Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European
Open accessAbstract
Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet. However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Braña-Arintero site in León, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Braña individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer.
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Western hunter-gatherers of central and southern European populations survived in Palaeolithic Europe with dark skin pigmentation.
“However, western hunter-gatherers of central and southern European populations survived in Palaeolithic Europe with dark skin pigmentation [44, 45]”
From Ancient DNA and the rewriting of human history: be sparing with Occam’s razor (2016) · cites this paper as [45]
aDNA from Mesolithic Europeans shows that adaptive variants associated with pathogen resistance in modern populations were already present in hunter-gatherers before the advent of agriculture.
“aDNA from Mesolithic Europeans shows, however, that adaptive variants associated with pathogen resistance in modern populations were already present in hunter-gatherers before the advent of agriculture [45].”
From Ancient DNA and the rewriting of human history: be sparing with Occam’s razor (2016) · cites this paper as [45]
Both SLC24A5 and SLC45A2 exhibited an ancestral homozygous state in Mesolithic specimens of Central and Western Europe, while SLC24A5 had the derived state in a Central European Neolithic individual.
“Both SLC24A5 and SLC45A2 exhibited an ancestral homozygous state in Mesolithic specimens of Central5 and Western Europe7, while SLC24A5 had the derived state in a Central European Neolithic individual5.”
From Genome flux and stasis in a five millennium transect of European prehistory (2014) · cites this paper as [7]
Most aDNA studies indicate that Upper Paleolithic and many Mesolithic West Eurasian individuals carried relatively few light skin pigmentation-associated alleles that are common in present-day Europeans.
“Although AMH entered Europe by at least ∼43 kya, most aDNA studies indicate that Upper Paleolithic and many Mesolithic West Eurasian individuals carried relatively few light skin pigmentation-associated alleles that are common in present-day Europeans ( Olalde et al., 2014 ).”
From The genetic architecture of human skin pigmentation: evolution and adaptation across global populations (2026) · cites this paper as Olalde et al., 2014
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- Authors
- Olalde, I., Allentoft, M. E., Sánchez-Quinto, F., Santpere, G., Chiang, C. W. K., DeGiorgio, M., Prado-Martinez, J., Rodríguez, J. A., Rasmussen, S., Quilez, J., Ramírez, O., Marigorta, U. M., Fernández-Callejo, M., Prada, M. E., Encinas, J. M. V., Nielsen, R., Netea, M. G., Novembre, J., Sturm, R. A., Sabeti, P., Marquès-Bonet, T., Navarro, A., Willerslev, E., & Lalueza-Fox, C.
- Affiliations
- University of Copenhagen (DK)
- Consejo Superior de Investigaciones Científicas (ES)
- University of California, Los Angeles (US)
- Pennsylvania State University (US)
- Technical University of Denmark (DK)
- Junta de Castilla y León (ES)
- University of California, Berkeley (US)
- Radboud University Nijmegen (NL)
- University of Chicago (US)
- The University of Queensland (AU)
- Broad Institute (US)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Willerslev, Eske
- ORCID
- Allentoft, Morten E.
- Santpere, Gabriel
- Chiang, Charleston W. K.
- Prado-Martinez, Javier
- Rodríguez, Juan Antonio
- Rasmussen, Simon
- Quilez, Javier
- Marigorta, Urko M.
- Fernández-Callejo, Marcos
- Encinas, Julio Manuel Vidal
- Nielsen, Rasmus
- Netea, Mihai G.
- Novembre, John
- Sturm, Richard A.
- Sabeti, Pardis
- Navarro, Arcadi
- Willerslev, Eske
- Venue
- Nature
- Published
- 2014-01-26
- Volume
- 507
- Issue
- 7491
- Pages
- 225-228
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4269527
- OpenAlex
- W1964332640
- Cited by
- 360
- References
- 30
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 34 · 2023: 14 · 2022: 27 · 2021: 22 · 2020: 23 · 2019: 30 · 2018: 32 · 2017: 40 · 2016: 30 · 2015: 40 · 2014: 31
- FWCI
- 30.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Griffith Research Online (submittedVersion)
- Funders
- Lundbeckfonden (R109-2012-9995, R70-2010-6286, R155-2013-16338, R38-2008-3048, R24-2008-2527)
- National Human Genome Research Institute (R01HG007089)
- National Institute of General Medical Sciences (F32GM106656)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Social Sciences › Arts and Humanities › Archeology › Paleopathology and ancient diseases
- Keywords
- hunter-gatherers, eye color, lactose intolerance, starch hydrolysis, pathogen resistance, immune-related genes, Neolithic transition, ancient DNA
- MeSH terms
- Agriculture, Alleles, Biological Evolution, Eye Color, Fossils, Humans, Immunity, Lactose Intolerance, Male, Pigmentation, Skeleton, Skin Pigmentation, Spain, Genome, Human, Polymorphism, Single Nucleotide, Genomics, Principal Component Analysis, White People, History, Ancient, Caves
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