2018 / 02

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DOI: 10.24075/brsmu.2018.016

REVIEW

CRISPR-Сas systems of Mуcоbacterium tuberculosis: the structure, transformation in different lineages in the process of evolution and a possible role in the formation of virulence and drug resistance

Zaychikova MV1, Zakharevich NV1, Chekalina MS, Danilenko VN1,2
About authors

1 Vavilov Institute of General Genetics, RAS, Moscow

2 Department of Bioinformatics, Faculty of Biological and Medical Physics,
Moscow Institute of Physics and Technology (State University), Dolgoprudny

Correspondence should be addressed: Marina Zaychikova
ul. Gubkina 3, Moscow, 119991; ur.xednay@51zaniram, ur.ggiv@direlav

Received: 2018-03-15 Accepted: 2018-03-20 Published online: 2018-06-09
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Fig. 1. The schematic representation of the phylogeny of the described М. tuberculosis lineages [33]
Fig. 2. Schematic of CRISPR-Cas structure in M. tuberculosis exemplified by the strain H37Rv. LS is leader sequence
Fig. 3. The structure of the CRISPR-Cas system of the М. tuberculosis Beijing lineage.
Ten highly conserved spacers shared by all M. tuberculosis lineages are located at the end of the CRISPR2 array distal to the leader sequence and are ancestral spacers mirroring the ancient state of CRISPR immunity [10]. More recent spacers are located next to the leader sequence
Fig. 4.Evolution of the CRISPR array in the M. tuberculosis Beijing lineage.
After the first 10 spacers of the CRISPR2 array had been integrated (they are the most ancient ones), the Euro-American and Beijing lines separated. The spacers SpB11-SpB14 of the Beijing lineage are not identical to the spacers Sp11-Sp14 found in other M. tuberculosis lineages. Due to the loss of cas1 and cas2 genes involved in the integration of new spacers, formation of the CRISPR2 array probably stopped. The CRISPR-Cas structure of the Beijing lineage has remained intact for a long time, but its youngest sublineage B0/W-148 demonstrates a loss of 4 spacers SpB11- SpB14 that are the array’s most recent acquisitions
Fig. 5. Phylogenetic profiles of genes found in the genomes of different M. tuberculosis lineages and strains.
Each line contains gene ID, the number of genomes with an orthologous gene and the PP of the gene; spaces represent missing genes. А. PP of cas-genes of M. tuberculosis H37Rv: сas2 (Rv2816c), сas1 (Rv2817c), сsm6 (Rv2818c), and сsm5 (Rv2819c). B. PP of candidate functionally related partners of M. tuberculosis cas-genes in the genome of the H37Rv strain. C. PP of genes putatively involved in the formation of compensatory mechanisms in the genome of the ССDC5079 strain (the Beijing lineage) following the loss of some CRISPR-Cas parts
Table 1. The comparative analysis of cas-genes found in 6 different lineages and one sublineage of M. tuberculosis
Note: * — represents percent identity computed in BLAST (https://blast.ncbi.nlm.nih.gov/Blast.cgi).
Table 2. Characteristics of functional partner candidates and genes involved in the compensatory mechanisms for CRISPR-Cas systems*
Note: * — only annotated genes are presented in this table; other genes code for hypothetical proteins with unknown functions (Rv1761c and CFBS_RS10335, CFBS_RS10345, CFBS_RS10350, CFBS_RS10355, CFBS_RS21395) or, as with Rv0071, are a mobile self-splicing retro-element, the so-called group II intron.