Neanderthals Interbred Homosapient Europeans customizing immune system

” Neanderthals Sex-Ass-Raped Europeans customizing immune system ”

Image credits Paul Hudson / Flickr.“Is that a more pronounced inflammatory response or are you just happy to see me?”

Figure thumbnail fx1

Neanderthals Interbred Homosapient Europeans customizing immune system

  • Thousands of genes show population differences in transcriptional response to infection
  • African ancestry is associated with a stronger inflammatory response
  • Population differences in immune response are often genetically controlled
  • Natural selection contributed to ancestry-associated differences in gene regulation

Neanderthals Interbred Homosapient Europeans customizing immune system

Neanderthals Interbred Homosapient Europeans customizing immune system;   Individuals from different populations vary considerably in their susceptibility to immune-related diseases. To understand how genetic variation and natural selection contribute to these differences, we tested for the effects of African versus European ancestry on the transcriptional response of primary macrophages to live bacterial pathogens. A total of 9.3% of macrophage-expressed genes show ancestry-associated differences in the gene regulatory response to infection, and African ancestry specifically predicts a stronger inflammatory response and reduced intracellular bacterial growth. A large proportion of these differences are under genetic control: for 804 genes, more than 75% of ancestry effects on the immune response can be explained by a single cis– or trans-acting expression quantitative trait locus (eQTL). Finally, we show that genetic effects on the immune response are strongly enriched for recent, population-specific signatures of adaptation. Together, our results demonstrate how historical selective events continue to shape human phenotypic diversity today, including for traits that are key to controlling infection.

Europeans picked up a customized immune system by having sex with Neanderthals.

Sometime between one hundred to a few tens of thousands of years ago, as modern humans migrated out of Africa, they met strange peoples which weren’t completely like them, but not too different either — the Neanderthals. So, naturally, they had sex with them.

Recent years have brought along a paradigm shift when it comes to understanding our relatives, the Neanderthals and the Denisovans. Last week, a team published results showing that some areas in South-East Asia carry significant Denisovan DNA and now, another team has published a map of that DNA spread.

This map shows the proportion of the genome inferred to be Denisovan in ancestry in diverse non-Africans. The color scale is not linear to allow saturation of the high Denisova proportions in Oceania (bright red) and better visualization of the peak of Denisova proportion in South Asia. Credits: Sankararaman et al./Current Biology 2016

Neanderthals Interbred Homosapient Europeans customizing immune system;   This map shows the proportion of the genome inferred to be Denisovan in ancestry in diverse non-Africans. The color scale is not linear to allow saturation of the high Denisova proportions in Oceania (bright red) and better visualization of the peak of Denisova proportion in South Asia. Credits: Sankararaman et al./Current Biology 2016.We know quite a bit about Neanderthal DNA, although anthropologists have had to rehash some of their theories. Most notably, not only did humans and Neanderthals interbreed, but they did so much earlier than previously thought. It was first shown that humans interbred with Neanderthals  100,000 years-ago and then 50,000 years-ago. OK, so where do Denisovans fit into this picture?

Neanderthals Interbred Homosapient Europeans customizing immune system;   Denisovans are an extinct species of human in the genus Homo. In March 2010, scientists announced the discovery of a finger bone fragment of a juvenile female who lived about 41,000 years ago. The remains were found in the remote Denisova Cave in the Altai Mountains, Siberia, a cave which has also been inhabited by Neanderthals and modern humans. DNA studies confirmed this was a new species, related to Neanderthals but ultimately different. However, while Neanderthal DNA is common in most non-African humans, Denisovan DNA is much more elusive. There is a notable exception however: the inhabitants of Melanesia, a subregion of Oceania, have between 4% and 6% Denisovan DNA.

This is intriguing because it shows that even though the remains of Denisovans were found in Siberia, the only people with significant Denisovan DNA live in Melanesia – so humans interbred with Denisovans somewhere in that area (or their descendants did).

“There are certain classes of genes that modern humans inherited from the archaic humans with whom they interbred, which may have helped the modern humans to adapt to the new environments in which they arrived,” says senior author David Reich, a geneticist at Harvard Medical School and the Broad Institute. “On the flip side, there was negative selection to systematically remove ancestry that may have been problematic from modern humans. We can document this removal over the 40,000 years since these admixtures occurred.”

Neanderthals Interbred Homosapient Europeans customizing immune system;   They found that individuals from Oceania possess by far the highest percentage of archaic ancestry, while only south-east Asians have significant Denisovan ancestry (and again, more than previously believed). When you consider that most people today have some Neanderthal DNA, but people of African descent don’t, you end up with a pretty complicated problem.

“The interactions between modern humans and archaic humans are complex and perhaps involved multiple events,” Reich says.

Neanderthals Interbred Homosapient Europeans customizing immune system;   The genes we acquired in that exchange may be responsible for a whole range of diseases, but it’s possible they gave our ancestors the means to better adapt to their new environment. Scientists studying the immune system of humans today have found that people of European descent have significantly different immune responses from their African counterparts — a direct consequence of the exchange, they believe. The finding could explain why Africans generally have more robust immune systems than Europeans, but also why they’re more predisposed to certain autoimmune conditions.

“I was expecting to see ancestry-associated differences in immune response but not such a clear trend towards an overall stronger response to infection among individuals of African descent,” says University of Montreal geneticist and paper co-author Luis Barreiro.

Neanderthals Interbred Homosapient Europeans customizing immune system;   Barreiro’s team examined samples taken from 175 American patients, roughly half and half of African and European ancestry. They extracted macrophages from their blood — white cells that kill pathogens by “eating” them — and infected the cells with Listeria and Salmonella. They let them go about their business for 24 hours, then analyzed them.

The cells retrieved from the African group had reduced the bacterial growth three times faster than the European group thanks to a stronger inflammatory response. That’s a definite plus when combating infections, but the team points out it’s a double edged sword.

“The immune system of African Americans responds differently, but we cannot conclude that it is better,” Barreiro said, “since a stronger immune response also has negative effects, including greater susceptibility to autoimmune inflammatory diseases such as Crohn’s disease.”

Neanderthals Interbred Homosapient Europeans customizing immune system;   The team also examined the genetic makeup of the cells’ active genes, and found a link between the European sample and Neanderthal DNA — but didn’t find any similar link in the African sample. The team says that when early humans migrated into Europe around 100,000 years ago, they encountered a continent already colonized by the Neanderthal. Finding traces of their DNA in modern European subjects suggests that the two species actively bred with each other. It makes sense, too. The new genes would have offered our ancestors an evolutionary edge in Europe, where environmental conditions were very different from those in Africa. A lower inflammatory response would also make more sense in the colder climate compared to Africa’s sweltering heat, which promotes infections.

“Our results suggest that the immune systems of African- and European-descended individuals have evolved to better respond to the specific needs imposed by their specific environments,” Barreiro told Live Science.

“What is advantageous in one context is likely to be detrimental in another.”

Too much of a good thing:
Neanderthals Interbred Homosapient Europeans customizing immune system;

Neanderthals Interbred Homosapient Europeans customizing immune system;   A separate study also found a lower inflammatory tendency in monocytes against bacterial and viral threats in people of European descent compared to those from Africa. The study included 200 participants from France. The team, led by Lluis Quintana-Murci from the Institut Pasteur, also tied the differences to Neanderthal-like genes in the European participants. In broad lines, the results are the same. The French team also suggests that a powerful inflammatory response could actually be dangerous in Europe, so this effect could have provided an inherent evolutionary benefit — weeding out the more inflammatory-prone genes over time.

“Reducing immune inflammatory responses is a way to avoid autoimmunity, inflammatory, and allergic reactions,” Quintana-Murci told ResearchGate.

“Finding that reduced immune responses has conferred an advantage highlights the tradeoff between recognising pathogens while avoiding exacerbated, aberrant reactions that can be also harmful for the host.”

Both studies say more work needs to be done before we understand where these differences stem from. But it could help us develop things like personalized treatments or medications tailored for certain ethnicities’ needs.

“There is still much to do,” says Barreiro. “[Genetics] explains only about 30 percent of the observed differences in immune responses. Our future studies should focus on other factors, emphasising the influence of the environment and our behaviour.”

Barreiro’s and Quintana-Murci’s studies are published in the journal Cell.

Genome sequence of a 45,000-year-old modern human from western Siberia:
Neanderthals Interbred Homosapient Europeans customizing immune system;

(23 October 2014)
15 May 2014
29 August 2014
Published online
22 October 2014


Neanderthals Interbred Homosapient Europeans customizing immune system;   We present the high-quality genome sequence of a ~45,000-year-old modern human male from Siberia. This individual derives from a population that lived before—or simultaneously with—the separation of the populations in western and eastern Eurasia and carries a similar amount of Neanderthal ancestry as present-day Eurasians. However, the genomic segments of Neanderthal ancestry are substantially longer than those observed in present-day individuals, indicating that Neanderthal gene flow into the ancestors of this individual occurred 7,000–13,000 years before he lived. We estimate an autosomal mutation rate of 0.4 × 10−9 to 0.6 × 10−9 per site per year, a Y chromosomal mutation rate of 0.7 × 10−9 to 0.9 × 10−9 per site per year based on the additional substitutions that have occurred in present-day non-Africans compared to this genome, and a mitochondrial mutation rate of 1.8 × 10−8 to 3.2 × 10−8 per site per year based on the age of the bone.

At a glance



  1. Geographic location, morphology and dating.
    Figure 1
  2. Principal Components (PC) analysis exploring the relationship of Ust/
    Figure 2
  3. Statistics testing whether the Ust/
    Figure 3
  4. Inferred population size changes over time.
    Figure 4
  5. Regions of Neanderthal ancestry on chromosome 12 in the Ust/
    Figure 5
  6. Dating the Neandertal admixture in Ust/
    Figure 6


Accession codes

Primary accessions

European Nucleotide Archive

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Author information:
Neanderthals Interbred Homosapient Europeans customizing immune system;  


  1. Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, IVPP, CAS, Beijing 100044, China

    • Qiaomei Fu
  2. Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany

    • Qiaomei Fu,
    • Ayinuer Aximu-Petri,
    • Kay Prüfer,
    • Cesare de Filippo,
    • Matthias Meyer,
    • Michael Lachmann,
    • Janet Kelso,
    • T. Bence Viola &
    • Svante Pääbo
  3. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA

    • Heng Li,
    • Priya Moorjani &
    • David Reich
  4. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Heng Li &
    • David Reich
  5. Department of Biological Sciences, Columbia University, New York, New York 10027, USA

    • Priya Moorjani
  6. Department of Integrative Biology, University of California, Berkeley, California 94720-3140, USA

    • Flora Jay &
    • Montgomery Slatkin
  7. Institute for Problems of the Development of the North, Siberian Branch of the Russian Academy of Sciences, Tyumen 625026, Russia

    • Sergey M. Slepchenko &
    • Dmitry I. Razhev
  8. Expert Criminalistics Center, Omsk Division of the Ministry of Internal Affairs, Omsk 644007, Russia

    • Aleksei A. Bondarev
  9. Department of Biology, Emory University, Atlanta, Georgia 30322, USA

    • Philip L. F. Johnson
  10. Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany

    • Nicolas Zwyns,
    • Domingo C. Salazar-García,
    • Michael P. Richards,
    • Jean-Jacques Hublin &
    • T. Bence Viola
  11. Department of Anthropology, University of California, Davis, California 95616, USA

    • Nicolas Zwyns
  12. Department of Archaeology, University of Cape Town, Cape Town 7701, South Africa

    • Domingo C. Salazar-García
  13. Departament de Prehistòria i Arqueologia, Universitat de València, Valencia 46010, Spain

    • Domingo C. Salazar-García
  14. Research Group on Plant Foods in Hominin Dietary Ecology, Max-Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany

    • Domingo C. Salazar-García
  15. Institute of Geology and Mineralogy, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia

    • Yaroslav V. Kuzmin &
    • Susan G. Keates
  16. Institute of Plant and Animal Ecology, Urals Branch of the Russian Academy of Sciences, Yekaterinburg 620144, Russia

    • Pavel A. Kosintsev
  17. Laboratory of Archaeology, Department of Anthropology, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada

    • Michael P. Richards
  18. Siberian Cultural Center, Omsk 644010, Russia

    • Nikolai V. Peristov
  19. Santa Fe Institute, Santa Fe, New Mexico 87501, USA

    • Michael Lachmann
  20. Oxford Radiocarbon Accelerator Unit, Research Laboratory for Archaeology and the History of Art, University of Oxford, Oxford OX1 3QY, UK

    • Katerina Douka &
    • Thomas F. G. Higham
  21. Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA

    • David Reich


Q.F., S.M.S., A.A.B., Y.V.K., J.K., T.B.V. and S.P. designed the research. A.A.P. and Q.F. performed the experiments; Q.F., H.L., P.M., F.J., P.L.F.J., K.P., C.d.F., M.M., M.L., M.S., D.R., J.K. and S.P. analysed genetic data; K.D. and T.F.G.H. performed 14C dating; D.C.S.-G. and M.P.R. analysed stable isotope data; N.V.P., P.A.K. and D.I.R. contributed samples and data; S.M.S., A.A.B., N.Z., Y.V.K., S.G.K., J.-J.H. and T.B.V. analysed archaeological and anthropological data; Q.F., J.K., T.B.V. and S.P. wrote and edited the manuscript with input from all authors.

Competing financial interests

The authors declare no competing financial interests.

Corresponding authors:
Neanderthals Interbred Homosapient Europeans customizing immune system;

Correspondence to:

All sequence data have been submitted to the European Nucleotide Archive (ENA) and are available under the following Ust’-Ishim accession number: PRJEB6622. The data from the 25 present-day human genomes are available from ( and from (

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