Abstract

A unique assemblage of 28 hominin individuals, found in Sima de los Huesos in the Sierra de Atapuerca in Spain, has recently been dated to approximately 430,000 years ago1. An interesting question is how these Middle Pleistocene hominins were related to those who lived in the Late Pleistocene epoch, in particular to Neanderthals in western Eurasia and to Denisovans, a sister group of Neanderthals so far known only from southern Siberia. While the Sima de los Huesos hominins share some derived morphological features with Neanderthals, the mitochondrial genome retrieved from one individual from Sima de los Huesos is more closely related to the mitochondrial DNA of Denisovans than to that of Neanderthals2. However, since the mitochondrial DNA does not reveal the full picture of relationships among populations, we have investigated DNA preservation in several individuals found at Sima de los Huesos. Here we recover nuclear DNA sequences from two specimens, which show that the Sima de los Huesos hominins were related to Neanderthals rather than to Denisovans, indicating that the population divergence between Neanderthals and Denisovans predates 430,000 years ago. A mitochondrial DNA recovered from one of the specimens shares the previously described relationship to Denisovan mitochondrial DNAs, suggesting, among other possibilities, that the mitochondrial DNA gene pool of Neanderthals turned over later in their history.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Accessions

Primary accessions

European Nucleotide Archive

Data deposits

Sequences generated in this study have been deposited in the European Nucleotide Archive under study accession number PRJEB10597.

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. A mitochondrial genome sequence of a hominin from Sima de los Huesos. Nature 505, 403–406 (2014)

  3. 3.

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

  4. 4.

    et al. Nuclear and mitochondrial DNA sequences from two Denisovan individuals. Proc. Natl Acad. Sci. USA 112, 15696–15700 (2015)

  5. 5.

    & Denisovan ancestry in East Eurasian and Native American populations. Mol. Biol. Evol. 32, 2665–2674 (2015)

  6. 6.

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

  7. 7.

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

  8. 8.

    et al. Postcranial morphology of the middle Pleistocene humans from Sima de los Huesos, Spain. Proc. Natl Acad. Sci. USA 112, 11524–11529 (2015)

  9. 9.

    et al. Patterns of damage in genomic DNA sequences from a Neandertal. Proc. Natl Acad. Sci. USA 104, 14616–14621 (2007)

  10. 10.

    et al. The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature 464, 894–897 (2010)

  11. 11.

    , , , & Temporal patterns of nucleotide misincorporations and DNA fragmentation in ancient DNA. PLoS ONE 7, e34131 (2012)

  12. 12.

    et al. Complete mitochondrial genome sequence of a Middle Pleistocene cave bear reconstructed from ultrashort DNA fragments. Proc. Natl Acad. Sci. USA 110, 15758–15763 (2013)

  13. 13.

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

  14. 14.

    et al. An Aboriginal Australian genome reveals separate human dispersals into Asia. Science 334, 94–98 (2011)

  15. 15.

    The status of Homo heidelbergensis (Schoetensack 1908). Evol. Anthropol. 21, 101–107 (2012)

  16. 16.

    Understanding ancient hominin dispersals using artefactual data: a phylogeographic analysis of Acheulean handaxes. PLoS ONE 4, e7404 (2009)

  17. 17.

    & Towards a theory of modern human origins: Geography, demography, and diversity in recent human evolution. Yb. Phys. Anthropol . 41, 137–176 (1998)

  18. 18.

    Hominin variability, climatic instability and population demography in Middle Pleistocene Europe. Quat. Sci. Rev. 30, 1511–1524 (2011)

  19. 19.

    et al. New radiometric ages for the BH-1 hominin from Balanica (Serbia): implications for understanding the role of the Balkans in Middle Pleistocene human evolution. PLoS ONE 8, e54608 (2013)

  20. 20.

    et al. Reducing microbial and human contamination in DNA extractions from ancient bones and teeth. Biotechniques 59, 87–93 (2015)

  21. 21.

    & Single-stranded DNA library preparation for the sequencing of ancient or damaged DNA. Nature Protocols 8, 737–748 (2013)

  22. 22.

    , , , , & Mammalian mitochondrial capture, a tool for rapid screening of DNA preservation in faunal and undiagnostic remains, and its application to Middle Pleistocene specimens from Qesem Cave (Israel). Quat. Int. (2015)

  23. 23.

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

  24. 24.

    & Length and GC-biases during sequencing library amplification: a comparison of various polymerase-buffer systems with ancient and modern DNA sequencing libraries. Biotechniques 52, 87–94 (2012)

  25. 25.

    , & Multiplexed DNA sequence capture of mitochondrial genomes using PCR products. PLoS ONE 5, e14004 (2010)

  26. 26.

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

  27. 27.

    , , & freeIbis: an efficient basecaller with calibrated quality scores for Illumina sequencers. Bioinformatics 29, 1208–1209 (2013)

  28. 28.

    , & leeHom: adaptor trimming and merging for Illumina sequencing reads. Nucleic Acids Res. 42, e141 (2014)

  29. 29.

    & Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760 (2009)

  30. 30.

    et al. A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing. Cell 134, 416–426 (2008)

  31. 31.

    et al. Targeted retrieval and analysis of five Neandertal mtDNA genomes. Science 325, 318–321 (2009)

  32. 32.

    & Selective enrichment of damaged DNA molecules for ancient genome sequencing. Genome Res. 24, 1543–1549 (2014)

  33. 33.

    et al. Separating endogenous ancient DNA from modern day contamination in a Siberian Neandertal. Proc. Natl Acad. Sci. USA 111, 2229–2234 (2014)

  34. 34.

    et al. Man’s place in Hominoidea revealed by mitochondrial DNA genealogy. J. Mol. Evol. 35, 32–43 (1992)

  35. 35.

    & MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30, 772–780 (2013)

  36. 36.

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

Download references

Acknowledgements

We thank B. Höber and A. Weihmann for help with sequencing the libraries, G. Renaud for processing the raw sequence data, S. Castellano and U. Stenzel for discussions and comments on the manuscript. Genetics work was funded by the Max Planck Society and its Presidential Innovation Fund. Field work at the Sierra de Atapuerca sites was funded by the Junta de Castilla y Leon, the Fundacion Atapuerca, the Spanish Ministerio de Ciencia e Innovacion (project CGL2009-12703-C03) and the Spanish Ministerio de Economia y Competitividad (project CGL2012-38434-C03).

Author information

Affiliations

  1. Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany

    • Matthias Meyer
    • , Cesare de Filippo
    • , Sarah Nagel
    • , Ayinuer Aximu-Petri
    • , Birgit Nickel
    • , Janet Kelso
    • , Kay Prüfer
    •  & Svante Pääbo
  2. Centro de Investigación Sobre la Evolución y Comportamiento Humanos, Universidad Complutense de Madrid–Instituto de Salud Carlos III, 28029 Madrid, Spain

    • Juan-Luis Arsuaga
    • , Ignacio Martínez
    •  & Ana Gracia
  3. Departamento de Paleontología, Facultad de Ciencias Geológicas, Universidad Complutense de Madrid, 28040 Madrid, Spain

    • Juan-Luis Arsuaga
  4. Área de Paleontología, Departamento de Geografía y Geología, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain

    • Ignacio Martínez
    •  & Ana Gracia
  5. Centro Nacional de Investigación sobre la Evolución Humana, Paseo Sierra de Atapuerca, 09002 Burgos, Spain

    • José María Bermúdez de Castro
  6. Department of Anthropology, University College London, 14 Taviton Street, London WC1H 0BW, UK

  7. Institut Català de Paleoecologia Humana i Evolució Social, C/Marcel·lí Domingo s/n (Edifici W3), Campus Sescelades, 43007 Tarragona, Spain

    • Eudald Carbonell
  8. Àrea de Prehistòria, Departament d’Història i Història de l’Art, Universitat Rovira i Virgili, Facultat de Lletres, Avinguda de Catalunya, 35, 43002 Tarragona, Spain

    • Eudald Carbonell
  9. Department of Anthropology, University of Toronto, 19 Russell Street, Toronto, Ontario M5S 2S2, Canada

    • Bence Viola

Authors

  1. Search for Matthias Meyer in:

  2. Search for Juan-Luis Arsuaga in:

  3. Search for Cesare de Filippo in:

  4. Search for Sarah Nagel in:

  5. Search for Ayinuer Aximu-Petri in:

  6. Search for Birgit Nickel in:

  7. Search for Ignacio Martínez in:

  8. Search for Ana Gracia in:

  9. Search for José María Bermúdez de Castro in:

  10. Search for Eudald Carbonell in:

  11. Search for Bence Viola in:

  12. Search for Janet Kelso in:

  13. Search for Kay Prüfer in:

  14. Search for Svante Pääbo in:

Contributions

M.M., J.-L.A. and S.P. directed the experimental work and wrote the manuscript. M.M. designed the laboratory experiments, which S.N., A.A. and B.N. performed. M.M., C.d.F., B.V., J.K. and K.P. analysed the data. J.-L.A., I.M., A.G., J.M.B. and E.C. excavated the fossil and provided archaeological expertise.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Matthias Meyer.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Text, Supplementary Figures 1-2, Supplementary Tables 1-4 and additional references.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nature17405

Further reading

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.