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Homoplastic single nucleotide polymorphisms contributed to phenotypic diversity in Mycobacterium tuberculosis
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Document Title
Homoplastic single nucleotide polymorphisms contributed to phenotypic diversity in Mycobacterium tuberculosis
Author
Tantivitayakul P., Ruangchai W., Juthayothin T., Smittipat N., Disratthakit A., Mahasirimongkol S., Viratyosin W., Tokunaga K., Palittapongarnpim P.
Name from Authors Collection
Scopus Author ID
56874822000
Affiliations
Department of Oral Microbiology, Faculty of Dentistry, Mahidol University, 6 Yothi Road, Bangkok, Thailand; Pornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, Thailand; National Centre for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Phaholyothin Road, Pathumthani, Thailand; Department of Medical Sciences, Ministry of Public Health, Tiwanon Road, Nonthaburi, Thailand; Department of Human Genetics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
Type
Article
Source Title
Scientific Reports
ISSN
20452322
Year
2020
Volume
10
Issue
1
Open Access
Gold, Green
Publisher
Nature Research
DOI
10.1038/s41598-020-64895-4
Abstract
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. © 2020, The Author(s).
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
Japan Agency for Medical Research and Development; Mahidol University; Ministry of Public Health; Japan International Cooperation Agency; Science and Technology Research Partnership for Sustainable Development
License
CC BY
Rights
Author
Publication Source
Scopus