A 500-year tale of co-evolution, adaptation, and virulence: Helicobacter pylori in the Americas

Zilia Y. Muñoz-ramirez, Ben Pascoe, Alfonso Mendez-tenorio, Evangelos Mourkas, Santiago Sandoval-motta, Guillermo Perez-perez, Douglas R. Morgan, Ricardo Leonel Dominguez, Diana Ortiz-princz, Maria Eugenia Cavazza, Gifone Rocha, Dulcienne M. M. Queiroz, Mariana Catalano, Gerardo Zerbeto De La Palma, Cinthia G. Goldman, Alejandro Venegas, Teresa Alarcon, Monica Oleastro, Filipa F. Vale, Karen J. GoodmanRoberto C. Torres, Elvire Berthenet, Matthew D. Hitchings, Martin J. Blaser, Samuel K. Sheppard, Kaisa Thorell, Javier Torres

Research output: Contribution to journalArticlepeer-review

20 Citations (SciVal)


Helicobacter pylori is a common component of the human stomach microbiota, possibly dating back to the speciation of Homo sapiens. A history of pathogen evolution in allopatry has led to the development of genetically distinct H. pylori subpopulations, associated with different human populations, and more recent admixture among H. pylori subpopulations can provide information about human migrations. However, little is known about the degree to which some H. pylori genes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzed H. pylori genomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723 H. pylori strains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contributions from H. pylori populations originating in the Americas as well as other continents. Despite the complex admixture, distinctive genomic fingerprints were identified for each region, revealing novel American H. pylori subpopulations. A pan-genome Fst analysis showed that variation in virulence genes had the strongest fixation in America, compared with non-American populations, and that much of the variation constituted non-synonymous substitutions in functional domains. Network analyses suggest that these virulence genes have followed unique evolutionary paths in the American populations, spreading into different genetic backgrounds, potentially contributing to the high risk of gastric cancer in the region.
Original languageEnglish
Pages (from-to)78-92
Number of pages15
JournalISME Journal
Issue number1
Early online date2 Sept 2020
Publication statusPublished - 31 Jan 2021

Bibliographical note

Funding Information:
Acknowledgements This work was supported by “Consejo Nacional de Ciencia y Tecnología” (CONACYT; no. 576951) grant to ZYM-R, and by Magnus Bergvalls Foundation and Swedish Society for Medical Research (SSMF) to KT. SKS and BP are funded by the Medical Research Council (MR/L015080/1). Supported in part by the US National Cancer Institute National Cancer Institute to DRM (P01 CA028842, R01 CA190612, K07 CA125588, P30 CA068485). We are very grateful to Daniel Falush (Unit of Statistical Genetics of Bacteria, Institut Pasteur of Shanghai) for his critical input during the analysis of the presented data. We acknowledge the Aklavik H. pylori Project Planning Committee (Northwest Territories, Canada) for providing input on our presentation of this analysis.

Publisher Copyright:
© 2020, The Author(s).

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics


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