Oldest modern human genomes sequenced
Genomes of seven early Europeans show they belonged to a small, isolated group that had recently mixed with Neandertals but left no present-day descendants
Max Planck Institute for Evolutionary Anthropology
image:
Illustration of Zlatý kůň, who belonged to the same population as the Ranis individuals and was closely related to two of them.
view moreCredit: © Tom Björklund for Max Planck Institute for Evolutionary Anthropology
After modern humans left Africa, they met and interbred with Neandertals, resulting in around two to three percent Neandertal DNA that can be found in the genomes of all people outside Africa today. However, little is known about the genetics of these first pioneers in Europe and the timing of the Neandertal admixture with non-Africans.
A key site in Europe is Zlatý kůň in Czechia, where a complete skull from a single individual who lived around 45,000 years ago was discovered and previously genetically analyzed. However, due to the lack of archaeological context, it was not possible to link this individual to any archaeologically defined group. A nearby site, the Ilsenhöhle in Ranis in Germany, about 230 km from Zlatý kůň, is known for a specific type of archaeology, the Lincombian-Ranisian-Jerzmanowician (LRJ), which dates to around 45,000 years ago. It has long been debated whether the LRJ culture was produced by Neandertals or early modern humans. Although mostly small fragments of bones are preserved in Ranis, a previous study was able to analyze mitochondrial DNA from thirteen of these remains and found that they belonged to modern humans and not Neandertals. However, since the mitochondrial sequence only constitutes a miniscule part of the genetic information, the relationships to other modern humans remained a mystery.
Linking Zlatý kůň and Ranis
A new study published today in Nature analyzed the nuclear genomes of the thirteen specimens from Ranis and found that they represented at least six individuals. The size of the bones indicated that two of these individuals were infants and, genetically, three were males and three were females. Interestingly, among these individuals were a mother and daughter, as well as other, more distant, biological relatives. The team also sequenced more DNA from the female skull found at Zlatý kůň, producing a high-quality genome for this individual. ”To our surprise, we discovered a fifth- or sixth-degree genetic relationship between Zlatý kůň and two individuals from Ranis.” says Arev Sümer, lead author of the study, ”This means that Zlatý kůň was genetically part of the extended family of Ranis and likely also made LRJ-type tools”.
Among the six individuals from Ranis, one bone was particularly well preserved, in fact it is the best preserved modern human bone from the Pleistocene for DNA retrieval. This allowed the team to obtain a high-quality genome from this male individual, referred to as Ranis13. Together, the Ranis13 and Zlatý kůň genomes represent the oldest high-quality modern human genomes sequenced to date. When analyzing genetic variants related to phenotypic traits, they found that Ranis and Zlatý kůň individuals carried variants associated with dark skin and hair color as well as brown eyes, reflecting the recent African origin of this early European population.
By analyzing the segments inherited from the same ancestor in the Ranis and Zlatý kůň genomes, the researchers estimate that their population consisted of at most a few hundred individuals who may have been spread out over a larger territory. The authors found no evidence that this small early modern human population contributed to later Europeans or any other world-wide population.
A narrower timeframe for the shared Neandertal admixture
Members of the Zlatý kůň/Ranis population coexisted with Neandertals in Europe, raising the possibility that they may have had Neandertals among their recent ancestors after they migrated to Europe. Previous studies on modern humans from over 40,000 years ago, had found evidence of such recent admixture events between modern humans and Neandertals. However, no such evidence for recent Neandertal admixture was detected in the genomes of the Zlatý kůň/Ranis individuals. “The fact that modern human groups, which may have arrived in Europe later, carry such Neandertal ancestry while Ranis and Zlatý kůň do not could mean that the older Zlatý kůň/Ranis lineage may have entered Europe by a different route or did not overlap as extensively with the regions where Neandertals lived” speculates Kay Prüfer, who co-supervised the study.
The Zlatý kůň/Ranis population represents the earliest known divergence from the group of modern humans that migrated out of Africa and dispersed later across Eurasia. Despite this early separation, the Neandertal ancestry in Zlatý kůň and Ranis originated from the same ancient admixture event that can be detected in all people outside Africa today. By analyzing the length of the segments contributed from Neandertals in the high-coverage Ranis13 genome and using direct radiocarbon dates on this individual, the researchers dated this shared Neandertal admixture to between 45,000 and 49,000 years ago. Since all present-day non-African populations share this Neandertal ancestry with Zlatý kůň and Ranis, this means that around 45,000 to 49,000 years ago, a coherent ancestral non-African population must still have existed.
“These results provide us with a deeper understanding of the earliest pioneers that settled in Europe,” says Johannes Krause, senior author of the study. “They also indicate that any modern human remains found outside Africa that are older than 50,000 years could not have been part of the common non-African population that interbred with Neanderthals and is now found across much of the world.”
Illustration of the Zlatý kůň/Ranis group. Around 45,000 years ago, individuals from Ranis in Germany and Zlatý kůň in Czechia likely traveled together across the open steppe landscapes of Europe.
Credit
© Tom Björklund for Max Planck Institute for Evolutionary Anthropology
Journal
Nature
Article Title
Earliest modern human genomes constrain timing of Neanderthal admixture
Article Publication Date
12-Dec-2024
New timeline for Neandertal gene flow event
Scientists unravel timing and impact of Neandertal gene flow into early modern humans
image:
The researchers identified regions with Neandertal ancestry in over 300 individuals. They assessed sharing of segments, inferred gene flow, and looked at variation to identify candidates for positive and negative selection.
view moreCredit: © Leonardo Iasi et al., Science (2024)
The study of ancient DNA has greatly advanced our knowledge of human evolution, including the discovery of gene flow from Neandertals into the common ancestors of modern humans. Neandertals and modern humans diverged about 500,000 years ago, with Neandertals living in Eurasia for the past 300,000 years. Then, sometime around 40,000 to 60,000 years ago, modern human groups left Africa and spread across Eurasia, encountering Neandertals along the way. As a result, most non-Africans harbor one to two percent Neandertal ancestry today. However, the precise timing and functional legacy of Neandertals remains elusive.
In a new study, researchers from the Max Planck Institute for Evolutionary Anthropology, Leipzig, and the University of California, Berkeley, examined the genomes of 300 present-day and ancient modern humans, including 59 individuals who lived between 2,000 and 45,000 years ago. "We set out to determine the timing and duration of Neandertal gene flow and the resulting impact on modern humans. To do this, we created a catalog of Neandertal ancestry segments. By comparing the segments among individuals from different time periods and geographic locations, we were able to show that the vast majority of Neandertal ancestry can be traced to a single, shared, extended period of gene flow into the common ancestors of all non-African individuals today," says Priya Moorjani from the University of California, Berkeley.
Neandertal ancestry revisited
By observing the length of the Neandertal DNA segments, which is related to the number of generations since the gene flow, the researchers inferred that the gene flow began about 50,000 years ago and continued for about 7,000 years. "This timeline closely matches the archaeological evidence for the overlap of Neandertals and modern humans in Europe. Some early modern humans - Oase, Ust'-Ishim, Zlatý kůň, and Bacho Kiro - possess substantial unique Neandertal ancestry that is not shared with modern humans after 40,000 years," says first author Leonardo Iasi from the Max Planck Institute for Evolutionary Anthropology.
These dates have several implications for human dispersal after the Out-of-Africa event, as they provide a lower bound on the timing of migration and the settlement of regions outside of Africa. For example, this suggests that the major migration out of Africa occurred no later than 43,500 years ago. Moreover, the population receiving Neandertal ancestry may have been highly structured during the gene flow event. "Diversification of humans outside of Africa may have begun during or soon after the Neandertal gene flow, which could partially explain the different levels of Neandertal ancestry among non-African populations and also reconcile our dates with archaeological evidence for the presence of modern humans in Southeast Asia and Oceania by about 47,000 years,“ says Benjamin Peter from the Max Planck Institute for Evolutionary Anthropology and the University of Rochester. "Studying more ancient genomes from Eurasia and Oceania could further our understanding of when humans spread to these regions.“
Functional impact of Neandertal ancestry
To understand the functional legacy of Neandertal ancestry, the researchers examined changes in Neandertal ancestry across the genome and over time. They identified some Neandertal regions that are present at high frequency, possibly because they were beneficial as early modern humans began to explore new environments outside of Africa. "These include genes related to immune function, skin pigmentation and metabolism," says Manjusha Chintalapati from the University of California, Berkeley. "On the other hand, there are also large regions of the genome that are completely devoid of Neandertal ancestry. These regions formed rapidly after the gene flow and were also absent from the earliest modern human genomes, 30,000 to 45,000-year-old individuals. Many Neandertal sequences may have been deleterious to humans and were therefore actively and rapidly selected against by evolution.“
This study sheds light on the complex history of gene flow from Neandertals into modern humans. It also highlights the power of genomic data to elucidate the legacy of human migrations and gene flow.
Journal
Science
Article Title
Neanderthal ancestry through time: Insights from genomes of ancient and present-day humans
Article Publication Date
13-Dec-2024
A new timeline for Neanderthal interbreeding with modern humans
Surviving Neanderthal genes in modern genome tell a story of thousands of years of interactions
image:
Illustration of an encounter between a group of Neanderthals (black) and a group of modern humans (red, top row) with offspring showing recent Neanderthal ancestry (red, bottom row), imagined as a cave art painting. DNA from bones and teeth of these early human ancestors is helping scientists understand the interactions between early Homo sapiens and the Neanderthals they encountered after migrating out of Africa.
view moreCredit: Leonardo Iasi, MPI-EVA. Figure created with Dall-E and BioRender.com
A new analysis of DNA from ancient modern humans (Homo sapiens) in Europe and Asia has determined, more precisely than ever, the time period during which Neanderthals interbred with modern humans, starting about 50,500 years ago and lasting about 7,000 years — until Neanderthals began to disappear.
That interbreeding left Eurasians with many genes inherited from our Neanderthal ancestors, which in total make up between 1% and 2% of our genomes today.
The genome-based estimate is consistent with archeological evidence that modern humans and Neanderthals lived side-by-side in Eurasia for between 6,000 and 7,000 years. The analysis, which involved present-day human genomes as well as 58 ancient genomes sequenced from DNA found in modern human bones from around Eurasia, found an average date for Neanderthal-Homo sapiens interbreeding of about 47,000 years ago. Previous estimates for the time of interbreeding ranged from 54,000 to 41,000 years ago.
The new dates also imply that the initial migration of modern humans from Africa into Eurasia was basically over by 43,500 years ago.
"The timing is really important because it has direct implications on our understanding of the timing of the out-of-Africa migration as most non-Africans today inherit 1-2% ancestry from Neanderthals," said Priya Moorjani, an assistant professor of molecular and cell biology at the University of California, Berkeley, and one of two senior authors of the study. "It also has implications for understanding the settlement of the regions outside Africa, which is typically done by looking at archeological materials or fossils in different regions of the world."
The genome analysis, also led by Benjamin Peter of the University of Rochester in New York and the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) in Leipzig, Germany, will be published in the Dec. 13 print issue of the journal Science. The two lead authors are Leonardo Iasi, a graduate student at MPI-EVA, and Manjusha Chintalapati, a former UC Berkeley postdoctoral fellow now at the company Ancestry DNA.
The longer duration of gene flow may help explain, for example, why East Asians have about 20% more Neanderthal genes than Europeans and West Asians. If modern humans moved eastward about 47,000 years ago, as archeological sites suggest, they would already have had intermixed Neanderthal genes.
"We show that the period of mixing was quite complex and may have taken a long time. Different groups could have separated during the 6,000- to 7,000-year period and some groups may have continued mixing for a longer period of time," Peter said. "But a single shared period of gene flow fits the data best."
"One of the main findings is the precise estimate of the timing of Neanderthal admixture, which was previously estimated using single ancient samples or in present-day individuals. Nobody had tried to model all of the ancient samples together," Chintalapati said. “ This allowed us to build a more complete picture of the past”
Neanderthal deserts in the genome
In 2016, Moorjani pioneered a method for inferring the timing of Neanderthal gene flow using often incomplete genomes of ancient individuals. At that time, only five archaic Homo sapiens genomes were available. For the new study, Iasi, Chintalapati and their colleagues employed this technique with 58 previously sequenced genomes of ancient Homo sapiens who lived in Europe, Western and Central Asia over the past 45,000 years and the genomes of 275 worldwide contemporary humans to provide a more precise date — 47,000 years ago. Rather than assuming the gene flow occurred in a single generation, they tried more complex models developed by Iasi and Peter to establish that the interbreeding extended over about 7,000 years, rather than being intermittent.
The timing of the interbreeding between Neanderthals and modern humans was corroborated by another, independent study conducted by MPI-EVA researchers and scheduled to be published Dec. 12 in the journal Nature. That study, an analysis of two newly sequenced genomes of Homo sapiens that lived about 45,000 years ago, also found a date of 47,000 years ago.
"Although the ancient genomes were published in previous studies, they had not been analyzed to look at Neanderthal ancestry in this detailed way. We created a catalog of Neanderthal ancestry segments in modern humans. By jointly analyzing all these samples together, we inferred the period of gene flow was around 7,000 years," Chintalapati said. "The Max Planck group actually sequenced new ancient DNA samples that allowed them to date the Neanderthal gene flow directly. And they came up with a similar timing as us."
The UC Berkeley/MPI-EVA team also analyzed regions of the modern human genome that contain genes inherited from Neanderthals and some areas that are totally devoid of Neanderthal genes. They found that areas lacking any Neanderthal genes, so-called archaic or Neanderthal deserts, developed quickly after the two groups interbred, suggesting that some Neanderthal gene variants in those areas of the genome must have been lethal to modern humans.
Early modern human samples that are older than 40,000 years — samples from Oase cave in Romania, Ust'-Ishim in Russia, Zlatý kůň in the Czech Republic, Tianyuan in China and Bacho Kiro in Bulgaria — already contained these deserts in their genomes.
"We find that very early modern humans from 40,000 years ago don't have any ancestry in the deserts, so these deserts may have formed very rapidly after the gene flow," said Iasi. "We also looked at the changes in Neanderthal ancestry frequency over time and across the genome and found regions that are present at high frequency, possibly because they carry beneficial variants that were introgressed from Neanderthals."
Most of the high-frequency Neanderthal genes are related to immune function, skin pigmentation and metabolism, as reported in some previous studies. One immune gene variant inherited from Neanderthals confers protective effects to coronavirus that causes COVID-19, for example. Some of the Neanderthal genes involved in the immune system and skin pigmentation actually increased in frequency in Homo sapiens over time, implying that they may have been advantageous to human survival.
"Neanderthals were living outside Africa in harsh, Ice Age climates and were adapted to the climate and to the pathogens in these environments. When modern humans left Africa and interbred with Neanderthals, some individuals inherited Neanderthal genes that presumably allowed them to adapt and thrive better in the environment," Iasi said.
"The fact that we find some of these regions already in 30,000-year-old samples shows that some of these regions were actually adapted immediately after the introgression," Chintalapati added.
Other genes, such as the gene conferring resistance to coronaviruses, may not have been immediately useful but became useful later on.
"The environment changes and then some genes become beneficial," Peter said.
Moorjani is currently looking at Neanderthal sequences in people of East Asian descent, who not only have a greater percentage of Neanderthal genes, but also somegenes — up to 0.1% of their genome — from another early hominin group, the Denisovans.
"It's really cool that we can actually peer into the past and see how variants inherited from our evolutionary cousins, Neanderthals and Denisovans, changed over time," Moorjani said. "This allows us to understand the dynamics of the mixture of Neanderthals and modern humans."
Other co-authors of the Science paper were postdoctoral fellow Laurits Skov of UC Berkeley and Alba Bossoms Mesa and Mateja Hajdinjak of MPI-EVA. Moorjani's research was supported by the Burroughs Wellcome Fund and the National Institutes of Health (R35GM142978).
Journal
Science
Subject of Research
People
Article Title
Neandertal ancestry through time: Insights from genomes of ancient and present-day humans
Article Publication Date
13-Dec-2024
Genomic analysis refines timing of Neandertal admixture – and its impact on modern humans
Summary author: Walter Beckwith
A genomic study encompassing more than 300 genomes spanning the last 50,000 years has revealed how a single wave of Neandertal gene flow into early modern humans left an indelible mark on human evolution. Among other findings, the study reports that modern humans acquired several Neanderthal genes that ended up being advantageous to our lineage, including those involved in skin pigmentation, immune response, and metabolism. To date, sequencing of Neanderthal and Denisovan genomes has revealed substantial gene flow between these archaic hominins and modern human ancestors, even as scientists have also reported that Neanderthal ancestry is unevenly distributed across the genome. Moreover, certain regions of the genome – known as archaic deserts – completely lack Neandertal ancestry, while others exhibit high frequencies of Neanderthal variants, potentially due to beneficial adaptive mutations. However, much about the nature of this ancient admixture, including the role evolutionary forces like genetic drift or natural selection played in shaping these patterns, remains unclear. Using genomic data from 334 modern humans, including 59 ancient individuals ranging from 45,000 to 2,200 years old, and 275 present-day individuals from diverse global populations, Leonardo Iasi et al. performed a comprehensive evaluation of Neanderthal ancestry variation in modern humans over the last ~50,000 years. Iasi et al. discovered that the vast majority of Neanderthal gene flow is attributable to a single, shared extended period of gene flow that likely occurred 50,500 to 43,500 years ago, which is consistent with archeological evidence for the overlap of modern humans and Neandertals in Europe. Additionally, the findings demonstrate that Neanderthal ancestry underwent rapid natural selection – both positive and negative – within 100 generations after gene flow, especially on the X chromosome.
Nature is publishing a related paper, “Earliest modern human genomes constrain timing of Neanderthal admixture,” embargoed for the same time (Thursday, 12 December at 2pm US ET). To obtain a copy of this paper, please email press@nature.com or visit the Springer Nature press site. An online press briefing for the two papers will take place UNDER STRICT EMBARGO on Wednesday at 3pm London time (GMT) / 10 am US Eastern Time. To attend this briefing please pre-register here.
Journal
Science
Article Title
Neandertal ancestry through time: Insights from genomes of ancient and present-day humans
Article Publication Date
13-Dec-2024
No comments:
Post a Comment