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.

An African origin for the intimate association between humans and Helicobacter pylori

Nature volume 445, pages 915–918 (2007)Cite this article

Abstract

Infection of the stomach by Helicobacter pylori is ubiquitous among humans. However, although H. pylori strains from different geographic areas are associated with clear phylogeographic differentiation1,2,3,4, the age of an association between these bacteria with humans remains highly controversial5,6. Here we show, using sequences from a large data set of bacterial strains that, as in humans, genetic diversity in H. pylori decreases with geographic distance from east Africa, the cradle of modern humans. We also observe similar clines of genetic isolation by distance (IBD) for both H. pylori and its human host at a worldwide scale. Like humans, simulations indicate that H. pylori seems to have spread from east Africa around 58,000 yr ago. Even at more restricted geographic scales, where IBD tends to become blurred, principal component clines in H. pylori from Europe strongly resemble the classical clines for Europeans described by Cavalli-Sforza and colleagues7. Taken together, our results establish that anatomically modern humans were already infected by H. pylori before their migrations from Africa and demonstrate that H. pylori has remained intimately associated with their human host populations ever since.

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

Learn more

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

Figure 1: Five ancestral populations in H. pylori.
Figure 2: Parallel geographic patterns of genetic diversity in humans and H. pylori.
Figure 3: Similar clinal gradients between principal components 1–3 from European H. pylori and humans.

Similar content being viewed by others

References

  1. Achtman, M. et al. Recombination and clonal groupings within Helicobacter pylori from different geographical regions. Mol. Microbiol. 32, 459–470 (1999)

    Article  CAS  Google Scholar 

  2. Falush, D. et al. Traces of human migrations in Helicobacter pylori populations. Science 299, 1582–1585 (2003)

    Article  ADS  CAS  Google Scholar 

  3. Wirth, T. et al. Distinguishing human ethnic groups by means of sequences from Helicobacter pylori: lessons from Ladakh. Proc. Natl Acad. Sci. USA 101, 4746–4751 (2004)

    Article  ADS  CAS  Google Scholar 

  4. Eppinger, M. et al. Who ate whom? Adaptive Helicobacter genomic changes that accompanied a host jump from early humans to large felines. PLoS Genet. 2, e120 (2006)

    Article  Google Scholar 

  5. Kersulyte, D. et al. Differences in genotypes of Helicobacter pylori from different human populations. J. Bacteriol. 182, 3210–3218 (2000)

    Article  CAS  Google Scholar 

  6. Dailidiene, D. et al. Helicobacter acinonychis: genetic and rodent infection studies of a Helicobacter pylori-like gastric pathogen of cheetahs and other big cats. J. Bacteriol. 186, 356–365 (2004)

    Article  CAS  Google Scholar 

  7. Piazza, A. et al. Genetics and the origin of European languages. Proc. Natl Acad. Sci. USA 92, 5836–5840 (1995)

    Article  ADS  CAS  Google Scholar 

  8. Suerbaum, S. & Michetti, P. Helicobacter pylori infection. N. Engl. J. Med. 347, 1175–1186 (2002)

    Article  CAS  Google Scholar 

  9. Relethford, J. H. Global patterns of isolation by distance based on genetic and morphological data. Hum. Biol. 76, 499–513 (2004)

    Article  Google Scholar 

  10. Serre, D. & Paabo, S. Evidence for gradients of human genetic diversity within and among continents. Genome Res. 14, 1679–1685 (2004)

    Article  CAS  Google Scholar 

  11. Manica, A., Prugnolle, F. & Balloux, F. Geography is a better determinant of human genetic differentiation than ethnicity. Hum. Genet. 118, 366–371 (2005)

    Article  Google Scholar 

  12. Ramachandran, S. et al. Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. Proc. Natl Acad. Sci. USA 102, 15942–15947 (2005)

    Article  ADS  CAS  Google Scholar 

  13. Prugnolle, F., Manica, A. & Balloux, F. Geography predicts neutral genetic diversity of human populations. Curr. Biol. 15, R159–R160 (2005)

    Article  CAS  Google Scholar 

  14. Liu, H., Prugnolle, F., Manica, A. & Balloux, F. A geographically explicit genetic model of worldwide human-settlement history. Am. J. Hum. Genet. 79, 230–237 (2006)

    Article  CAS  Google Scholar 

  15. Cavalli-Sforza, L. L., Menozzi, P. & Piazza, A. The History and Geography of Human Genes (Princeton University Press, Princeton, New Jersey, 1994)

    MATH  Google Scholar 

  16. Rosenberg, N. A. et al. Clines, clusters, and the effect of study design on the inference of human population structure. PLoS Genet. 1, e70 (2005)

    Article  Google Scholar 

  17. Falush, D., Stephens, M. & Pritchard, J. K. Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164, 1567–1587 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Underhill, P. A. et al. Y chromosome sequence variation and the history of human populations. Nature Genet. 26, 358–361 (2000)

    Article  CAS  Google Scholar 

  19. Ingman, M. & Gyllensten, U. Analysis of the complete human mtDNA genome: methodology and inferences for human evolution. J. Hered. 92, 454–461 (2001)

    Article  CAS  Google Scholar 

  20. Zhivotovsky, L. A., Rosenberg, N. A. & Feldman, M. W. Features of evolution and expansion of modern humans, inferred from genomewide microsatellite markers. Am. J. Hum. Genet. 72, 1171–1186 (2003)

    Article  CAS  Google Scholar 

  21. Mellars, P. Why did modern human populations disperse from Africa ca. 60,000 years ago? A new model. Proc. Natl Acad. Sci. USA 103, 9381–9386 (2006)

    Article  ADS  CAS  Google Scholar 

  22. Currat, M. & Excoffier, L. The effect of the Neolithic expansion on European molecular diversity. Proc. Biol. Sci. 272, 679–688 (2005)

    Article  Google Scholar 

  23. Momynaliev, K. T. et al. Population identification of Helicobacter pylori isolates from Russia. Genetika 41, 1182–1185 (2005)

    CAS  Google Scholar 

  24. Rosenberg, N. A. DISTRUCT: a program for the graphical display of population structure. Mol. Ecol. Notes 4, 137–138 (2004)

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge the receipt of bacterial strains from A. van der Ende, M. J. Blaser, N. J. Saunders, R. J. Owen, F. Mégraud and sequences from K. T. Momynaliev and C. Kraft. We thank J. Goudet for providing a modified version of FSTAT able to deal with the large data set and help with R by K. -P. Pleissner. Grant support was from the German Federal Ministry for Education and Research (BMBF) in the framework of the PathoGenoMik Network (M.A., S.S.), the Biotechnology and Biological Sciences Research Council (F.B.), the Swedish Research council (T.W.) and Lund University Hospital (T.W.)

EMBL accession numbers for DNA sequences, AM413111–418360

Author information

Author notes

  1. Bodo Linz and François Balloux: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Biology, Max-Planck Institut für Infektionsbiologie, D-10117 Berlin, Germany,

    Bodo Linz, Yoshan Moodley, Philippe Roumagnac, Christiana Stamer & Mark Achtman

  2. Department of Genetics, Theoretical and Molecular Population Genetics Group, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK,

    François Balloux & Hua Liu

  3. Department of Zoology, Evolutionary Ecology Group, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK,

    Andrea Manica

  4. Department of Statistics, University of Oxford, Oxford OX1 3SY, UK,

    Daniel Falush

  5. Génétique et Evolution des Maladies Infectieuses, UMR IRD-CNRS 2724, centre IRD de Montpellier, 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 05, France,

    Franck Prugnolle

  6. Department of Internal Medicine and Gastroenterology, University of Pretoria, Pretoria 0002, South Africa,

    Schalk W. van der Merwe

  7. Department of Medicine–Gastroenterology, Baylor College of Medicine and Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA,

    Yoshio Yamaoka & David Y. Graham

  8. Department of Microbiology, Donostia Hospital, 20014 San Sebastian, Spain,

    Emilio Perez-Trallero

  9. Department of Laboratory Medicine, Lund University, SE22632 Lund, Sweden,

    Torkel Wadstrom

  10. Medizinische Hochschule Hannover, Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany,

    Sebastian Suerbaum

Authors
  1. Bodo Linz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. François Balloux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshan Moodley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrea Manica
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hua Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Philippe Roumagnac
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daniel Falush
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christiana Stamer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Franck Prugnolle
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Schalk W. van der Merwe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yoshio Yamaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. David Y. Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Emilio Perez-Trallero
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Torkel Wadstrom
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sebastian Suerbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Mark Achtman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to François Balloux, Sebastian Suerbaum or Mark Achtman.

Ethics declarations

Competing interests

EMBL accession numbers for DNA sequences, AM413111–418360. Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures S1-S6, Supplementary Methods, Supplementary Tables S1-S6 and additional references. (PDF 2386 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Linz, B., Balloux, F., Moodley, Y. et al. An African origin for the intimate association between humans and Helicobacter pylori. Nature 445, 915–918 (2007). https://doi.org/10.1038/nature05562

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05562

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

Advanced 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