Full text loading...
Chapter 16 : Mycobacterial Evolution: Insights from Genomics and Population Genetics
Category: Bacterial Pathogenesis; Microbial Genetics and Molecular Biology
Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase
Mycobacterium tuberculosis is an obligate human pathogen that is transmitted by aerosol from patients with pulmonary tuberculosis. Until recently, the evolution of tuberculosis remained largely in the realms of speculation. However, the genomics revolution has had the same dramatic effect on the study of M. tuberculosis as it has had on the study of other bacterial pathogens. This chapter has been structured around the different genetic approaches that are providing insights into the evolution of M. tuberculosis and have specifically emphasized important new findings emerging from recent studies of population genetics. A more complete understanding of the evolution of pathogenic mycobacteria will ultimately require definition of the genomic changes that accompanied the transition to a pathogenic lifestyle. One of the most significant genetic observations with relevance to understanding the evolution of M. tuberculosis has been the lack of single nucleotide polymorphisms (SNPs) detected among clinical isolates of M. tuberculosis. Recently, phylogenies based on large sequence polymorphisms (LSPs) or SNPs have confirmed that M. canettii is deeply branched from the other M. tuberculosis complex members. Until recently, however, there was little formal effort to understand M. tuberculosis from an evolutionary perspective. Recent advances in genomics now make it possible to explore the evolution of M. tuberculosis.
Phylogeny of slow-growing Mycobacterium based on 16S rRNA sequences (adapted from reference 146 ). Phylogenetic distances are not precise. Species that are underlined correspond to the obligate human pathogens. The Mycobacterium tuberculosis complex corresponds to M. tuberculosis, M. microti, M. africanum, M. bovis, M. caprae, and M. canettii, which have identical 16S rRNA sequences.
Large sequence polymorphisms in the epoxide hydrolase locus of three M. tuberculosis complex strains. The large rectangular boxes correspond to the DNA fragment absent from each strain, with the precise H37Rv genome coordinates marking the extent of each deletion. Deletions 236 and 236A were detected in strains isolated from San Francisco, and RD8 was originally detected in M. bovis BCG strains ( 7 , 59 ). The distinct end points for each polymorphism indicate that these genomic deletions have occurred independently. The annotation is according to the H37Rv sequence ( 27 ): Rv 3618, function unknown; ephA, epoxide hydrolase; esxV and esxW, members of the early secretory antigen family; PPE65 and PE32, members of two large gene families of unknown function; lpqG, lipoprotein; and hpt, involved in purine salvage.
Phylogeographical structure of reactivating M. tuberculosis strains in San Francisco. The phylogeny was constructed by maximum parsimony using large sequence polymorphisms detected by microarray analysis. The place of birth of the source case for each strain is shown on the right. White, crossed, black, and lined shadings have been superimposed, corresponding to East Asia, the Philippines, the Americas, or other places of birth, to reveal distinct geographical clades.
Sizes of complete or nearly complete mycobacterial genome sequences
Selected experimentally defined virulence factors of M. tuberculosis a