Dormancy regulon reduction was pivotal to the evolution of Mycobacterium tuberculosis

M Silcocks; JP Lingford; CY Cheung; WJ Jowsey; RM McCall; CD Rae; LK Harold; D Edwards; E Pepper-Tunick; SL Neville; MJ Maher; A Canalda-Baltrons; X Chang; PVK Thai; KE Holt; NS Baliga; GM Cook; TR Hawn; NTT Thuong; M Caws; C Greening; CA McDevitt; JS Cox; MB McNeil; SJ Dunstan

Journal article

Dormancy regulon reduction was pivotal to the evolution of Mycobacterium tuberculosis

M Silcocks, JP Lingford, CY Cheung, WJ Jowsey, RM McCall, CD Rae, LK Harold, D Edwards, E Pepper-Tunick, SL Neville, MJ Maher, A Canalda-Baltrons, X Chang, PVK Thai, KE Holt, NS Baliga, GM Cook, TR Hawn, NTT Thuong, M Caws Show all

Nature Communications | Published : 2026

DOI: 10.1038/s41467-026-71566-x

Open access

Abstract

Phenotypically agnostic screens for positive selection in pathogen populations provide a means of pinpointing genes and regulatory regions involved in adaptation to the local environment or host population. We screened a large (n = 2506) collection of Vietnamese Mycobacterium tuberculosis (Mtb) isolates, finding targets of selection to be lineage-specific, and encompass diverse functions, including dormancy (Rv0080), zinc homeostasis (zur), and virulence (ESX-1 structure). Extending our screen to the wider Mtb complex (MTBC) phylogeny demonstrated Rv0080 to display an extraordinarily dynamic evolutionary history, acquiring premature stop codons or putative functional mutations on branches up..

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