Homoplastic single nucleotide polymorphisms contributed to phenotypic diversity in Mycobacterium tuberculosis

Autor:	Tada Juthayothin, Nat Smittipat, Surakameth Mahasirimongkol, Katsushi Tokunaga, Wasna Viratyosin, Prasit Palittapongarnpim, Areeya Disratthakit, Pornpen Tantivitayakul, Wuthiwat Ruangchai
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	Lineage (genetic) Molecular biology Population Epitopes T-Lymphocyte lcsh:Medicine Single-nucleotide polymorphism medicine.disease_cause Microbiology Polymorphism Single Nucleotide Article Mycobacterium tuberculosis Intergenic region Medical research medicine Genetics Gene family Humans Tuberculosis education lcsh:Science Gene Phylogeny Mutation education.field_of_study Antigens Bacterial Multidisciplinary biology lcsh:R biology.organism_classification Phenotype Genes Bacterial lcsh:Q Transcription Initiation Site 5' Untranslated Regions Genome Bacterial
Zdroj:	Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-020-64895-4
Popis:	Homoplastic mutations are mutations independently occurring in different clades of an organism. The homoplastic changes may be a result of convergence evolution due to selective pressures. Reports on the analysis of homoplastic mutations in Mycobacterium tuberculosis have been limited. Here we characterized the distribution of homoplastic single nucleotide polymorphisms (SNPs) among genomes of 1,170 clinical M. tuberculosis isolates. They were present in all functional categories of genes, with pe/ppe gene family having the highest ratio of homoplastic SNPs compared to the total SNPs identified in the same functional category. Among the pe/ppe genes, the homoplastic SNPs were common in a relatively small number of homologous genes, including ppe18, the protein of which is a component of a promising candidate vaccine, M72/AS01E. The homoplastic SNPs in ppe18 were particularly common among M. tuberculosis Lineage 1 isolates, suggesting the need for caution in extrapolating the results of the vaccine trial to the population where L1 is endemic in Asia. As expected, homoplastic SNPs strongly associated with drug resistance. Most of these mutations are already well known. However, a number of novel mutations associated with streptomycin resistance were identified, which warrants further investigation. A SNP in the intergenic region upstream of Rv0079 (DATIN) was experimentally shown to increase transcriptional activity of the downstream gene, suggesting that intergenic homoplastic SNPs should have effects on the physiology of the bacterial cells. Our study highlights the potential of homoplastic mutations to produce phenotypic changes. Under selective pressure and during interaction with the host, homoplastic mutations may confer advantages to M. tuberculosis and deserve further characterization.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::49fbf5e3b0dddd2afb35cf7f575a1987 http://link.springer.com/article/10.1038/s41598-020-64895-4 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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