and Harvard; Alexander Gusev and Arun Durvasula of Harvard Medical School; Steven Gazal of USC; Po-Ru Loh of the Broad Institute of MIT and Harvard; and David Reich of Harvard University.
The research was supported by grants from the National Institutes of Health and the National Science Foundation, with additional funding from an Alfred P Sloan Research Fellowship and a gift from the Okawa Foundation. Other authors received funding support from the Paul G. Allen Frontiers Group, the John Templeton Foundation, the Howard Hughes Medical Institute, the Burroughs Wellcome Fund and the Next Generation Fund at the Broad Institute of MIT and Harvard.
