Summary: New research refines the timeline of interbreeding between modern humans and Neanderthals, showing it began about 50,500 years ago and lasted roughly 7,000 years. This gene flow left non-African populations with 1-2% Neanderthal ancestry, contributing beneficial traits like immune resilience and skin pigmentation.

The study also identified Neanderthal deserts—regions in human genomes devoid of Neanderthal genes—likely caused by lethal gene variants. These findings deepen our understanding of human adaptation, migration, and the genetic legacy from Neanderthals and other ancient hominins.

Key Facts

• Timeline: Neanderthals and modern humans interbred for about 7,000 years, starting 50,500 years ago.
• Genetic Impact: Neanderthal genes boosted immunity, skin pigmentation, and adaptation to harsh climates.
• Genome Deserts: Areas lacking Neanderthal genes formed rapidly, suggesting lethal gene incompatibilities.

Source: UC Berkeley

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.”

Funding: 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).

About this evolution and neuroscience research news

Author: Robert Sanders
Source: UC Berkeley
Contact: Robert Sanders – UC Berkeley
Image: The image is credited to Neuroscience News

Original Research: Closed access.
“Neandertal ancestry through time: Insights from genomes of ancient and present-day humans” by Priya Moorjani et al. Science

Abstract

Neandertal ancestry through time: Insights from genomes of ancient and present-day humans

INTRODUCTION

Gene flow from Neanderthals has shaped genetic and phenotypic variation in modern humans. Most non-Africans living today derive ~1 to 2% of their ancestry from Neanderthals.

Across the genome, some genomic regions harbor a high frequency of Neanderthal variants and are identified as “candidates of adaptive introgression,” whereas others are devoid of any Neanderthal ancestry and are referred to as “deserts.”

However, the timing and evolutionary processes, for example, genetic drift or natural selection, that have shaped the landscape of Neanderthal ancestry remain elusive. Most of the previous studies have focused on genomes of present-day individuals, where separating the effects of past demography and selection is challenging.

Ancient DNA analyses have transformed research into human evolutionary history by enabling the direct observation of genetic variation patterns that existed in the past.

RATIONALE

In this study, we analyzed genomic data from 59 ancient individuals sampled between 45,000 and 2200 years before present and 275 diverse present-day individuals to study the evolutionary history of Neanderthal ancestry throughout time.

We examined the frequency, length, and distribution of Neanderthal ancestry segments over time to answer the following questions: (i) How is Neanderthal ancestry shared among individuals, by geography and time? (ii) When did Neanderthal gene flow occur and for how long did it last? and (iii) What is the functional legacy of Neanderthal ancestry in modern humans?

RESULTS

We generated a catalog of Neanderthal ancestry in ancient and present-day modern humans and found that the majority of the Neanderthal ancestry segments are shared across populations and that the sharing of Neanderthal ancestry segments mirrors the population structure among non-Africans.

The comparison with sequenced Neanderthals, for example, Vindija, Altai, and Chagyrskaya, suggests that the gene flow occurred from a single or multiple closely related Neanderthal groups. By contrast, the earliest modern humans—Oase, Ust’-Ishim, Zlatý kůň, and Bacho Kiro—possess substantial unique Neanderthal ancestry and a distinct matching profile to the sequenced Neanderthals, indicating that some Neanderthal ancestry in these early individuals is not shared with modern humans after 40,000 years.

By studying the distribution and lengths of the Neanderthal ancestry segments in ancient individuals, we found evidence for a single extended period of Neanderthal gene flow that occurred ~47,000 years ago and lasted for ~7000 years. This is consistent with archaeological evidence for the potential overlap of early modern humans and Neanderthals in Europe.

Finally, we examined the frequency of Neanderthal ancestry across the genome and over time. We uncovered new candidates of adaptive introgression, including regions that were immediately adaptive for modern humans and some that became adaptive more recently from introgressed standing variation.

Most Neanderthal deserts—on the autosomes and the X chromosome—were formed rapidly after the gene flow and were also evident in the earliest modern human genomes. Notably, the X chromosome exhibits a nonuniform and nonrandom distribution of Neanderthal ancestry, with large Neanderthal ancestry deserts overlapping previously identified signals of sweeps in non-Africans.

CONCLUSION

Our study provides insights into the complex history of Neanderthal gene flow into modern humans. We found strong support for a single extended period of Neanderthal gene flow into the common ancestors of all non-Africans that occurred between 50,500 and 43,500 years ago. These dates provide a lower bound for the timing of the out-of-Africa migration and settlement of regions outside Africa.

The majority of natural selection—positive and negative—on Neanderthal ancestry happened very quickly after the gene flow and left clear signals in the genetic diversity of the earliest modern humans outside Africa.