Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

A mitochondrial genome sequence of a hominin from Sima de los Huesos

Abstract

Excavations of a complex of caves in the Sierra de Atapuerca in northern Spain have unearthed hominin fossils that range in age from the early Pleistocene to the Holocene1. One of these sites, the ‘Sima de los Huesos’ (‘pit of bones’), has yielded the world’s largest assemblage of Middle Pleistocene hominin fossils2,3, consisting of at least 28 individuals4 dated to over 300,000 years ago5. The skeletal remains share a number of morphological features with fossils classified as Homo heidelbergensis and also display distinct Neanderthal-derived traits6,7,8. Here we determine an almost complete mitochondrial genome sequence of a hominin from Sima de los Huesos and show that it is closely related to the lineage leading to mitochondrial genomes of Denisovans9,10, an eastern Eurasian sister group to Neanderthals. Our results pave the way for DNA research on hominins from the Middle Pleistocene.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2: Femur XIII reassembled from three parts after sampling.
Figure 3: Patterns of cytosine deamination in the libraries constructed from the Sima de los Huesos hominin femur.
Figure 4: Bayesian phylogenetic tree of hominin mitochondrial relationships based on the Sima de los Huesos mtDNA sequence determined using the inclusive filtering criteria.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

Data deposits

The Sima de los Huesos mtDNA consensus sequence (based on the inclusive filtering criteria) is deposited in GenBank under accession number KF683087.

References

  1. Carbonell, E. et al. The first hominin of Europe. Nature 452, 465–469 (2008)

    ADS  CAS  PubMed  Google Scholar 

  2. Arsuaga, J. L., Martinez, I., Gracia, A. & Lorenzo, C. The Sima de los Huesos crania (Sierra de Atapuerca, Spain). A comparative study. J. Hum. Evol. 33, 219–281 (1997)

    CAS  PubMed  Google Scholar 

  3. Arsuaga, J. L. et al. Size variation in Middle Pleistocene humans. Science 277, 1086–1088 (1997)

    CAS  PubMed  Google Scholar 

  4. Bermúdez de Castro, J. M. & Nicolas, M. E. Palaeodemography of the Atapuerca-SH Middle Pleistocene hominid sample. J. Hum. Evol. 33, 333–355 (1997)

    PubMed  Google Scholar 

  5. Bischoff, J. L. et al. Geology and preliminary dating of the hominid-bearing sedimentary fill of the Sima de los Huesos Chamber, Cueva Mayor of the Sierra de Atapuerca, Burgos, Spain. J. Hum. Evol. 33, 129–154 (1997)

    CAS  PubMed  Google Scholar 

  6. Martínez, I. & Arsuaga, J. L. The temporal bones from Sima de los Huesos Middle Pleistocene site (Sierra de Atapuerca, Spain). A phylogenetic approach. J. Hum. Evol. 33, 283–318 (1997)

    PubMed  Google Scholar 

  7. Martinón-Torres, M., Bermudez de Castro, J. M., Gomez-Robles, A., Prado-Simon, L. & Arsuaga, J. L. Morphological description and comparison of the dental remains from Atapuerca-Sima de los Huesos site (Spain). J. Hum. Evol. 62, 7–58 (2012)

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

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

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ortega, A. I. et al. Evolution of multilevel caves in the Sierra de Atapuerca (Burgos, Spain) and its relation to human occupation. Geomorphology 196, 122–137 (2013)

    ADS  Google Scholar 

  12. Arsuaga, J. L. et al. Sima de los Huesos (Sierra de Atapuerca, Spain). The site. J. Hum. Evol. 33, 109–127 (1997)

    CAS  PubMed  Google Scholar 

  13. Valdiosera, C. et al. Typing single polymorphic nucleotides in mitochondrial DNA as a way to access Middle Pleistocene DNA. Biol. Lett. 2, 601–603 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Dabney, J. 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)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  15. Willerslev, E. et al. Ancient biomolecules from deep ice cores reveal a forested southern Greenland. Science 317, 111–114 (2007)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  16. Orlando, L. et al. Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse. Nature 499, 74–78 (2013)

    ADS  CAS  PubMed  Google Scholar 

  17. Carretero, J. M. et al. Stature estimation from complete long bones in the Middle Pleistocene humans from the Sima de los Huesos, Sierra de Atapuerca (Spain). J. Hum. Evol. 62, 242–255 (2012)

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

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

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  21. Krause, J. et al. A complete mtDNA genome of an early modern human from Kostenki, Russia. Curr. Biol. 20, 231–236 (2010)

    CAS  PubMed  Google Scholar 

  22. Sawyer, S., Krause, J., Guschanski, K., Savolainen, V. & Paabo, S. Temporal patterns of nucleotide misincorporations and DNA fragmentation in ancient DNA. PLoS ONE 7, e34131 (2012)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

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

    ADS  CAS  PubMed  Google Scholar 

  24. Ronquist, F. & Huelsenbeck, J. P. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19, 1572–1574 (2003)

    CAS  PubMed  Google Scholar 

  25. Shapiro, B. et al. A Bayesian phylogenetic method to estimate unknown sequence ages. Mol. Biol. Evol. 28, 879–887 (2011)

    CAS  PubMed  Google Scholar 

  26. Arsuaga, J. L., Martinez, I., Gracia, A., Carretero, J. M. & Carbonell, E. Three new human skulls from the Sima de los Huesos Middle Pleistocene site in Sierra de Atapuerca, Spain. Nature 362, 534–537 (1993)

    ADS  CAS  PubMed  Google Scholar 

  27. Arsuaga, J. L. Colloquium paper: terrestrial apes and phylogenetic trees. Proc. Natl Acad. Sci. USA 107 (Suppl. 2). 8910–8917 (2010)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hublin, J. J. Out of Africa: Modern human origins special feature: The origin of Neandertals. Proc. Natl Acad. Sci. USA 106, 16022–16027 (2009)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mounier, A., Marchal, F. & Condemi, S. Is Homo heidelbergensis a distinct species? New insight on the Mauer mandible. J. Hum. Evol. 56, 219–246 (2009)

    PubMed  Google Scholar 

  30. Carbonell, E. et al. An Early Pleistocene hominin mandible from Atapuerca-TD6, Spain. Proc. Natl Acad. Sci. USA 102, 5674–5678 (2005)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  31. Dabney, J. & Meyer, M. 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)

    CAS  PubMed  Google Scholar 

  32. Kircher, M., Sawyer, S. & Meyer, M. Double indexing overcomes inaccuracies in multiplex sequencing on the Illumina platform. Nucleic Acids Res. 40, e3 (2012)

    CAS  PubMed  Google Scholar 

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

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rohland, N. & Reich, D. Cost-effective, high-throughput DNA sequencing libraries for multiplexed target capture. Genome Res. 22, 939–946 (2012)

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Maricic, T., Whitten, M. & Paabo, S. Multiplexed DNA sequence capture of mitochondrial genomes using PCR products. PLoS ONE 5, e14004 (2010)

    ADS  PubMed  PubMed Central  Google Scholar 

  36. Renaud, G., Kircher, M., Stenzel, U. & Kelso, J. freeIbis: an efficient basecaller with calibrated quality scores for Illumina sequencers. Bioinformatics 29, 1208–1209 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Kircher, M. Analysis of high-throughput ancient DNA sequencing data. Methods Mol. Biol. 840, 197–228 (2012)

    CAS  PubMed  Google Scholar 

  38. Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009)

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ingman, M., Kaessmann, H., Paabo, S. & Gyllensten, U. Mitochondrial genome variation and the origin of modern humans. Nature 408, 708–713 (2000)

    ADS  CAS  PubMed  Google Scholar 

  40. Fu, Q. et al. A revised timescale for human evolution based on ancient mitochondrial genomes. Curr. Biol. 23, 553–559 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

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

    ADS  CAS  PubMed  Google Scholar 

  42. Zsurka, G. et al. Distinct patterns of mitochondrial genome diversity in bonobos (Pan paniscus) and humans. BMC Evol. Biol. 10, 270 (2010)

    PubMed  PubMed Central  Google Scholar 

  43. Bjork, A., Liu, W., Wertheim, J. O., Hahn, B. H. & Worobey, M. Evolutionary history of chimpanzees inferred from complete mitochondrial genomes. Mol. Biol. Evol. 28, 615–623 (2011)

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Posada, D. & Crandall, K. A. MODELTEST: testing the model of DNA substitution. Bioinformatics 14, 817–818 (1998)

    Article  CAS  PubMed  Google Scholar 

  46. Drummond, A. J. & Rambaut, A. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol. Biol. 7, 214 (2007)

    PubMed  PubMed Central  Google Scholar 

  47. Kass, R. E. & Raftery, A. E. Bayes Factors. J. Am. Stat. Assoc. 90, 773–795 (1995)

    MathSciNet  MATH  Google Scholar 

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

    ADS  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Stone, A. C. et al. More reliable estimates of divergence times in Pan using complete mtDNA sequences and accounting for population structure. Phil. Trans. R. Soc. Lond. B 365, 3277–3288 (2010)

    CAS  Google Scholar 

  51. Soares, P. et al. Correcting for purifying selection: an improved human mitochondrial molecular clock. Am. J. Hum. Genet. 84, 740–759 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank J. Dabney, M. Dannemann, C. de Filippo, S. Lippold, K. Prüfer, M. Slatkin, M. Stiller, C. Valdiosera and B. Viola for discussions and comments on the manuscript; G. Renaud and U. Stenzel for help with sequence data processing; B. Höber and A. Weihmann for performing the sequencing runs; M. Gansauge, P. Korlević, R. Rodríguez and I. Ureña for help in the laboratory; M. Schreiber for help with graphics; J. Trueba for providing the fossil image; M. Cruz Ortega for restoration of the fossil and the rest of the members of the Sima de los Huesos excavation team for decades of continuous efforts. Genetics work was funded by the Max Planck Society and its Presidential Innovation Fund. Field work at the Sierra de Atapuerca sites is funded by the Junta de Castilla y León and the Fundación Atapuerca. Research was supported by Spanish Ministerio de Ciencia e Innovación (project CGL2009-12703-C03) and Spanish Ministerio de Economía y Competitividad (project CGL2012-38434-C03).

Author information

Authors and Affiliations

Authors

Contributions

M.M. designed the experiments and analysed the data; Q.F. performed phylogenetic analyses; A.A., I.G. and B.N. performed the experiments; J.-L.A., I.M., A.G., J.M.B. and E.C. excavated the fossil and provided expert archaeological and anthropological information; J.-L.A. and S.P. were involved in study design; and M.M., J.-L.A. and S.P. wrote the manuscript.

Corresponding author

Correspondence to Matthias Meyer.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Size distribution of all overlap-merged sequences generated by shotgun sequencing (before mapping).

Extended Data Figure 2 5′ and 3′ C to T substitution frequencies plotted against the number of unique mitochondrial sequences retrieved from each sample library.

Libraries prepared from re-extracted pellets or surface material are highlighted in colour.

Extended Data Figure 3 Sequence length distribution of unique sequences.

The distribution obtained from the Sima de los Huesos cave bear is shown for comparison.

Extended Data Figure 4 Sequence coverage of the mitochondrial genome obtained from sequences with terminal C to T substitutions.

Extended Data Figure 5 Sequence coverage of the mitochondrial genome plotted separately for both capture probe sets used (based on sequences with a C to T substitution at the first or last alignment position).

Extended Data Figure 6 Complete view of the mid-point rooted phylogenetic tree constructed with a Bayesian approach under a GTR + I + Γ model of sequence evolution using the Sima de los Huesos consensus sequence generated with inclusive filters as well as 54 present-day humans, 9 ancient humans, 7 Neanderthals, 2 Denosivans, 22 bonobos and 24 chimpanzees.

The posterior probabilities are provided for the major nodes.

Extended Data Table 1 Characteristics of all libraries prepared for this study
Extended Data Table 2 Results from shallow shotgun sequencing of a subset of libraries
Extended Data Table 3 Number of sequences retained in the sample libraries after each step of processing and filtering
Extended Data Table 4 Inferred time to the most recent common ancestor (TMRCA) of the modern human, Neanderthal, chimpanzee and bonobo mtDNAs, as well as divergence estimates for human/chimpanzee and bonobo/chimpanzee mtDNA (continuation of Table 1)

Related audio

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meyer, M., Fu, Q., Aximu-Petri, A. et al. A mitochondrial genome sequence of a hominin from Sima de los Huesos. Nature 505, 403–406 (2014). https://doi.org/10.1038/nature12788

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature12788

This article is cited by

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.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing