Recurrent gene conversions and subcluster-specific variants are associated with Mycobacterium tuberculosis adaptation to intensive host pressure: a comparative genomic study
4 affiliations
- 1Department of Infectious Diseases, Fuzong Clinical Medical College of Fujian Medical University
- 2Department of Infectious Diseases, 900th Hospital of PLA Joint Logistic Support Force
- 3Department of Clinical Laboratory Medicine, 900th Hospital of PLA Joint Logistic Support Force
- 4Medical Information Data Room, 900th Hospital of PLA Joint Logistic Support Force
Abstract
Background: Long-read sequencing has revealed complex variations, such as gene conversions in immunologically critical PE/PPE gene families, yet their role in Mycobacterium tuberculosis host adaptation remains unclear.
Methods: 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.
Results: 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.
Conclusion: These findings suggest a framework in which M. tuberculosis 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.
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BibTeX
@article{lin2026recurrent,
title = {{Recurrent gene conversions and subcluster-specific variants are associated with Mycobacterium tuberculosis adaptation to intensive host pressure: a comparative genomic study}},
author = {Tianyu Lin and Kun Chen and Zhenchun Chen and Yurou Jin and Weizhen Chen},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1950486},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1950486/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Recurrent gene conversions and subcluster-specific variants are associated with Mycobacterium tuberculosis adaptation to intensive host pressure: a comparative genomic study
AU - Tianyu Lin
AU - Kun Chen
AU - Zhenchun Chen
AU - Yurou Jin
AU - Weizhen Chen
PY - 2026
DA - 2026/10/07
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1950486
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1950486/full
AB - Background: Long-read sequencing has revealed complex variations, such as gene conversions in immunologically critical PE/PPE gene families, yet their role in Mycobacterium tuberculosis host adaptation remains unclear. Methods: 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. Results: 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. Conclusion: These findings suggest a framework in which M. tuberculosis 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.
SN - 1664-302X
ER -