Genomic determinants of speciation and spread of the Mycobacterium tuberculosis complex

• Published in: Science advances Vol. 5; no. 6; p. eaaw3307
• Main Authors: Chiner-Oms, Á., Sánchez-Busó, L., Corander, J., Gagneux, S., Harris, S. R., Young, D., González-Candelas, F., Comas, I.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.06.2019
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Datasets as Topic; Gene Expression; Genetic Loci; Genetic Speciation; Genetics; Genome, Bacterial; History, 21st Century; History, Ancient; Host-Pathogen Interactions - genetics; Humans; Microbiology; Mutation; Mycobacterium - classification; Mycobacterium - genetics; Mycobacterium - metabolism; Mycobacterium - pathogenicity; Mycobacterium tuberculosis - classification; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - metabolism; Mycobacterium tuberculosis - pathogenicity; Phylogeny; Recombination, Genetic; SciAdv r-articles; Selection, Genetic; Tuberculosis - epidemiology; Tuberculosis - genetics; Tuberculosis - history; Tuberculosis - microbiology; Virulence; Virulence Factors - genetics; Virulence Factors - metabolism
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.aaw3307

Emergence and global success of tuberculosis involve core pathogenesis functions under selection in epidemiological settings. Models on how bacterial lineages differentiate increase our understanding of early bacterial speciation events and the genetic loci involved. Here, we analyze the population genomics events leading to the emergence of the tuberculosis pathogen. The emergence is characterized by a combination of recombination events involving core pathogenesis functions and purifying selection on early diverging loci. We identify the phoR gene, the sensor kinase of a two-component system involved in virulence, as a key functional player subject to pervasive positive selection after the divergence of the Mycobacterium tuberculosis complex from its ancestor. Previous evidence showed that phoR mutations played a central role in the adaptation of the pathogen to different host species. Now, we show that phoR mutations have been under selection during the early spread of human tuberculosis, during later expansions, and in ongoing transmission events. Our results show that linking pathogen evolution across evolutionary and epidemiological time scales points to past and present virulence determinants.