Gallant James, Mouton Jomien, Ummels Roy, Ten Hagen-Jongman Corinne, Kriel Nastassja, Pain Arnab, Warren Robin M, Bitter Wilbert, Heunis Tiaan, Sampson Samantha L
DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Science, Faculty of Medicine and Health Science, Stellenbosch University, Tygerberg, Cape Town 7505, South Africa.
Section of Molecular Microbiology, Amsterdam Institute for Molecules, Medicines and Systems, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands.
NAR Genom Bioinform. 2020 May 18;2(2):lqaa033. doi: 10.1093/nargab/lqaa033. eCollection 2020 Jun.
is a facultative intracellular pathogen responsible for causing tuberculosis. The harsh environment in which survives requires this pathogen to continuously adapt in order to maintain an evolutionary advantage. However, the apparent absence of horizontal gene transfer in 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 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 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 in its natural environment whereby novel chimeric proteins and functions can arise.
是一种导致结核病的兼性细胞内病原体。其生存的恶劣环境要求这种病原体不断适应，以保持进化优势。然而，在中明显缺乏水平基因转移，这限制了进化发生的方式。基因组的大规模变化可通过基因组缩减、重组事件和结构变异引入。在这里，我们在基因座中鉴定出一种功能性嵌合蛋白，已知其缺失会对蛋白质分泌和毒力产生影响。为了研究这种病原体是否更频繁地使用这种方法，我们进一步开发了软件，该软件使用全基因组测序数据从多基因缺失中检测潜在的基因融合事件。使用该软件，我们可以在分离株的基因组中识别出许多其他推定的基因融合事件。我们能够使用质谱法在蛋白质水平上证明这些基因融合之一的表达。因此，基因融合可能为在其自然环境中的进化提供一种额外的方式，由此可以产生新的嵌合蛋白和功能。
