{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:49:33Z","timestamp":1791355773531,"version":"4.3.1"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Long-read sequencing has revealed complex variations, such as gene conversions in immunologically critical PE\/PPE gene families, yet their role in\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      host adaptation remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a comparative genomic analysis across a gradient of host-imposed selective pressure: chronic within-host infection, latent household transmission, and a 21-year clonal outbreak in Bern, Switzerland.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed a constrained accumulation of mutational events across distinct epidemiological settings, with rates ranging from 0.36 to 0.81 events per genome per year. Under minimal host-imposed selection, the pathogen accumulated only small-scale variants (i.e., SNPs and indels). During the outbreak, however, the genetic diversity landscape shifted toward larger-scale variants, including recurrent gene conversions and structural variations. Notably, an early PPE19-to-PPE18 conversion emerged in the ancestral strain and was maintained across the entire lineage. In contrast, 86% of variants were transient singletons, with only a small proportion persisting under selection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings suggest a framework in which\n                      <jats:italic>M. tuberculosis<\/jats:italic>\n                      maintains genomic stability through purifying selection, while retaining the capacity to generate adaptive diversity through large-scale genetic rearrangements in immunologically relevant genomic features under intensified host pressure.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1950486","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:50:47Z","timestamp":1791352247000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Recurrent gene conversions and subcluster-specific variants are associated with Mycobacterium tuberculosis adaptation to intensive host pressure: a comparative genomic study"],"prefix":"10.3389","volume":"17","author":[{"given":"Tianyu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Department of Infectious Diseases, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenchun","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical Information Data Room, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurou","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Department of Infectious Diseases, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Department of Infectious Diseases, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"RP97870","DOI":"10.7554\/elife.97870.4","article-title":"The Mycobacterium tuberculosis complex pangenome is small and shaped by sub-lineage-specific regions of difference","volume":"13","author":"Behruznia","year":"2025","journal-title":"eLife"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1186\/s12864-015-2067-2","article-title":"Whole genome sequencing reveals genomic heterogeneity and antibiotic purification in Mycobacterium tuberculosis isolates","volume":"16","author":"Black","year":"2015","journal-title":"BMC Genomics"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1986","DOI":"10.1056\/nejmc1505196","article-title":"Acquired resistance to bedaquiline and delamanid in therapy for tuberculosis","volume":"373","author":"Bloemberg","year":"2015","journal-title":"N. 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