Scholarlink

<p>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 (<i>n</i> = 2506) collection of Vietnamese <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) isolates, finding targets of selection to be lineage-specific, and encompass diverse functions, including dormancy (<i>Rv0080</i>), zinc homeostasis (<i>zur</i>), and virulence (ESX-1 structure). Extending our screen to the wider <i>Mtb</i> complex (MTBC) phylogeny demonstrated <i>Rv0080</i> to display an extraordinarily dynamic evolutionary history, acquiring premature stop codons or putative functional mutations on branches upstream of 8 of the 10 human-adapted lineages, and undergoing positive selection in the remaining 2. Lineage 1, which is one of two such lineages retaining the ancestral <i>Rv0080</i> sequence, displays a rate of selection for this gene (dN/dS=9.37) exceeding any other in the <i>Mtb</i> genome, save a transcription factor linked to its expression (<i>Rv0042c</i>; dN/dS=11.02). Deletion of <i>Rv0080</i>’s <i>M. smegmatis</i> orthologue confers a survival advantage in hypoxic conditions, as does the evolution of nonsense or missense mutations on an ancestral <i>Rv0080</i> background. We show the dormancy survival regulon experienced recurrent episodes of reductive evolution across the MTBC phylogeny, illuminating a novel mechanism via which it adapted to human populations.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dormancy regulon reduction was pivotal to the evolution of Mycobacterium tuberculosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月13日

查看全文
  • Matthew Silcocks,
  • James P. Lingford,
  • Chen-Yi Cheung,
  • William J. Jowsey,
  • Rita M. McCall,
  • Christopher D. Rae,
  • Liam K. Harold,
  • David Edwards,
  • Evan Pepper-Tunick,
  • Stephanie L. Neville,
  • Megan J. Maher,
  • Aleix Canalda-Baltrons,
  • Xuling Chang,
  • Phan Vuong Khac Thai,
  • Kathryn E. Holt,
  • Nitin S. Baliga,
  • Gregory M. Cook,
  • Thomas R. Hawn,
  • Nguyen Thuy Thuong Thuong,
  • Maxine Caws,
  • Chris Greening,
  • Christopher A. McDevitt,
  • Jeffery S. Cox,
  • Matthew B. McNeil,
  • Sarah J. Dunstan

摘要

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 upstream of 8 of the 10 human-adapted lineages, and undergoing positive selection in the remaining 2. Lineage 1, which is one of two such lineages retaining the ancestral Rv0080 sequence, displays a rate of selection for this gene (dN/dS=9.37) exceeding any other in the Mtb genome, save a transcription factor linked to its expression (Rv0042c; dN/dS=11.02). Deletion of Rv0080’s M. smegmatis orthologue confers a survival advantage in hypoxic conditions, as does the evolution of nonsense or missense mutations on an ancestral Rv0080 background. We show the dormancy survival regulon experienced recurrent episodes of reductive evolution across the MTBC phylogeny, illuminating a novel mechanism via which it adapted to human populations.