Detection of gene fusions in Mycobacterium tuberculosis using a genomics and proteomics approach in combination with the use of custom software

Mycobacterium tuberculosis is a facultative intracellular pathogen, responsible for causing the disease tuberculosis. The harsh environment in which M. tuberculosis survives requires this pathogen to maintain an evolutionary advantage. The apparent absence of horizontal gene transfer in M. tuberculosis, however, 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. Next, we further develop software that detects potential gene fusion events from multigene deletions using whole-genome sequencing data. Finally, we demonstrate expression of these gene fusions at the protein level using mass spectrometry. However, these events are rare compared to other genomic variations found within the M. tuberculosis genome. Gene fusions may provide an additional means of evolution for M. tuberculosis in its natural environment whereby novel proteins and functions can arise.