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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:p>\n                    The underlying factors that lead to specific strains within a species to emerge as human pathogens remain mostly enigmatic. The diarrheal disease cholera is caused by strains from a phylogenetically confined group within the\n                    <jats:italic toggle=\"yes\">Vibrio cholerae<\/jats:italic>\n                    species, the pandemic cholera group (PCG), making it an ideal model system to tackle this puzzling phenomenon. Comprehensive analyses of over 1,840\n                    <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                    genomes, including environmental isolates from this study, reveal that the species consists of eleven groups, with the PCG belonging to the largest and located within a lineage shared with environmental strains. This hierarchical classification provided us with a framework to unravel the ecoevolutionary dynamics of the genetic determinants associated with the emergence of toxigenic\n                    <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                    . Our analyses indicate that this phenomenon is largely dependent on the acquisition of unique modular gene clusters and allelic variations that confer a competitive advantage during intestinal colonization. We determined that certain PCG-associated alleles are essential for successful colonization whereas others provide a nonlinear competitive advantage, acting as a critical bottleneck that clarifies the isolated emergence of PCG. For instance, toxigenic strains encoding non-PCG alleles of a)\n                    <jats:italic toggle=\"yes\">tcpF<\/jats:italic>\n                    or b) a sextuple allelic exchange mutant for genes\n                    <jats:italic toggle=\"yes\">tcpA<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">toxT<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">VC0176<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">VC1791<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">rfbT,<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">ompU<\/jats:italic>\n                    , lose their ability to colonize the intestine. Interestingly, these alleles do not play a role in the colonization of newly established model environmental reservoirs. Our study uncovers the evolutionary roots of toxigenic\n                    <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                    offering a tractable approach for investigating the emergence of pathogenic clones within an environmental population.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2417915122","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T11:06:42Z","timestamp":1748430402000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Allelic variations and gene cluster modularity act as nonlinear bottlenecks for cholera emergence"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3996-6780","authenticated-orcid":false,"given":"Mario","family":"L\u00f3pez-P\u00e9rez","sequence":"first","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central","place":["Florida, Orlando, 32827"]},{"name":"Microbial Genomics and Evolution Group, Divisi\u00f3n de Microbiolog\u00eda, Universidad Miguel Hern\u00e1ndez","place":["Alicante"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central","place":["Florida, Orlando, 32827"]},{"name":"Division of Molecular Microbiology, Department of Host-Microbe Interactions, St. Jude Children\u2019s Research Hospital","place":["Memphis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6267-2220","authenticated-orcid":false,"given":"Alicia","family":"Campos-Lopez","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central","place":["Florida, Orlando, 32827"]},{"name":"Microbial Genomics and Evolution Group, Divisi\u00f3n de Microbiolog\u00eda, Universidad Miguel Hern\u00e1ndez","place":["Alicante"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole","family":"Crist","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central","place":["Florida, Orlando, 32827"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudy-Ann","family":"Grant","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central","place":["Florida, Orlando, 32827"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2113-9269","authenticated-orcid":false,"given":"Jose M.","family":"Haro-Moreno","sequence":"additional","affiliation":[{"name":"Microbial Genomics and Evolution Group, Divisi\u00f3n de Microbiolog\u00eda, Universidad Miguel Hern\u00e1ndez","place":["Alicante"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0913-1093","authenticated-orcid":false,"given":"Asier","family":"Zaragoza-Solas","sequence":"additional","affiliation":[{"name":"Microbial Genomics and Evolution Group, Divisi\u00f3n de Microbiolog\u00eda, Universidad Miguel Hern\u00e1ndez","place":["Alicante"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1121-1204","authenticated-orcid":false,"given":"Salvador","family":"Almagro-Moreno","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central","place":["Florida, Orlando, 32827"]},{"name":"Division of Molecular Microbiology, Department of Host-Microbe Interactions, St. Jude Children\u2019s Research Hospital","place":["Memphis"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003652","article-title":"What factors might have led to the emergence of Ebola in West Africa?","volume":"9","author":"Alexander K. 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