Article

Ancient gene flow from early modern humans into Eastern Neanderthals

  • Nature volume 530, pages 429433 (25 February 2016)
  • doi:10.1038/nature16544
  • Download Citation
Received:
Accepted:
Published:

Abstract

It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000–65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.

  • Subscribe to Nature for full access:

    $199

    Subscribe

Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.

Accessions

Primary accessions

European Nucleotide Archive

Data deposits

Sequence data are available in the European Nucleotide Archive (ENA) under accession number PRJEB11828.

References

  1. 1.

    et al. Neandertal roots: Cranial and chronological evidence from Sima de los Huesos. Science 344, 1358–1363 (2014)

  2. 2.

    et al. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505, 43–49 (2014)

  3. 3.

    et al. A draft sequence of the Neandertal genome. Science 328, 710–722 (2010)

  4. 4.

    et al. Genome sequence of a 45,000-year-old modern human from western Siberia. Nature 514, 445–449 (2014)

  5. 5.

    et al. An early modern human from Romania with a recent Neanderthal ancestor. Nature (2015)

  6. 6.

    et al. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, 1053–1060 (2010)

  7. 7.

    et al. A high-coverage genome sequence from an archaic Denisovan individual. Science 338, 222–226 (2012)

  8. 8.

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

  9. 9.

    et al. Ancient west Eurasian ancestry in southern and eastern Africa. Proc. Natl Acad. Sci. USA 111, 2632–2637 (2014)

  10. 10.

    et al. Ancient Ethiopian genome reveals extensive Eurasian admixture throughout the African continent. Science 350, 820–822 (2015)

  11. 11.

    , , , & Bayesian inference of ancient human demography from individual genome sequences. Nature Genet. 43, 1031–1034 (2011)

  12. 12.

    , , , & The date of interbreeding between Neandertals and modern humans. PLoS Genet. 8, e1002947 (2012)

  13. 13.

    , , & Genome-wide inference of ancestral recombination graphs. PLoS Genet. 10, e1004342 (2014)

  14. 14.

    et al. Targeted investigation of the Neandertal genome by array-based sequence capture. Science 328, 723–725 (2010)

  15. 15.

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

  16. 16.

    , , & The nuclear receptor fetoprotein transcription factor is coexpressed with its target gene HNF-3β in the developing murine liver intestine and pancreas. Mech. Dev. 89, 185–188 (1999)

  17. 17.

    FOXP2 and the role of cortico-basal ganglia circuits in speech and language evolution. Curr. Opin. Neurobiol. 21, 415–424 (2011)

  18. 18.

    , , & Widespread genomic signatures of natural selection in hominid evolution. PLoS Genet. 5, e1000471 (2009)

  19. 19.

    , , , & Evidence for increased levels of positive and negative selection on the X chromosome versus autosomes in humans. Mol. Biol. Evol. 31, 2267–2282 (2014)

  20. 20.

    et al. The genomic landscape of Neanderthal ancestry in present-day humans. Nature 507, 354–357 (2014)

  21. 21.

    et al. Genomic patterns of homozygosity in worldwide human populations. Am. J. Hum. Genet. 91, 275–292 (2012)

  22. 22.

    et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034–1050 (2005)

  23. 23.

    et al. Patterns of coding variation in the complete exomes of three Neandertals. Proc. Natl Acad. Sciences USA 111, 6666–6671 (2014)

  24. 24.

    in Neandertals and Modern Humans in Western Asia (eds , & ) (Kluwer Academic Publishers, 1998)

  25. 25.

    , , , & Thermoluminescence date for the Mousterian burial site of Es-Skhul, Mt. Carmel. J. Archaeol. Sci. 20, 169–174 (1993)

  26. 26.

    et al. U-series and ESR analyses of bones and teeth relating to the human burials from Skhul. J. Hum. Evol. 49, 316–334 (2005)

  27. 27.

    et al. The southern route “Out of Africa”: evidence for an early expansion of modern humans into Arabia. Science 331, 453–456 (2011)

  28. 28.

    & “Out of Arabia” and the Middle–Upper Palaeolithic transition in the southern Levant. Quartär 61, 49–85 (2014)

  29. 29.

    et al. The earliest unequivocally modern humans in southern China. Nature 526, 696–699 (2015)

  30. 30.

    & Comparison and optimization of ancient DNA extraction. Biotechniques 42, 343–352 (2007)

  31. 31.

    & Illumina sequencing library preparation for highly multiplexed target capture and sequencing. Cold Spring Harb. Protocols 2010 , (2010)

  32. 32.

    , & Double indexing overcomes inaccuracies in multiplex sequencing on the Illumina platform. Nucleic Acids Res. 40, e3 (2012)

  33. 33.

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

  34. 34.

    et al. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nature Biotechnol. 27, 182–189 (2009)

  35. 35.

    et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010)

  36. 36.

    , , , & Enredo and Pecan: genome-wide mammalian consistency-based multiple alignment with paralogs. Genome Res. 18, 1814–1828 (2008)

  37. 37.

    Generating samples under a Wright–Fisher neutral model of genetic variation. Bioinformatics 18, 337–338 (2002)

  38. 38.

    et al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328, 636–639 (2010)

  39. 39.

    Cross-cultural estimation of the human generation interval for use in genetics-based population divergence studies. Am. J. Phys. Anthropol. 128, 415–423 (2005)

  40. 40.

    et al. Genome sequencing highlights the dynamic early history of dogs. PLoS Genet. 10, e1004016 (2014)

  41. 41.

    et al. Demographic history and rare allele sharing among human populations. Proc. Natl Acad. Sci. USA 108, 11983–11988 (2011)

  42. 42.

    et al. Great ape genetic diversity and population history. Nature 499, 471–475 (2013)

  43. 43.

    et al. BioMart and Bioconductor: a powerful link between biological databases and microarray data analysis. Bioinformatics 21, 3439–3440 (2005)

  44. 44.

    et al. Genome-wide inference of natural selection on human transcription factor binding sites. Nature Genet. 45, 723–729 (2013)

Download references

Acknowledgements

We thank M. Slatkin, F. Racimo, J. Kelso, K. Prüfer, M. Stoneking and D. Reich for comments; the MPI-EVA sequencing group, B. Nickel and R. Schultz for technical support; A. Heinze, S. Sawyer and J. Dabney for sequencing library preparation; U. Stenzel and G. Renaud for help with sequence processing. M.J.H. was supported by the National Science Foundation Graduate Research Fellowship under grant DGE-1144153. Q.F. was funded in part by the Special Foundation of the President of the Chinese Academy of Sciences. T.M-B. was supported by ICREA, EMBO YIP 2013 and Fundació Barcelona Zoo. The Max Planck Society, the Krekeler Foundation, MINECO (grants BFU2014-55090-P FEDER, BFU2015-7116-ERC and BFU2015-6215-ERC to T.M-B. and BFU2012-34157 FEDER to C.L.-F.) and the US National Institutes of Health (grant GM102192 to A.S. and U01 MH106874 to T.M-B.) provided financial support.

Author information

Author notes

    • Martin Kuhlwilm
    •  & Ilan Gronau

    These authors contributed equally to this work.

Affiliations

  1. Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany

    • Martin Kuhlwilm
    • , Cesare de Filippo
    • , Martin Kircher
    • , Qiaomei Fu
    • , Hernán A. Burbano
    • , Aida M. Andrés
    • , Svante Pääbo
    • , Matthias Meyer
    •  & Sergi Castellano
  2. Efi Arazi School of Computer Science, Herzliya Interdisciplinary Center (IDC), Herzliya 46150, Israel

    • Ilan Gronau
  3. Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14850, USA

    • Melissa J. Hubisz
    •  & Adam Siepel
  4. Institute of Evolutionary Biology (UPF-CSIC), 08003 Barcelona, Spain

    • Javier Prado-Martinez
    • , Carles Lalueza-Fox
    •  & Tomas Marques-Bonet
  5. Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA

    • Martin Kircher
  6. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Qiaomei Fu
  7. Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, IVPP, CAS, Beijing 100044, China

    • Qiaomei Fu
  8. Department of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany

    • Hernán A. Burbano
  9. Área de Prehistoria, Departamento de Historia, Universidad de Oviedo, 33011 Oviedo, Spain

    • Marco de la Rasilla
  10. Departamento de Paleobiología, Museo Nacional de Ciencias Naturales, CSIC, 28006 Madrid, Spain

    • Antonio Rosas
  11. Anthropology Center of the Croatian Academy of Sciences and Arts, 10000 Zagreb, Croatia

    • Pavao Rudan
    • , Željko Kucan
    •  & Ivan Gušic
  12. Croatian Academy of Sciences and Arts, Institute for Quaternary Paleontology and Geology, 10000 Zagreb, Croatia

    • Dejana Brajkovic
  13. Catalan Institution of Research and Advanced Studies (ICREA), 08010 Barcelona, Spain

    • Tomas Marques-Bonet
  14. Centro Nacional de Análisis Genómico (CRG-CNAG), 08028 Barcelona, Spain

    • Tomas Marques-Bonet
  15. Department of Anthropology, University of Toronto, Toronto, Ontario M5S 2S2, Canada

    • Bence Viola
  16. Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany

    • Bence Viola
  17. Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

    • Adam Siepel

Authors

  1. Search for Martin Kuhlwilm in:

  2. Search for Ilan Gronau in:

  3. Search for Melissa J. Hubisz in:

  4. Search for Cesare de Filippo in:

  5. Search for Javier Prado-Martinez in:

  6. Search for Martin Kircher in:

  7. Search for Qiaomei Fu in:

  8. Search for Hernán A. Burbano in:

  9. Search for Carles Lalueza-Fox in:

  10. Search for Marco de la Rasilla in:

  11. Search for Antonio Rosas in:

  12. Search for Pavao Rudan in:

  13. Search for Dejana Brajkovic in:

  14. Search for Željko Kucan in:

  15. Search for Ivan Gušic in:

  16. Search for Tomas Marques-Bonet in:

  17. Search for Aida M. Andrés in:

  18. Search for Bence Viola in:

  19. Search for Svante Pääbo in:

  20. Search for Matthias Meyer in:

  21. Search for Adam Siepel in:

  22. Search for Sergi Castellano in:

Contributions

M.M. and Q.F. performed experiments; M.Ku., I.Gr., M.J.H., C.d.F., J.P.-M., M.Ki, Q.F., H.A.B., T.M.-B., A.M.A., S.P., M.M., A.S. and S.C. analysed genetic data; C.L.-F., M.d.l.R., A.R., P.R., D.B., Ž.,K., I.Gu. and B.V. analysed anthropological data; M.Ku., I.Gr., M.J.H., B.V., S.P., A.S. and S.C. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Adam Siepel or Sergi Castellano.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Text 1-11, Supplementary Tables 1-19, Supplementary Figures 1-34 and additional references (see Contents).

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.