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

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    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.Fil: Muñoz Ramirez, Zilia Y.. INSTITUTO POLITÉCNICO NACIONAL (IPN);Fil: Pascoe, Ben. University of Bath; Reino UnidoFil: Mendez Tenorio, Alfonso. INSTITUTO POLITÉCNICO NACIONAL (IPN);Fil: Mourkas, Evangelos. University of Bath; Reino UnidoFil: Sandoval Motta, Santiago. Consejo Nacional de Ciencia y Tecnología; MéxicoFil: Perez Perez, Guillermo. New York University Langone Medical Center; Estados UnidosFil: Morgan, Douglas R.. University of Alabama at Birmingahm; Estados UnidosFil: Dominguez, Ricardo Leonel. Western Honduras Gastric Cancer Prevention Initiative Hospital de Occidente Santa Rosa de Copan; HondurasFil: Ortiz Princz, Diana. No especifíca;Fil: Cavazza, Maria Eugenia. No especifíca;Fil: Rocha, Gifone. Universidade Federal de Minas Gerais; BrasilFil: Queiroz, Dulcienne. Universidade Federal de Minas Gerais; BrasilFil: Catalano, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Zerbetto de Palma, Gerardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Goldman, Cinthia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Venegas, Alejandro. Universidad Diego Portales; ChileFil: Alarcon, Teresa. Universidad Autónoma de Madrid; EspañaFil: Oleastro, Monica. Universidade Nova de Lisboa; PortugalFil: Vale, Filipa F.. Universidade Nova de Lisboa; PortugalFil: Goodman, Karen J.. University of Alberta; CanadáFil: Torres, Roberto C.. Instituto Mexicano del Seguro Social; MéxicoFil: Berthenet, Elvire. Swansea University Medical School; Reino UnidoFil: Hitchings, Matthew D.. Swansea University Medical School; Reino UnidoFil: Blaser, Martin J.. Rutgers University; Estados UnidosFil: Sheppard, Samuel K.. University of Bath; Reino UnidoFil: Thorell, Kaisa. University of Gothenburg; SueciaFil: Torres, Javier. Instituto Mexicano del Seguro Social; Méxic

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

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    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.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.info:eu-repo/semantics/publishedVersio
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