Helicobacter pylori Genome Aggregation Database reveals complex evolutionary forces shaping its genomic landscape and clinical impact in East Asia

Helicobacter pylori Genome Aggregation Database reveals complex evolutionary forces shaping its genomic landscape and clinical impact in East Asia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Helicobacter pylori Genome Aggregation Database reveals complex evolutionary forces shaping its genomic landscape and clinical impact in East Asia Guanglin He, Lintao Luo, Xiaoqiong Tang, Hao Chen, Yunhui Liu, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7366252/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract We assembled HPgnomAD, a comprehensive global genome aggregation database of Helicobacter pylori (H. pylori) featuring 7,544 high-quality genomes from 278 populations, along with the first species-wide haplotype reference panel for genotype imputation. The panel provides high accuracy across diverse H. pylori populations, including those from low-coverage data, and is openly accessible with integrated analysis tools ( https://www.hpgnomad.top/ ). Variant discovery revealed 1.82 million SNPs and 0.65 million InDels, with African strains exhibiting the most tremendous diversity and East Asian strains showing unexpectedly high novel variation. Fine-scale analysis of the hpEAsia lineage revealed six new sublineages shaped by altitude-, latitude-related divergence and region-specific admixture. Phylogenomic dating revealed two divergence waves in East Asia, paralleling Upper Paleolithic settlement and Neolithic human expansions, with highland–lowland separation at ~18.8 kya, followed by the formation of complex geography-related population substructures. Genome-wide scans revealed adaptive loci related to metal acquisition, nitrogen metabolism, surface adhesion, and membrane transport, including altitude-associated highly differentiated variants linked to antibiotic resistance and gastric disease. By integrating genomic, evolutionary, environmental, and clinical data, HPgnomAD offers a framework for understanding H. pylori evolution, host‒pathogen adaptation, and precision medicine worldwide. Biological sciences/Evolution/Evolutionary genetics Health sciences/Pathogenesis Biological sciences/Evolution/Coevolution Full Text Additional Declarations There is NO Competing Interest. Supplementary Files ExtendedDataTable.xlsx Extended Data Tables ExtendedDataFigs.pdf Extended Data Figs Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7366252","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":506482264,"identity":"8842b54d-1291-4d1f-8834-a722c4665f6c","order_by":0,"name":"Guanglin 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