Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans

Journal name:
Nature
Volume:
505,
Pages:
87–91
Date published:
DOI:
doi:10.1038/nature12736
Received
Accepted
Published online

The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians1, 2, 3, there is no consensus with regard to which specific Old World populations they are closest to4, 5, 6, 7, 8. Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal’ta in south-central Siberia9, to an average depth of 1×. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers10, 11, 12, and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages5. Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians2, 13. Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago14, revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native Americans derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans.

At a glance

Figures

  1. Sample locations and MA-1 genetic affinities.
    Figure 1: Sample locations and MA-1 genetic affinities.

    a, Geographical locations of Mal’ta and Afontova Gora-2 in south-central Siberia. For reference, Palaeolithic sites with individuals belonging to mtDNA haplogroup U are shown (red and black triangles): 1, Oberkassel; 2, Hohle Fels; 3, Dolni Vestonice; 4, Kostenki-14. A Palaeolithic site with an individual belonging to mtDNA haplogroup B is represented by the square: 5, Tianyuan Cave. Notable Palaeolithic sites with Venus figurines are marked by brown circles: 6, Laussel; 7, Lespugue; 8, Grimaldi; 9, Willendorf; 10, Gargarino. Other notable Palaeolithic sites are shown by grey circles: 11, Sungir; 12, Yana RHS. b, PCA (PC1 versus PC2) of MA-1 and worldwide human populations for which genomic tracts from recent European admixture in American and Siberian populations have been excluded19. c, Heat map of the statistic f3(Yoruba; MA-1, X) where X is one of 147 worldwide non-African populations (standard errors shown in Supplementary Fig. 21). The graded heat key represents the magnitude of the computed f3 statistics.

  2. Admixture graph for MA-1 and 16 complete genomes.
    Figure 2: Admixture graph for MA-1 and 16 complete genomes.

    An admixture graph with two migration edges (depicted by arrows) was fitted using TreeMix21 to relate MA-1 to 11 modern genomes from worldwide populations22, 4 modern genomes produced in this study (Avar, Mari, Indian and Tajik), and the Denisova genome22. Trees without migration, graphs with different number of migration edges, and residual matrices are shown in Supplementary Information, section 11. The drift parameter is proportional to 2Ne generations, where Ne is the effective population size. The migration weight represents the fraction of ancestry derived from the migration edge. The scale bar shows ten times the average standard error (s.e.) of the entries in the sample covariance matrix. Note that the length of the branch leading to MA-1 is affected by this ancient genome being represented by haploid genotypes.

  3. Evidence of gene flow from a population related to MA-1 and western Eurasians into Native American ancestors.
    Figure 3: Evidence of gene flow from a population related to MA-1 and western Eurasians into Native American ancestors.

    Allele frequency-based D-statistic tests20 of the forms. a, D(Yoruba, MA-1; Han, X), where X represents modern-day populations from North and South America. The D-statistic is significantly positive for all the tests, providing evidence for gene flow between Native American ancestors and the MA-1 population lineage; however, it is not informative with respect to the direction of gene flow. b, D(Yoruba, X; Han, Karitiana), where X represents non-African populations. Since all of the 17 tested western Eurasian populations are closer to Karitiana than to Han Chinese, the most parsimonious explanation is that Native Americans have western Eurasian-related ancestry. c, D(Sardinian, X; Papuan, Han), where X represents non-African populations. MA-1 is not significantly closer to Han Chinese than to Papuans, which is compatible with MA-1 having no Native American-related admixture in its ancestry. Thick and thin error bars correspond to 1 and 3 standard errors of the D-statistic, respectively.

Accession codes

Referenced accessions

Gene Expression Omnibus

Sequence Read Archive

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Author information

  1. These authors contributed equally to this work.

    • Maanasa Raghavan &
    • Pontus Skoglund

Affiliations

  1. Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5–7, 1350 Copenhagen, Denmark

    • Maanasa Raghavan,
    • Thomas W. Stafford Jr,
    • Ludovic Orlando,
    • Paula F. Campos &
    • Eske Willerslev
  2. Department of Evolutionary Biology, Uppsala University, Norbyvägen 18D, Uppsala 752 36, Sweden

    • Pontus Skoglund &
    • Mattias Jakobsson
  3. Center for the Study of the First Americans, Texas A&M University, TAMU-4352, College Station, Texas 77845-4352, USA

    • Kelly E. Graf
  4. Estonian Biocentre, Evolutionary Biology group, Tartu 51010, Estonia

    • Mait Metspalu,
    • Monika Karmin,
    • Kristiina Tambets,
    • Siiri Rootsi,
    • Sergey Litvinov,
    • Toomas Kivisild &
    • Richard Villems
  5. Department of Integrative Biology, University of California, Berkeley, California 94720, USA

    • Mait Metspalu,
    • Michael DeGiorgio &
    • Rasmus Nielsen
  6. Department of Evolutionary Biology, University of Tartu, Tartu 51010, Estonia

    • Mait Metspalu,
    • Ene Metspalu,
    • Monika Karmin &
    • Richard Villems
  7. The Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen 2200, Denmark

    • Anders Albrechtsen &
    • Ida Moltke
  8. Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA

    • Ida Moltke
  9. Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby 2800, Denmark

    • Simon Rasmussen,
    • Thomas Sicheritz-Ponten &
    • Søren Brunak
  10. AMS 14C Dating Centre, Department of Physics and Astronomy, University of Aarhus, Ny Munkegade 120, Aarhus DK-8000, Denmark

    • Thomas W. Stafford Jr
  11. Estonian Genome Center, University of Tartu, Tartu 51010, Estonia

    • Reedik Mägi
  12. Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moskvorechie Street 1, Moscow 115479, Russia

    • Elena Balanovska &
    • Oleg Balanovsky
  13. Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkina Street 3, Moscow 119991, Russia

    • Oleg Balanovsky
  14. Institute of Biochemistry and Genetics, Ufa Scientific Centre, Russian Academy of Sciences, Ufa, Bashkorostan 450054, Russia

    • Elza Khusnutdinova &
    • Sergey Litvinov
  15. Biology Department, Bashkir State University, Ufa, Bashkorostan 450074, Russia

    • Elza Khusnutdinova
  16. The Institute of Cytology and Genetics, Center for Brain Neurobiology and Neurogenetics, Siberian Branch of the Russian Academy of Sciences, Lavrentyeva Avenue, Novosibirsk 630090, Russia

    • Ludmila P. Osipova &
    • Mikhail I. Voevoda
  17. Department of Molecular Genetics, Yakut Research Center of Complex Medical Problems, Russian Academy of Medical Sciences and North-Eastern Federal University, Yakutsk, Sakha (Yakutia) 677010, Russia

    • Sardana A. Fedorova
  18. Institute of Internal Medicine, Siberian Branch of the Russian Academy of Medical Sciences, Borisa Bogatkova 175/1, Novosibirsk 630089, Russia

    • Mikhail I. Voevoda
  19. Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby 2800, Denmark

    • Thomas Sicheritz-Ponten &
    • Søren Brunak
  20. The State Hermitage Museum, 2, Dvortsovaya Ploshchad, St. Petersberg 190000, Russia

    • Svetlana Demeshchenko
  21. Department of Biological Anthropology, University of Cambridge, Cambridge CB2 1QH, UK

    • Toomas Kivisild
  22. Estonian Academy of Sciences, Tallinn 10130, Estonia

    • Richard Villems
  23. Science for Life Laboratory, Uppsala University, Norbyvägen 18D, 752 36 Uppsala, Sweden

    • Mattias Jakobsson

Contributions

E.W. and K.E.G. conceived the project. E.W. headed the project. E.W. and M.R. designed the experimental research project setup. S.D. and K.E.G. provided access to the Mal’ta and Afontova Gora-2 samples, and K.E.G. provided archaeological context for the samples. T.W.S. Jr performed AMS dating. E.B. and O.B. (Tajik individual), E.K. and S.L. (Mari and Avar individuals) provided modern DNA extracts for complete genome sequencing. E.K. and S.L. (Kazakh, Kirghiz, Uzbek and Mari individuals), L.P.O. (Selkup individuals), S.A.F. (Even, Dolgan and Yakut individuals) and M.I.V. (Altai individuals) provided access to modern DNA extracts for genotyping. R.V. carried out Illumina chip analysis on modern samples. P.F.C. performed DNA extraction from the Indian individual. M.R. performed the ancient extractions and library constructions on the modern and ancient samples —the latter with input from L.O. M.R. coordinated the sequencing. M.R. and S.Ra. performed mapping of MA-1 and AG-2 data sets with input from L.O. S.Ra., T.S.-P. and S.B. provided super-computing resources, developed the next-generation sequencing pipeline and performed mapping and genotyping for all the modern genomes. M.R. performed DNA damage analysis with input from L.O. M.M. performed the admixture analysis. M.M., E.M., K.T. and R.V. performed the mtDNA analysis. M.M., M.K., S.Ro., T.K., R.V. and R.M. performed the Y-chromosome analysis. A.A. and I.M. performed the autosomal contamination estimates, error rate estimates, D-statistics tests based on sequence reads and ngsAdmix analyses. P.S. performed biological sexing, mtDNA contamination estimates, PCA, TreeMix, MixMapper, D-statistic tests based on allele frequencies, f3-statistics and phenotypic analyses, and analysis of AG-2 using nucleotide misincorporation patterns under the supervision of R.N. and M.J. M.R., P.S. and E.W. wrote the majority of the manuscript with critical input from R.N., M.J., M.M., K.E.G., A.A., I.M. and M.D. M.M., A.A. and I.M. contributed equally to this work.

Competing financial interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to:

Sequence data for MA-1 and AG-2, produced in this study, are available for download through NCBI SRA accession number SRP029640. Data from the Illumina genotyping analysis generated in this study are available through GEO Series accession number GSE50727; PLINK files can be accessed from http://www.ebc.ee/free_data. In addition, the above data and alignments for the published modern genomes, Denisova genome, Tianyuan individual and the two ancient genomes are available at http://www.cbs.dtu.dk/suppl/malta. Raw reads and alignments for the four modern genomes sequenced in this study are available for demographic research under data access agreement with E.W.

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