Ancient human genomes suggest three ancestral populations for present-day Europeans (original) (raw)

Accession codes

Primary accessions

European Nucleotide Archive

Data deposits

The aligned sequences are available through the European Nucleotide Archive under accession number PRJEB6272. The fully public version of the Human Origins dataset can be found at (http://genetics.med.harvard.edu/reichlab/Reich_Lab/Datasets.html). The full version of the dataset (including additional samples) is available to researchers who send a signed letter to D.R. indicating that they will abide by specified usage conditions (Supplementary Information section 9).

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Acknowledgements

We thank the 1,615 volunteers from 147 diverse populations who donated DNA samples and whose genetic data are newly reported in this study. We are grateful to C. Beall, N. Bradman, A. Gebremedhin, D. Labuda, M. Nelis and A. Di Rienzo for sharing DNA samples; to D. Weigel, C. Lanz, V. Schünemann, P. Bauer and O. Riess for support and access to DNA sequencing facilities; to P. Johnson for advice on contamination estimation; to G. Hellenthal for help with the ChromoPainter software; and to P. Skoglund for sharing graphics software. We thank K. Nordtvedt for alerting us to newly discovered Y-chromosome SNPs. We downloaded the POPRES data from dbGaP at (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000145.v4.p2) through dbGaP accession number phs000145.v1.p2. We thank all the volunteers who donated DNA. We thank the staff of the Unità Operativa Complessa di Medicina Trasfusionale, Azienda Ospedaliera Umberto I, Siracusa, Italy for assistance in sample collection; and The National Laboratory for the Genetics of Israeli Populations for facilitating access to DNA. We thank colleagues at the Applied Genomics at the Children’s Hospital of Philadelphia, especially H. Hakonarson, C. Kim, K. Thomas, and C. Hou, for genotyping samples on the Human Origins array. J.Kr., A.M. and C.P. are grateful for support from DFG grant number KR 4015/1-1, the Carl-Zeiss Foundation and the Baden Württemberg Foundation. S.P., G.R., Q.F., C.F., K.P., S.C. and J.Ke. acknowledge support from the Presidential Innovation Fund of the Max Planck Society. G.R. was supported by an NSERC fellowship. J.G.S. acknowledges use of the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by NSF grant number OCI-1053575. E.B. and O.B. were supported by RFBR grants 13-06-00670, 13-04-01711, 13-04-90420 and by the Molecular and Cell Biology Program of the Presidium, Russian Academy of Sciences. B.M. was supported by grants OTKA 73430 and 103983. A.Saj. was supported by a Finnish Professorpool (Paulo Foundation) Grant. The Lithuanian sampling was supported by the LITGEN project (VP1-3.1-ŠMM-07-K-01-013), funded by the European Social Fund under the Global Grant Measure. A.S. was supported by Spanish grants SAF2011-26983 and EM 2012/045. O.U. was supported by Ukrainian SFFS grant F53.4/071. S.A.T. was supported by NIH Pioneer Award 8DP1ES022577-04 and NSF HOMINID award BCS-0827436. K.T. was supported by an Indian CSIR Network Project (GENESIS: BSC0121). L.S. was supported by an Indian CSIR Bhatnagar Fellowship. R.V., M.M., J.P. and E.M. were supported by the European Union Regional Development Fund through the Centre of Excellence in Genomics to the Estonian Biocentre and University of Tartu and by an Estonian Basic Research grant SF0270177As08. M.M. was additionally supported by Estonian Science Foundation grant number 8973. J.G.S. and M.S. were supported by NIH grant GM40282. P.H.S. and E.E.E. were supported by NIH grants HG004120 and HG002385. D.R. and N.P. were supported by NSF HOMINID award BCS-1032255 and NIH grant GM100233. D.R. and E.E.E. are Howard Hughes Medical Institute investigators. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

Author information

Author notes

  1. Theologos Loukidis & Lalji Singh
    Present address: Present addresses: Amgen, 33 Kazantzaki Str, Ilioupolis 16342, Athens, Greece (T.L.); Banaras Hindu University, Varanasi 221 005, India (L.S.).,
  2. Ruslan Ruizbakiev: Deceased.

Authors and Affiliations

  1. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Iosif Lazaridis, Swapan Mallick, Qiaomei Fu, Susanne Nordenfelt, Heng Li, Nadin Rohland & David Reich
  2. Broad Institute of Harvard and MIT, Cambridge, 02142, Massachusetts, USA
    Iosif Lazaridis, Nick Patterson, Swapan Mallick, Bonnie Berger, Susanne Nordenfelt, Heng Li, Nadin Rohland & David Reich
  3. Institute for Archaeological Sciences, University of Tübingen, Tübingen, 72074, Germany
    Alissa Mittnik, Kirsten I. Bos, Cosimo Posth & Johannes Krause
  4. Max Planck Institute for Evolutionary Anthropology, Leipzig, 04103, Germany
    Gabriel Renaud, Sergi Castellano, Qiaomei Fu, Cesare de Filippo, Kay Prüfer, Susanna Sawyer, Matthias Meyer, Svante Pääbo & Janet Kelso
  5. Institute of Anthropology, Johannes Gutenberg University Mainz, Mainz D-55128, Germany.,
    Karola Kirsanow, Ruth Bollongino & Joachim Burger
  6. Department of Genome Sciences, University of Washington, Seattle, Washington, 98195, USA
    Peter H. Sudmant, Joshua G. Schraiber & Evan E. Eichler
  7. Department of Integrative Biology, University of California, Berkeley, 94720-3140, California, USA
    Joshua G. Schraiber, William Klitz & Montgomery Slatkin
  8. Department of Mathematics and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA
    Mark Lipson & Bonnie Berger
  9. Archaeological Research Laboratory, Stockholm University, 114 18, Sweden.,
    Christos Economou
  10. Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, IVPP, CAS, Beijing 100049, China.,
    Qiaomei Fu
  11. Australian Centre for Ancient DNA and Environment Institute, School of Earth and Environmental Sciences, University of Adelaide, Adelaide, 5005, South Australia, Australia
    Wolfgang Haak & Alan Cooper
  12. The Cultural Heritage Foundation, Västerås 722 12, Sweden.,
    Fredrik Hallgren & Elin Fornander
  13. National Museum of Natural History, L-2160, Luxembourg.,
    Dominique Delsate & Jean-Michel Guinet
  14. National Center of Archaeological Research, National Museum of History and Art, L-2345, Luxembourg.,
    Dominique Delsate
  15. Department of Paleoanthropology, Senckenberg Center for Human Evolution and Paleoenvironment, University of Tübingen, Tübingen D-72070, Germany.,
    Michael Francken
  16. State Office for Cultural Heritage Management Baden-Württemberg, Osteology, Konstanz D-78467, Germany.,
    Joachim Wahl
  17. Center for Global Health and Child Development, Kisumu 40100, Kenya.,
    George Ayodo
  18. Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK.,
    Hamza A. Babiker
  19. Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Alkhod, Muscat 123, Oman.,
    Hamza A. Babiker
  20. Laboratorio de Genética Molecular Poblacional, Instituto Multidisciplinario de Biología Celular (IMBICE), CCT-CONICET & CICPBA, La Plata, B1906APO, Argentina.,
    Graciela Bailliet & Claudio M. Bravi
  21. Research Centre for Medical Genetics, Moscow 115478, Russia.,
    Elena Balanovska & Oleg Balanovsky
  22. Vavilov Institute for General Genetics, Moscow 119991, Russia.,
    Oleg Balanovsky
  23. Escuela de Biología, Universidad de Costa Rica, San José 2060, Costa Rica.,
    Ramiro Barrantes
  24. Institute of Biology, Research group GENMOL, Universidad de Antioquia, Medellín, Colombia
    Gabriel Bedoya
  25. Rambam Health Care Campus, Haifa 31096, Israel.,
    Haim Ben-Ami
  26. Department of Medical Genetics and Szentagothai Research Center, University of Pécs, Pécs H-7624, Hungary.,
    Judit Bene & Béla Melegh
  27. Al Akhawayn University in Ifrane (AUI), School of Science and Engineering, Ifrane 53000, Morocco.,
    Fouad Berrada
  28. Forensic Genetics Laboratory, Institute of Legal Medicine, Università Cattolica del Sacro Cuore, Rome 00168, Italy.,
    Francesca Brisighelli
  29. Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.,
    George B. J. Busby & Cristian Capelli
  30. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.,
    George B. J. Busby
  31. Laboratorio di Genetica Molecolare, IRCCS Associazione Oasi Maria SS, Troina 94018, Italy.,
    Francesco Cali
  32. Belgorod State University, Belgorod 308015, Russia.,
    Mikhail Churnosov
  33. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L5, Canada.,
    David E. C. Cole
  34. Servicio de Huellas Digitales Genéticas, School of Pharmacy and Biochemistry, Universidad de Buenos Aires, 1113 CABA, Argentina.,
    Daniel Corach
  35. Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.,
    Larissa Damba, Marina Gubina, Ludmila Osipova, Olga Posukh & Mikhail Voevoda
  36. Institute of Linguistics, University of Bern, Bern CH-3012, Switzerland.,
    George van Driem
  37. Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Russian Academy of Science, Siberian Branch, Novosibirsk 630090, Russia.,
    Stanislav Dryomov, Elena B. Starikovskaya & Rem Sukernik
  38. Anthropologie Moléculaire et Imagerie de Synthèse, CNRS UMR 5288, Université Paul Sabatier Toulouse III, Toulouse 31000, France.,
    Jean-Michel Dugoujon
  39. North-Eastern Federal University and Yakut Research Center of Complex Medical Problems, Yakutsk 677013, Russia.,
    Sardana A. Fedorova
  40. Department of Human Genetics, University of Chicago, Chicago, 60637, Illinois, USA
    Irene Gallego Romero & Aashish R. Jha
  41. ARL Division of Biotechnology, University of Arizona, Tucson, 85721, Arizona, USA
    Michael Hammer
  42. Department of Ecology and Evolution, Stony Brook University, Stony Brook, New York 11794, USA.,
    Brenna M. Henn
  43. Department of Clinical Science, University of Bergen, Bergen 5021, Norway.,
    Tor Hervig
  44. NextBio, Illumina, Santa Clara, California 95050, USA.,
    Ugur Hodoglugil
  45. Department of Medical Genetics, National Human Genome Center, Medical University Sofia, Sofia 1431, Bulgaria.,
    Sena Karachanak-Yankova, Desislava Nesheva & Draga Toncheva
  46. Institute of Biochemistry and Genetics, Ufa Research Centre, Russian Academy of Sciences, Ufa 450054, Russia.,
    Rita Khusainova, Elza Khusnutdinova & Sergey Litvinov
  47. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa 450074, Russia.,
    Rita Khusainova, Elza Khusnutdinova & Sergey Litvinov
  48. College of Medicine, University of Arizona, Tucson, 85724, Arizona, USA
    Rick Kittles
  49. Division of Biological Anthropology, University of Cambridge, Cambridge CB2 1QH, UK.,
    Toomas Kivisild
  50. Department of Human and Medical Genetics, Vilnius University, Vilnius LT-08661, Lithuania.,
    Vaidutis Kučinskas & Ingrida Uktveryte
  51. Estonian Biocentre, Evolutionary Biology group, Tartu, 51010, Estonia.,
    Alena Kushniarevich, Sergey Litvinov, Hovhannes Sahakyan, Richard Villems & Mait Metspalu
  52. Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.,
    Leila Laredj
  53. Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.,
    Theologos Loukidis, Mark G. Thomas & Andres Ruiz-Linares
  54. Gladstone Institutes, San Francisco, 94158, California, USA
    Robert W. Mahley
  55. Department of Evolutionary Biology, University of Tartu, Tartu 51010, Estonia.,
    Ene Metspalu, Jüri Parik & Richard Villems
  56. Centro de Investigaciones Biomédicas de Guatemala, Ciudad de Guatemala, Guatemala.,
    Julio Molina
  57. Research Department, 23andMe, Mountain View, California 94043, USA.,
    Joanna Mountain
  58. Cultural Anthropology Program, University of Oulu, Oulu 90014, Finland.,
    Klemetti Näkkäläjärvi
  59. Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam 65001, Tanzania.,
    Thomas Nyambo
  60. Research Institute of Health, North-Eastern Federal University, Yakutsk 677000, Russia.,
    Fedor Platonov
  61. Dipartimento di Fisica e Chimica, Università di Palermo, Palermo 90128, Italy.,
    Valentino Romano
  62. Instituto de Alta Investigación, Universidad de Tarapacá, Arica 1000000, Chile.,
    Francisco Rothhammer
  63. Programa de Genética Humana ICBM Facultad de Medicina Universidad de Chile, Santiago 8320000, Chile.,
    Francisco Rothhammer
  64. Centro de Investigaciones del Hombre en el Desierto, Arica 1000000, Chile.,
    Francisco Rothhammer
  65. Centre for Population Health Sciences, The University of Edinburgh Medical School, Edinburgh EH8 9AG, UK.,
    Igor Rudan
  66. Institute of Immunology, Academy of Science, Tashkent 70000, Uzbekistan.,
    Ruslan Ruizbakiev
  67. Laboratory of Ethnogenomics, Institute of Molecular Biology, National Academy of Sciences of Armenia, Yerevan 0014, Armenia.,
    Hovhannes Sahakyan & Levon Yepiskoposyan
  68. Department of Forensic Medicine, Hjelt Institute, University of Helsinki, Helsinki 00014, Finland.,
    Antti Sajantila
  69. Department of Molecular and Medical Genetics, Institute of Applied Genetics, University of North Texas Health Science Center, Fort Worth, 76107, Texas, USA
    Antti Sajantila
  70. Departamento de Anatomía Patolóxica e Ciencias Forenses, Unidade de Xenética, and Instituto de Ciencias Forenses, Grupo de Medicina Xenómica (GMX), Facultade de Medicina, Universidade de Santiago de Compostela, Galcia 15872, Spain.,
    Antonio Salas
  71. Research Fellow, Henry Stewart Group, Russell House, London WC1A 2HN, UK.,
    Ayele Tarekegn
  72. Institute of Bioorganic Chemistry Academy of Sciences Republic of Uzbekistan, Tashkent 100125, Uzbekistan.,
    Shahlo Turdikulova
  73. Department of Genetics and Cytology, V. N. Karazin Kharkiv National University, Kharkiv 61077, Ukraine.,
    Olga Utevska
  74. Instituto Boliviano de Biología de la Altura, Universidad Mayor de San Andrés, 591 2 La Paz, Bolivia.,
    René Vasquez & Mercedes Villena
  75. UniversidadAutonoma Tomás Frías, Potosí, Bolivia
    René Vasquez & Mercedes Villena
  76. Institute of Internal Medicine, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk 630089, Russia.,
    Mikhail Voevoda
  77. Novosibirsk State University, Novosibirsk 630090, Russia.,
    Mikhail Voevoda
  78. Basic Research Laboratory, NCI, NIH, Frederick National Laboratory, Leidos Biomedical, Frederick, Maryland 21702, USA.,
    Cheryl A. Winkler
  79. Lebanese American University, School of Medicine, Beirut 13-5053, Lebanon.,
    Pierre Zalloua
  80. Harvard School of Public Health, Boston, 02115, Massachusetts, USA
    Pierre Zalloua
  81. Department of Medical Biology, University of Split, School of Medicine, Split 21000, Croatia.,
    Tatijana Zemunik
  82. Department of Biology and Genetics, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA
    Sarah A. Tishkoff
  83. CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India.,
    Lalji Singh & Kumarasamy Thangaraj
  84. Estonian Academy of Sciences, Tallinn 10130, Estonia.,
    Richard Villems
  85. Institut de Biologia Evolutiva (CSIC-UPF), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona 08003, Spain.,
    David Comas
  86. Howard Hughes Medical Institute, University of Washington, Seattle, 98195, Washington, USA
    Evan E. Eichler
  87. Howard Hughes Medical Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA
    David Reich
  88. Senckenberg Centre for Human Evolution and Palaeoenvironment, University of Tübingen, 72070 Tübingen, Germany.,
    Johannes Krause
  89. Max Planck Institut für Geschichte und Naturwissenschaften, Jena 07745, Germany.,
    Johannes Krause

Authors

  1. Iosif Lazaridis
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  2. Nick Patterson
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Contributions

B.B., E.E.E., J.Bu., M.S., S.P., J.Ke., D.R. and J.Kr. supervised the study. I.L., N.P., A.M., G.R., S.M., K.K., P.H.S., J.G.S., S.C., M.L., Q.F., H.L., C.dF., K.P., W.H., M.Met., M.Mey. and D.R. analysed genetic data. F.H., E.F., D.D., M.F., J.-M.G., J.W., A.C. and J.Kr. obtained human remains. A.M., C.E., R.Bo., K.I.B., S.S., C.P., N.R. and J.Kr. processed ancient DNA. I.L., N.P., S.N., N.R., G.A., H.A.B., G.Ba., E.B., O.B., R.Ba., G.Be., H.B.-A., J.Be., F.Be., C.M.B., F.Br., G.B.J.B., F.C., M.C., D.E.C.C., D.Cor., L.D., G.vD., S.D., J.-M.D., S.A.F., I.G.R., M.G., M.H., B.M.H., T.H., U.H., A.R.J., S.K.-Y., R.Kh., E.K., R.Ki., T.K., W.K., V.K., A.K., L.L., S.L., T.L., R.W.M., B.M., E.M., J.Mol., J.Mou., K.N., D.N., T.N., L.O., J.P., F.P., O. P., V.R., F.R., I.R., R.R., H.S., A.Saj., A.Sal., E.B.S., A.Tar., D.T., S.T., I.U., O.U., R.Va., M.Vi., M.Vo., C.A.W., L.Y., P.Z., T.Z., C.C., M.G.T., A.R.-L., S.A.T., L.S., K.T., R.Vi., D.Com., R.S., M.Met., S.P. and D.R. assembled the genotyping dataset. I.L., N.P., D.R. and J.Kr. wrote the manuscript with help from all co-authors.

Corresponding authors

Correspondence toDavid Reich or Johannes Krause.

Ethics declarations

Competing interests

U.H. is an employee of Illumina, T.L. is an employee of Amgen, and J.M. is an employee of 23andMe.

Extended data figures and tables

Extended Data Figure 1 Photographs of analysed ancient samples.

a, Loschbour skull. b, Stuttgart skull, missing the lower right M2 we sampled. c, Excavation at Kanaljorden in Motala, Sweden. d, Motala 1 in situ.

Extended Data Figure 2 Pairwise sequential Markovian coalescent (PSMC) analysis.

a, Inference of population size as a function of time, showing a very small recent population size over the most recent period in the ancestry of Loschbour (at least the last 5–10 thousand years). b, Inferred time since the most recent common ancestor from the PSMC for chromosomes 20, 21, 22 (top to bottom); Stuttgart is plotted on top and Loschbour at bottom.

Extended Data Figure 3 ADMIXTURE analysis (K = 2 to K = 20).

Ancient samples (Loschbour, Stuttgart, Motala_merge, Motala12, MA1, and LaBraña) are on the left.

Extended Data Figure 4 ANE ancestry is present in both Europe and the Near East but WHG ancestry is restricted to Europe, which cannot be due to a single admixture event.

On the x axis we present the statistic _f_4(Test, Stuttgart; MA1, Chimp), which measures where MA1 shares more alleles with a test population than with Stuttgart. It is positive for most European and Near Eastern populations, consistent with ANE (MA1-related) gene flow into both regions. On the y axis we present the statistic _f_4(Test, Stuttgart; Loschbour, Chimp), which measures whether Loschbour shares more alleles with a test sample than with Stuttgart. Only European populations show positive values of this statistic, providing evidence of WHG (Loschbour-related) admixture only in Europeans.

Extended Data Figure 5 MA1 is the best surrogate for ANE for which we have data.

Europeans share more alleles with MA1 than with Karitiana, as we see from the fact that in a plot of _f_4(Test, BedouinB; MA1, Chimp) and _f_4(Test, BedouinB; Karitiana, Chimp), the European cline deviates in the direction of MA1, rather than Karitiana (the slope is > 1 and European populations are above the line indicating inequality of these two statistics).

Extended Data Figure 6 The differential relatedness of west Eurasians to Stuttgart (EEF), Loschbour (WHG), and MA1 (ANE) cannot be explained by two-way mixture.

We plot on a West Eurasian map the statistic _f_4(Test, Chimp; A_1, A_2), where _A_1 and _A_2 are a pair of the three ancient samples representing the three ancestral populations of Europe. a, In both Europe and the Near East/Caucasus, populations from the south have more relatedness to Stuttgart than those from the north where ANE influence is also important. b, Northern European populations share more alleles with Loschbour than with Stuttgart, as they have additional WHG ancestry beyond what was already present in EEF. c, We observe a striking contrast between Europe west of the Caucasus and the Near East in degree of relatedness to WHG. In Europe, there is a much higher degree of allele sharing with Loschbour than with MA1, which we ascribe to the 60–80% WHG/(WHG + ANE) ratio in most Europeans that we report in Supplementary Information section 14. In contrast, the Near East has no appreciable WHG ancestry but some ANE ancestry, especially in the northern Caucasus. (Jewish populations are marked with a square in this figure to assist in interpretation as their ancestry is often anomalous for their geographic regions.)

Extended Data Figure 7 Evidence for Siberian gene flow into far north-eastern Europe.

Some north-eastern European populations (Chuvash, Finnish, Russian, Mordovian, Saami) share more alleles with Han Chinese than with other Europeans who are arrayed in a cline from Stuttgart to Lithuanians/Estonians in a plot of _f_4(Test, BedouinB; Han, Mbuti) against _f_4(Test, BedouinB; MA1, Mbuti).

Extended Data Table 1 West Eurasians genotyped on the Human Origins array and key f statistics

Full size table

Extended Data Table 2 Confirmation of key findings on transversions and on whole-genome sequence data

Full size table

Extended Data Table 3 Admixture proportions for European populations

Full size table

Supplementary information

Supplementary Information

This file contains Supplementary Information Parts 1-19 – see Supplementary Contents for details.This file contains Supplementary Information Parts 1-19 – see Supplementary Contents for details. (PDF 9752 kb)

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Lazaridis, I., Patterson, N., Mittnik, A. et al. Ancient human genomes suggest three ancestral populations for present-day Europeans.Nature 513, 409–413 (2014). https://doi.org/10.1038/nature13673

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