Abstract

Ancient DNA makes it possible to observe natural selection directly by analysing samples from populations before, during and after adaptation events. Here we report a genome-wide scan for selection using ancient DNA, capitalizing on the largest ancient DNA data set yet assembled: 230 West Eurasians who lived between 6500 and 300 bc, including 163 with newly reported data. The new samples include, to our knowledge, the first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones, and who we show were members of the population that was the source of Europe’s first farmers. We also report a transect of the steppe region in Samara between 5600 and 300 bc, which allows us to identify admixture into the steppe from at least two external sources. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.

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Accessions

Primary accessions

European Nucleotide Archive

Data deposits

The aligned sequences are available through the European Nucleotide Archive under accession number PRJEB11450. The Human Origins genotype datasets including ancient individuals can be found at (http://genetics.med.harvard.edu/reich/Reich_Lab/Datasets.html).

References

  1. 1.

    et al. Identifying recent adaptations in large-scale genomic data. Cell 152, 703–713 (2013)

  2. 2.

    et al. Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y. Proc. Natl Acad. Sci. USA 111, 4832–4837 (2014)

  3. 3.

    et al. Genome flux and stasis in a five millennium transect of European prehistory. Nature Commun. 5, 5257 (2014)

  4. 4.

    et al. Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature 513, 409–413 (2014)

  5. 5.

    et al. Population genomics of Bronze Age Eurasia. Nature 522, 167–172 (2015)

  6. 6.

    et al. New insights into the Tyrolean Iceman’s origin and phenotype as inferred by whole-genome sequencing. Nature Commun. 3, 698 (2012)

  7. 7.

    et al. Massive migration from the steppe was a source for Indo-European languages in Europe. Nature 522, 207–211 (2015)

  8. 8.

    et al. Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European. Nature 507, 225–228 (2014)

  9. 9.

    et al. Optimal ancient DNA yields from the inner ear part of the human petrous bone. PLoS ONE 10, e0129102 (2015)

  10. 10.

    , & Fast model-based estimation of ancestry in unrelated individuals. Genome Res. 19, 1655–1664 (2009)

  11. 11.

    et al. Ancient admixture in human history. Genetics 192, 1065–1093 (2012)

  12. 12.

    et al. The phylogenetic and geographic structure of Y-chromosome haplogroup R1a. Eur. J. Hum. Genet. 23, 124–131 (2015)

  13. 13.

    The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature 526, 68–74 (2015)

  14. 14.

    & Genomic control for association studies. Biometrics 55, 997–1004 (1999)

  15. 15.

    et al. Identification of a variant associated with adult-type hypolactasia. Nature Genet. 30, 233–237 (2002)

  16. 16.

    et al. Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 74, 1111–1120 (2004)

  17. 17.

    , , , & Absence of the lactase-persistence-associated allele in early Neolithic Europeans. Proc. Natl Acad. Sci. USA 104, 3736–3741 (2007)

  18. 18.

    et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707–713 (2010)

  19. 19.

    et al. Greenlandic Inuit show genetic signatures of diet and climate adaptation. Science 349, 1343–1347 (2015)

  20. 20.

    et al. Adaptive evolution of the FADS gene cluster within Africa. PLoS ONE 7, e44926 (2012)

  21. 21.

    et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 376, 180–188 (2010)

  22. 22.

    et al. The impact of divergence time on the nature of population structure: an example from Iceland. PLoS Genet. 5, e1000505 (2009)

  23. 23.

    Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678(2007)

  24. 24.

    et al. Crohn’s disease and genetic hitchhiking at IBD5. Mol. Biol. Evol. 29, 101–111 (2012)

  25. 25.

    et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nature Genet. 40, 395–402 (2008)

  26. 26.

    et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119–124 (2012)

  27. 27.

    et al. Genetic architecture of skin and eye color in an African–European admixed population. PLoS Genet. 9, e1003372 (2013)

  28. 28.

    et al. A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am. J. Hum. Genet. 82, 424–431 (2008)

  29. 29.

    et al. Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Hum. Genet. 123, 177–187 (2008)

  30. 30.

    et al. Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet. 5, e1000562 (2009)

  31. 31.

    et al. Susceptibility to tuberculosis is associated with TLR1 polymorphisms resulting in a lack of TLR1 cell surface expression. J. Leukoc. Biol. 90, 377–388 (2011)

  32. 32.

    et al. Leprosy and the adaptation of human toll-like receptor 1. PLoS Pathog. 6, e1000979 (2010)

  33. 33.

    et al. A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness. Hum. Mol. Genet. 17, 835–843 (2008)

  34. 34.

    et al. A common variation in EDAR is a genetic determinant of shovel-shaped incisors. Am. J. Hum. Genet. 85, 528–535 (2009)

  35. 35.

    et al. Modeling recent human evolution in mice by expression of a selected EDAR variant. Cell 152, 691–702 (2013)

  36. 36.

    et al. Evidence of widespread selection on standing variation in Europe at height-associated SNPs. Nature Genet. 44, 1015–1019 (2012)

  37. 37.

    & et al. A population genetic signal of polygenic adaptation. PLoS Genet. 10, e1004412 (2014)

  38. 38.

    et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467, 832–838 (2010)

  39. 39.

    et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature Genet. 42, 937–948 (2010)

  40. 40.

    et al. Meta-analysis identifies 13 new loci associated with waist–hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nature Genet. 42, 949–960 (2010)

  41. 41.

    et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genet. 44, 981–990 (2012)

  42. 42.

    et al. Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA. Nucleic Acids Res. 38, e87 (2010)

  43. 43.

    et al. DNA analysis of an early modern human from Tianyuan Cave, China. Proc. Natl Acad. Sci. USA 110, 2223–2227 (2013)

  44. 44.

    et al. An early modern human from Romania with a recent Neanderthal ancestor. Nature. 524, 216–219 (2015)

  45. 45.

    , & ANGSD: analysis of next generation sequencing data. BMC Bioinformatics 15, 356 (2014)

  46. 46.

    International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851–861 (2007)

  47. 47.

    et al. Transcriptome and genome sequencing uncovers functional variation in humans. Nature 501, 506–511 (2013)

  48. 48.

    et al. Worldwide human relationships inferred from genome-wide patterns of variation. Science 319, 1100–1104 (2008)

  49. 49.

    et al. Inferring admixture histories of human populations using linkage disequilibrium. Genetics 193, 1233–1254 (2013)

  50. 50.

    et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. GigaScience 4 (2015)

  51. 51.

    , , & Accurate sex identification of ancient human remains using DNA shotgun sequencing. J. Archaeol. Sci. 40, 4477–4482 (2013)

  52. 52.

    et al. The sequence alignment/map format and SAMtools. Bioinformatics 25, 2078–2079 (2009)

  53. 53.

    et al. Genetic evidence for the convergent evolution of light skin in Europeans and East Asians. Mol. Biol. Evol. 24, 710–722 (2007)

  54. 54.

    et al. Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios. J. Lipid Res. 51, 2325–2333 (2010)

  55. 55.

    et al. Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genet. 5, e1000338 (2009)

  56. 56.

    et al. Genome-wide association study of circulating vitamin D levels. Hum. Mol. Genet. 19, 2739–2745 (2010)

  57. 57.

    et al. Discovery of the ergothioneine transporter. Proc. Natl Acad. Sci. USA 102, 5256–5261 (2005)

  58. 58.

    et al. ZKSCAN3 is a master transcriptional repressor of autophagy. Mol. Cell 50, 16–28 (2013)

  59. 59.

    et al. Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. Nature Genet. 43, 1082–1090 (2011)

  60. 60.

    et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26, 2336–2337 (2010)

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Acknowledgements

We thank P. de Bakker, J. Burger, C. Economou, E. Fornander, Q. Fu, F. Hallgren, K. Kirsanow, A. Mittnik, I. Olalde, A. Powell, P. Skoglund, S. Tabrizi and A. Tandon for discussions, suggestions about SNPs to include, or contribution to sample preparation or data curation. We thank S. Pääbo, M. Meyer, Q. Fu and B. Nickel for collaboration in developing the 1240k capture reagent. We thank J. M. V. Encinas and M. E. Prada for allowing us to resample La Braña 1. I.M. was supported by the Human Frontier Science Program LT001095/2014-L. C.G. was supported by the Irish Research Council for Humanities and Social Sciences (IRCHSS). F.G. was supported by a grant of the Netherlands Organization for Scientific Research, no. 380-62-005. A.K., P.K. and O.M. were supported by RFBR no. 15-06-01916 and RFH no. 15-11-63008 and O.M. by a state grant of the Ministry of Education and Science of the Russia Federation no. 33.1195.2014/k. J.K. was supported by ERC starting grant APGREID and DFG grant KR 4015/1-1. K.W.A. was supported by DFG grant AL 287 / 14-1. C.L.-F. was supported by a BFU2015-64699-P grant from the Spanish government. W.H. and B.L. were supported by Australian Research Council DP130102158. R.P. was supported by ERC starting grant ADNABIOARC (263441), and an Irish Research Council ERC support grant. D.R. was supported by US National Science Foundation HOMINID grant BCS-1032255, US National Institutes of Health grant GM100233, and the Howard Hughes Medical Institute.

Author information

Author notes

    • Cristina Gamba
    •  & Joseph Pickrell

    Present addresses: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5–7, 1350 Copenhagen, Denmark (C.G.); New York Genome Center, New York, New York 10013, USA (J.P.).

    • Wolfgang Haak
    • , Ron Pinhasi
    •  & David Reich

    These authors contributed equally to this work.

Affiliations

  1. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Iain Mathieson
    • , Iosif Lazaridis
    • , Nadin Rohland
    • , Swapan Mallick
    • , Eadaoin Harney
    • , Kristin Stewardson
    • , Joseph Pickrell
    •  & David Reich
  2. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA

    • Iosif Lazaridis
    • , Nadin Rohland
    • , Swapan Mallick
    • , Nick Patterson
    •  & David Reich
  3. Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Swapan Mallick
    • , Eadaoin Harney
    • , Kristin Stewardson
    •  & David Reich
  4. Independent researcher, Santpoort-Noord, The Netherlands

    • Songül Alpaslan Roodenberg
  5. School of Archaeology and Earth Institute, Belfield, University College Dublin, Dublin 4, Ireland

    • Daniel Fernandes
    • , Mario Novak
    • , Kendra Sirak
    • , Cristina Gamba
    •  & Ron Pinhasi
  6. Institute for Anthropological Research, Zagreb 10000, Croatia

    • Mario Novak
  7. Department of Anthropology, Emory University, Atlanta, Georgia 30322, USA

    • Kendra Sirak
  8. Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland

    • Cristina Gamba
    •  & Eppie R. Jones
  9. Australian Centre for Ancient DNA, School of Biological Sciences & Environment Institute, University of Adelaide, Adelaide, South Australia 5005, Australia

    • Bastien Llamas
    • , Alan Cooper
    •  & Wolfgang Haak
  10. Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia

    • Stanislav Dryomov
  11. Department of Paleolithic Archaeology, Institute of Archaeology and Ethnography, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia

    • Stanislav Dryomov
  12. Centro Mixto UCM-ISCIII de Evolución y Comportamiento Humanos, 28040 Madrid, Spain

    • Juan Luís Arsuaga
  13. Departamento de Paleontología, Facultad Ciencias Geológicas, Universidad Complutense de Madrid, 28040 Madrid, Spain

    • Juan Luís Arsuaga
  14. Centro Nacional de Investigacíon sobre Evolución Humana (CENIEH), 09002 Burgos, Spain

    • José María Bermúdez de Castro
  15. IPHES. Institut Català de Paleoecologia Humana i Evolució Social, Campus Sescelades-URV, 43007 Tarragona, Spain

    • Eudald Carbonell
    • , Marina Lozano
    •  & Josep Maria Vergès
  16. Area de Prehistoria, Universitat Rovira i Virgili (URV), 43002 Tarragona, Spain

    • Eudald Carbonell
    • , Marina Lozano
    •  & Josep Maria Vergès
  17. Netherlands Institute in Turkey, Istiklal Caddesi, Nur-i Ziya Sokak 5, Beyog˘ lu 34433, Istanbul, Turkey

    • Fokke Gerritsen
  18. Volga State Academy of Social Sciences and Humanities, Samara 443099, Russia

    • Aleksandr Khokhlov
    • , Pavel Kuznetsov
    •  & Oleg Mochalov
  19. State Office for Heritage Management and Archaeology Saxony-Anhalt and State Museum of Prehistory, D-06114 Halle, Germany

    • Harald Meller
    •  & Kurt W. Alt
  20. Peter the Great Museum of Anthropology and Ethnography (Kunstkamera) RAS, St Petersburg 199034, Russia

    • Vyacheslav Moiseyev
  21. Department of Prehistory and Archaeology, University of Valladolid, 47002 Valladolid, Spain

    • Manuel A. Rojo Guerra
  22. The Netherlands Institute for the Near East, Leiden RA-2300, the Netherlands

    • Jacob Roodenberg
  23. Max Planck Institute for the Science of Human History, D-07745 Jena, Germany

    • Johannes Krause
    •  & Wolfgang Haak
  24. Institute for Archaeological Sciences, University of Tübingen, D-72070 Tübingen, Germany

    • Johannes Krause
  25. Danube Private University, A-3500 Krems, Austria

    • Kurt W. Alt
  26. Institute for Prehistory and Archaeological Science, University of Basel, CH-4003 Basel, Switzerland

    • Kurt W. Alt
  27. Anthropology Department, Hartwick College, Oneonta, New York 13820, USA

    • Dorcas Brown
    •  & David Anthony
  28. Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra), 08003 Barcelona, Spain

    • Carles Lalueza-Fox

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Contributions

W.H., R.P. and D.R. supervised the study. S.A.R., J.L.A., J.M.B., E.C., F.G., A.K., P.K., M.L., H.M., O.M., V.M., M.A.R., J.R., J.M.V., J.K., A.C., K.W.A., D.B., D.A., C.L., W.H., R.P. and D.R. assembled archaeological material. I.M., I.L., N.R., S.M., N.P., S.D., J.P., W.H. and D.R. analysed genetic data. N.R., E.H., K.St., D.F., M.N., K.Si., C.G., E.R.J., B.L., C.L. and W.H. performed wet laboratory ancient DNA work. I.M., I.L. and D.R. wrote the manuscript with input from all co-authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Iain Mathieson or Wolfgang Haak or Ron Pinhasi or David Reich.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Text comprising: Archaeological context for 83 newly reported ancient samples (Section 1) and Population interactions between Anatolia, mainland Europe, and the Eurasian steppe (Section 2) with additional references.

Excel files

  1. 1.

    Supplementary Data 1

    This file contains information about 230 ancient samples used in this study.

  2. 2.

    Supplementary Data 2

    This file shows FST between ancient and modern populations.

Text files

  1. 1.

    Supplementary Data 3

    This file contains Genome-wide selection scan results and allele frequencies.

About this article

Publication history

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DOI

https://doi.org/10.1038/nature16152

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