Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe1,2,3. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet4. 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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Sequence Read Archive

Data deposits

Alignment data are available through the Sequence Read Archive (SRA) under accession numbers PRJNA230689 and SRP033596.


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The authors thank L. A. Grau Lobo (Museo de León) for access to the La Braña specimen, M. Rasmussen and H. Schroeder for valid input into the experimental work, and M. Raghavan for early access to Mal'ta genome data. Sequencing was performed at the Danish National High-Throughput DNA-Sequencing Centre, University of Copenhagen. The POPRES data were obtained from dbGaP (accession number 2038). The authors are grateful for financial support from the Danish National Research Foundation, ERC Starting Grant (260372) to TM-B, and (310372) to M.G.N., FEDER and Spanish Government Grants BFU2012-38236, the Spanish Multiple Sclerosis Netowrk (REEM) of the Instituto de Salud Carlos III (RD12/0032/0011) to A.N., BFU2011-28549 to T.M.-B., BFU2012-34157 to C.L.-F., ERC (Marie Curie Actions 300554) to M.E.A., NIH NRSA postdoctoral fellowship (F32GM106656) to C.W.K.C., NIH (R01-HG007089) to J.N., NSF postdoctoral fellowship (DBI-1103639) to M.D., the Australian NHMRC to R.A.S. and a predoctoral fellowship from the Basque Government (DEUI) to I.O.

Author information

Author notes

    • Iñigo Olalde
    •  & Morten E. Allentoft

    These authors contributed equally to this work.


  1. Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain

    • Iñigo Olalde
    • , Federico Sánchez-Quinto
    • , Gabriel Santpere
    • , Javier Prado-Martinez
    • , Juan Antonio Rodríguez
    • , Javier Quilez
    • , Oscar Ramírez
    • , Urko M. Marigorta
    • , Marcos Fernández-Callejo
    • , Tomàs Marquès-Bonet
    • , Arcadi Navarro
    •  & Carles Lalueza-Fox
  2. Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, DK-1350 Copenhagen K, Denmark

    • Morten E. Allentoft
    •  & Eske Willerslev
  3. Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA

    • Charleston W. K. Chiang
  4. Department of Integrative Biology, University of California, Berkeley, California 94720, USA

    • Michael DeGiorgio
  5. Department of Biology, Pennsylvania State University, 502 Wartik Laboratory, University Park, Pennsylvania 16802, USA

    • Michael DeGiorgio
  6. Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark

    • Simon Rasmussen
  7. I.E.S.O. 'Los Salados', Junta de Castilla y León, E-49600 Benavente, Spain

    • María Encina Prada
  8. Junta de Castilla y León, Servicio de Cultura de León, E-24071 León, Spain

    • Julio Manuel Vidal Encinas
  9. Center for Theoretical Evolutionary Genomics, University of California, Berkeley, California 94720, USA

    • Rasmus Nielsen
  10. Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity, Radboud University Nijmegen Medical Centre, 6500 Nijmegen, The Netherlands

    • Mihai G. Netea
  11. Department of Human Genetics, University of Chicago, Illinois 60637, USA

    • John Novembre
  12. Institute for Molecular Bioscience, Melanogenix Group, The University of Queensland, Brisbane, Queensland 4072, Australia

    • Richard A. Sturm
  13. Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    • Pardis Sabeti
  14. Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA

    • Pardis Sabeti
  15. Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Catalonia, Spain

    • Tomàs Marquès-Bonet
    •  & Arcadi Navarro
  16. Centre de Regulació Genòmica (CRG), Barcelona 08003, Catalonia, Spain

    • Arcadi Navarro
  17. National Institute for Bioinformatics (INB), Barcelona 08003, Catalonia, Spain

    • Arcadi Navarro


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C.L.-F. and E.W. conceived and lead the project. M.E.P. and J.M.V.E. provided anthropological and archaeological information. O.R. and M.E.A. performed the ancient extractions and library construction, respectively. I.O., M.E.A., F.S.-Q., J.P.-M., S.R., O.R., M.F.-C. and T.M.-B. performed mapping, SNP calling, mtDNA assembly, contamination estimates and different genomic analyses on the ancient genome. I.O., F.S.-Q., G.S., C.W.K.C., M.D., J.A.R., J.Q., O.R., U.M.M. and A.N. performed functional, ancestry and population genetic analyses. R.N. and J.N. coordinated the ancestry analyses. M.G.N., R.A.S. and P.S. coordinated the immunological, pigmentation and selection analyses, respectively. I.O., M.E.A., T.M.-B., E.W. and C.L.-F. wrote the majority of the manuscript with critical input from R.N., M.G.N., J.N., R.A.S., P.S. and A.N.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Eske Willerslev or Carles Lalueza-Fox.

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