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The complete genome sequence of a Neanderthal from the Altai Mountains

Naturevolume 505, pages43–49 (2014)Cite this article

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Abstract

We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.

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Figure 1: Toe phalanx and location of Neanderthal samples for which genome-wide data are available.
Figure 2: Phylogenetic relationships of the Altai Neanderthal.
Figure 3: Indications of inbreeding in the Altai Neanderthal individual.
Figure 4: Inference of population size change over time.
Figure 5: Relatedness of introgressing archaic and sequenced archaic samples.
Figure 6: Neanderthal gene flow into Siberian Denisovans.
Figure 7: Altai and Denisovan allele sharing with Africans stratified by African allele frequency.
Figure 8: A possible model of gene flow events in the Late Pleistocene.

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Accession codes

Accessions

European Nucleotide Archive

Data deposits

All sequence data have been submitted to the European Nucleotide Archive (ENA) and are available under the following accessions: Altai Neanderthal:ERP002097, Mezmaiskaya Neanderthal:ERP002447. The data from the 25 present-day human genomes and 13 experimentally phased present-day genomes are available as a public dataset fromhttp://aws.amazon.com/datasets/ and fromhttp://cdna.eva.mpg.de/neandertal/altai/.

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Acknowledgements

We thank M. Hammer, C. Winkler and W. Klitz for sharing DNA samples; W. Huttner and his group, B. Peter, J. G. Schraiber and M. A. Yang for helpful discussions; and A. Lewis and R. Qiu for technical assistance. N.P. and D.R. are grateful for the chance to discuss these results with Peter Waddell who independently found evidence of a deeply diverged hominin admixing into the Denisova genome. D.R. and E.E.E. are Howard Hughes Medical Institute Investigators. D.R. and N.P. were supported by NSF grant number 1032255 and NIH grant GM100233; E.E.E. by NIH grant HG002385; J.S. by grant HG006283 from the National Genome Research Institute (NHGRI); S.S. by a post-doctoral fellowship from the Harvard University Science of the Human Past Program; F.J. and M.S. in part by a grant from the NIH (R01-GM40282); P.H.S. by an HHMI International Student Fellowship. We thank the team at the NIH Intramural Sequencing Center and Alice Young in particular, for generating some of the sequence reported here. This research was supported in part by the Paul G. Allen Family Foundation. Major funding support came from the Presidential Innovation Fund of the Max Planck Society.

Author information

Author notes

  1. Ines Hellmann

    Present address: Present address: Ludwig-Maximilians-Universität München, Martinsried, 82152 Munich, Germany.,

Authors and Affiliations

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

    Kay Prüfer, Susanna Sawyer, Anja Heinze, Gabriel Renaud, Cesare de Filippo, Michael Dannemann, Qiaomei Fu, Martin Kircher, Martin Kuhlwilm, Michael Lachmann, Matthias Meyer, Matthias Ongyerth, Michael Siebauer, Christoph Theunert, Janet Kelso & Svante Pääbo

  2. Department of Integrative Biology, University of California, Berkeley, 94720-3140, California, USA

    Fernando Racimo, Flora Jay & Montgomery Slatkin

  3. Broad Institute of MIT and Harvard, Cambridge, 02142, Massachusetts, USA

    Nick Patterson, Sriram Sankararaman, Heng Li, Swapan Mallick, Arti Tandon & David Reich

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

    Sriram Sankararaman, Swapan Mallick, Arti Tandon, Priya Moorjani, Joseph Pickrell & David Reich

  5. Department of Genome Sciences, University of Washington, Seattle, 98195, Washington, USA

    Peter H. Sudmant, Martin Kircher, Jacob O. Kitzman, Jay Shendure & Evan E. Eichler

  6. Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing, 100044, China

    Qiaomei Fu

  7. Genome Technology Branch and NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    James C. Mullikin

  8. Department of Biomolecular Engineering, University of California, Santa Cruz, 95064, California, USA

    Samuel H. Vohr & Richard E. Green

  9. Max F. Perutz Laboratories, Mathematics and Bioscience Group, Campus Vienna Biocenter 5, Vienna 1030, Austria ,

    Ines Hellmann

  10. Department of Biology, Emory University, Atlanta, 30322, Georgia, USA

    Philip L. F. Johnson

  11. Fondation Jean Dausset, Centre d'Étude du Polymorphisme Humain (CEPH), 75010 Paris, France ,

    Hélène Blanche & Howard Cann

  12. Howard Hughes Medical Institute, Seattle, 98195, Washington, USA

    Evan E. Eichler

  13. Allen Institute for Brain Science, Seattle, 98103, Washington, USA

    Ed S. Lein & Trygve E. Bakken

  14. ANO Laboratory of Prehistory 14 Linia 3-11, St. Petersburg 1990 34, Russia ,

    Liubov V. Golovanova & Vladimir B. Doronichev

  15. Palaeolithic Department, Institute of Archaeology and Ethnography, Russian Academy of Sciences, Siberian Branch, 630090 Novosibirsk, Russia,

    Michael V. Shunkov & Anatoli P. Derevianko

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

    Bence Viola

  17. Howard Hughes Medical Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA

    David Reich

Authors
  1. Kay Prüfer
  2. Fernando Racimo
  3. Nick Patterson
  4. Flora Jay
  5. Sriram Sankararaman
  6. Susanna Sawyer
  7. Anja Heinze
  8. Gabriel Renaud
  9. Peter H. Sudmant
  10. Cesare de Filippo
  11. Heng Li
  12. Swapan Mallick
  13. Michael Dannemann
  14. Qiaomei Fu
  15. Martin Kircher
  16. Martin Kuhlwilm
  17. Michael Lachmann
  18. Matthias Meyer
  19. Matthias Ongyerth
  20. Michael Siebauer
  21. Christoph Theunert
  22. Arti Tandon
  23. Priya Moorjani
  24. Joseph Pickrell
  25. James C. Mullikin
  26. Samuel H. Vohr
  27. Richard E. Green
  28. Ines Hellmann
  29. Philip L. F. Johnson
  30. Hélène Blanche
  31. Howard Cann
  32. Jacob O. Kitzman
  33. Jay Shendure
  34. Evan E. Eichler
  35. Ed S. Lein
  36. Trygve E. Bakken
  37. Liubov V. Golovanova
  38. Vladimir B. Doronichev
  39. Michael V. Shunkov
  40. Anatoli P. Derevianko
  41. Bence Viola
  42. Montgomery Slatkin
  43. David Reich
  44. Janet Kelso
  45. Svante Pääbo

Contributions

S.Saw., A.H. and Q.F. performed the experiments; K.P., F.R., N.P., F.J., S.San., S.Saw., A.H., G.R., P.H.S., C.d.F., M.D., Q.F., M.Ki., M.Ku., M.L., M.M., M.O., M.Si., C.T., H.L., S.M., A.T., P.M., J.P., J.C.M., S.H.V., R.E.G., I.H., P.L.F.J., J.O.K., J.S., E.E.E., E.S.L., T.E.B., M.Sl., D.R., J.K., and S.P. analysed genetic data; L.V.G., V.B.D., M.V.S., A.P.D. and B.V. analysed archaeological and anthropological data; H.B. and H.C. provided samples and reagents; K.P., J.K. and S.P. wrote and edited the manuscript with input from all authors.

Corresponding authors

Correspondence toMontgomery Slatkin,David Reich orSvante Pääbo.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Heterozygosity estimates for the Altai Neanderthal individual, the Denisovan individual, non-Africans and Africans.

The bars for the latter two give the range of heterozygosity observed among 15 non-African and 10 African individuals, respectively (Supplementary Information section 9).

Extended Data Figure 2 Neanderthal-introgressed loci in Denisova.

Divergence of the Altai Neanderthal to the most closely related Denisovan haplotype in windows of at least 200 kb on chromosome 6. Divergence is given as percentage of human–chimpanzee divergence and bars represent ± 1 standard error.

Extended Data Table 1 Neanderthal ancestry estimate
Extended Data Table 2 SelectedD-statistics supporting inferences about gene flows
Extended Data Table 3 Lineage-specific segmental duplications along each of the terminal branches and genes encompassed

Supplementary information

Supplementary Information

This file contains Supplementary Text, Tables and Figures – see contents page for details. (PDF 16537 kb)

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Prüfer, K., Racimo, F., Patterson, N.et al. The complete genome sequence of a Neanderthal from the Altai Mountains.Nature505, 43–49 (2014). https://doi.org/10.1038/nature12886

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Comments

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  1. Axel Berger

    I wonder how many secondary sources will remark on the last sentence "further work is necessary to establish if and how this gene flow event occurred" and not just quote the result as established fact. In the case of the first Neanderthal genome, Green 2010, it was not a single one that I'm aware of.

  2. JM VReplied toAxel Berger

    Such a paper is not the end of the line. There will be further work corroborating or disputing it. All this paper does is show that there is some level of evidence for it.

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Editorial Summary

Genome sequence of Neanderthal woman

Recent excavations in the Denisova Cave in the Altai Mountains of southern Siberia have yielded a wealth of hominin fossils from a site that has been occupied for perhaps 250,000 years or more. Now a high-quality genome sequence has been determined from a circa 50,000-year-old toe bone — a proximal toe phalanx — excavated from the east gallery of Denisova Cave in 2010. The sequence is that of a Neanderthal woman whose parents were closely related — perhaps half-siblings or uncle and niece. Such inbreeding was also common among her recent ancestors. Comparisons with other archaic and present-day human genomes reveal several gene-flow events among Neanderthals, the closely related Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. The high-quality Neanderthal genome also helps to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.

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