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* Corresponding author 1 Génétique mycobactérienne 2 Institut Pasteur de la Guadeloupe 3 Institut Pasteur de Madagascar 4 Centre for Molecular Biology and Neuroscience and Institute of Microbiology 5 Génétique moléculaire, évolutive et médicale

Abstract : BACKGROUND: Mycobacterium tuberculosis complex species display relatively static genomes and 99.9% nucleotide sequence identity. Studying the evolutionary history of such monomorphic bacteria is a difficult and challenging task. PRINCIPAL FINDINGS: We found that single-nucleotide polymorphism SNP analysis of DNA repair, recombination and replication 3R genes in a comprehensive selection of M. tuberculosis complex strains from across the world, yielded surprisingly high levels of polymorphisms as compared to house-keeping genes, making it possible to distinguish between 80% of clinical isolates analyzed in this study. Bioinformatics analysis suggests that a large number of these polymorphisms are potentially deleterious. Site frequency spectrum comparison of synonymous and non-synonymous variants and Ka-Ks ratio analysis suggest a general negative-purifying selection acting on these sets of genes that may lead to suboptimal 3R system activity. In turn, the relaxed fidelity of 3R genes may allow the occurrence of adaptive variants, some of which will survive. Furthermore, 3R-based phylogenetic trees are a new tool for distinguishing between M. tuberculosis complex strains. CONCLUSIONS-SIGNIFICANCE: This situation, and the consequent lack of fidelity in genome maintenance, may serve as a starting point for the evolution of antibiotic resistance, fitness for survival and pathogenicity, possibly conferring a selective advantage in certain stressful situations. These findings suggest that 3R genes may play an important role in the evolution of highly clonal bacteria, such as M. tuberculosis. They also facilitate further epidemiological studies of these bacteria, through the development of high-resolution tools. With many more microbial genomes being sequenced, our results open the door to 3R gene-based studies of adaptation and evolution of other, highly clonal bacteria.

Autor: Tiago Dos Vultos - Olga Mestre - Jean Rauzier - Marcin Golec - Nalin Rastogi - Voahangy Rasolofo - Tone Tonjum - Christophe Sola

Fuente: https://hal.archives-ouvertes.fr/


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