Identification of gene fusion events in Mycobacterium tuberculosis that encode chimeric proteins

James Gallant, Jomien Mouton, Roy Ummels, Corinne ten Hagen-Jongman, Nastassja Kriel, Arnab Pain, Robin M Warren, Wilbert Bitter, Tiaan Heunis, Samantha L Sampson

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Abstract Mycobacterium tuberculosis is a facultative intracellular pathogen responsible for causing tuberculosis. The harsh environment in which M. tuberculosis survives requires this pathogen to continuously adapt in order to maintain an evolutionary advantage. However, the apparent absence of horizontal gene transfer in M. tuberculosis imposes restrictions in the ways by which evolution can occur. Large-scale changes in the genome can be introduced through genome reduction, recombination events and structural variation. Here, we identify a functional chimeric protein in the ppe38–71 locus, the absence of which is known to have an impact on protein secretion and virulence. To examine whether this approach was used more often by this pathogen, we further develop software that detects potential gene fusion events from multigene deletions using whole genome sequencing data. With this software we could identify a number of other putative gene fusion events within the genomes of M. tuberculosis isolates. We were able to demonstrate the expression of one of these gene fusions at the protein level using mass spectrometry. Therefore, gene fusions may provide an additional means of evolution for M. tuberculosis in its natural environment whereby novel chimeric proteins and functions can arise.
Original languageEnglish (US)
JournalNAR Genomics and Bioinformatics
Volume2
Issue number2
DOIs
StatePublished - May 18 2020

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): BAS/1/1020-01-01
Acknowledgements: National Research Foundation/Vrije Universiteit Amsterdam Desmond Tutu Doctoral Training Program [to J.G.]; Financial support was provided by the South African Medical Research Council Centre for Tuberculosis Research and DST/NRF Centre of Excellence for Biomedical Tuberculosis Research [to S.S, J.G, J.M, N.K]; South African Research Chairs Initiative of the Department of Science and
Technology and National Research Foundation (NRF) of South Africa [UID 86539 to S.S.]; KAUST faculty baseline grant [BAS/1/1020-01-01 to A.P.]. Conflict of interest statement. None declared.

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