PMID- 33468705
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210202
IS  - 2379-5077 (Print)
IS  - 2379-5077 (Electronic)
IS  - 2379-5077 (Linking)
VI  - 6
IP  - 1
DP  - 2021 Jan 19
TI  - Comparative Genomic Analysis of Mycobacteriaceae Reveals Horizontal Gene 
      Transfer-Mediated Evolution of the CRISPR-Cas System in the Mycobacterium 
      tuberculosis Complex.
LID - 10.1128/mSystems.00934-20 [doi]
LID - e00934-20
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) and 
      CRISPR-associated (Cas) genes are conserved genetic elements in many prokaryotes, 
      including Mycobacterium tuberculosis, the causative agent of tuberculosis. 
      Although knowledge of CRISPR locus variability has been utilized in M. 
      tuberculosis strain genotyping, its evolutionary path in Mycobacteriaceae is not 
      well understood. In this study, we have performed a comparative analysis of 141 
      mycobacterial genomes and identified the exclusive presence of the CRISPR-Cas 
      type III-A system in M. tuberculosis complex (MTBC). Our global phylogenetic 
      analysis of CRISPR repeats and Cas10 proteins offers evidence of horizontal gene 
      transfer (HGT) of the CRISPR-Cas module in the last common ancestor of MTBC and 
      Mycobacterium canettii from a Streptococcus-like environmental bacterium. 
      Additionally, our results show that the variation of CRISPR-Cas organization in 
      M. tuberculosis lineages, especially in the Beijing sublineage of lineage 2, is 
      due to the transposition of insertion sequence IS6110 The direct repeat (DR) 
      region of the CRISPR-Cas locus acts as a hot spot for IS6110 insertion. We show 
      in M. tuberculosis H37Rv that the repeat at the 5' end of CRISPR1 of the forward 
      strand is an atypical repeat made up partly of IS-terminal inverted repeat and 
      partly CRISPR DR. By tracing an undetectable spacer sequence in the DR region, 
      the two CRISPR loci could theoretically be joined to reconstruct the ancestral 
      single CRISPR-Cas locus organization, as seen in M. canettii This study retracing 
      the evolutionary events of HGT and IS6110-driven genomic deletions helps us to 
      better understand the strain-specific variations in M. tuberculosis 
      lineages.IMPORTANCE Comparative genomic analysis of prokaryotes has led to a 
      better understanding of the biology of several pathogenic microorganisms. One 
      such clinically important pathogen is M. tuberculosis, the leading cause of 
      bacterial infection worldwide. Recent evidence on the functionality of the 
      CRISPR-Cas system in M. tuberculosis has brought back focus on these conserved 
      genetic elements, present in many prokaryotes. Our study advances understanding 
      of mycobacterial CRISPR-Cas origin and its diversity among the different species. 
      We provide phylogenetic evidence of acquisition of CRISPR-Cas type III-A in the 
      last common ancestor shared between MTBC and M. canettii, by HGT-mediated events. 
      The most likely source of HGT was an environmental Firmicutes bacterium. Genomic 
      mapping of the CRISPR loci showed the IS6110 transposition-driven variations in 
      M. tuberculosis strains. Thus, this study offers insights into events related to 
      the evolution of CRISPR-Cas in M. tuberculosis lineages.
CI  - Copyright (c) 2021 Singh et al.
FAU - Singh, Anoop
AU  - Singh A
AUID- ORCID: 0000-0003-0721-1479
AD  - Department of Zoology, University of Delhi, Delhi, India.
FAU - Gaur, Mohita
AU  - Gaur M
AD  - Department of Zoology, University of Delhi, Delhi, India.
FAU - Sharma, Vishal
AU  - Sharma V
AD  - Department of Zoology, University of Delhi, Delhi, India.
FAU - Khanna, Palak
AU  - Khanna P
AD  - Department of Zoology, University of Delhi, Delhi, India.
FAU - Bothra, Ankur
AU  - Bothra A
AD  - CSIR-IGIB, Sukhdev Vihar, New Delhi, India.
FAU - Bhaduri, Asani
AU  - Bhaduri A
AD  - Cluster Innovation Centre, University of Delhi, Delhi, India.
FAU - Mondal, Anupam Kumar
AU  - Mondal AK
AD  - CSIR-IGIB, Sukhdev Vihar, New Delhi, India.
FAU - Dash, Debasis
AU  - Dash D
AD  - CSIR-IGIB, Sukhdev Vihar, New Delhi, India.
FAU - Singh, Yogendra
AU  - Singh Y
AUID- ORCID: 0000-0002-3902-4355
AD  - Department of Zoology, University of Delhi, Delhi, India ysinghdu@gmail.com 
      richamisra@svc.ac.in.
FAU - Misra, Richa
AU  - Misra R
AD  - Department of Zoology, University of Delhi, Delhi, India ysinghdu@gmail.com 
      richamisra@svc.ac.in.
AD  - Department of Zoology, Sri Venkateswara College, University of Delhi, Delhi, 
      India.
LA  - eng
PT  - Journal Article
DEP - 20210119
PL  - United States
TA  - mSystems
JT  - mSystems
JID - 101680636
PMC - PMC7820667
OTO - NOTNLM
OT  - CRISPR-Cas system
OT  - IS6110
OT  - Mycobacterium
OT  - Mycobacterium canettii
OT  - Mycobacterium tuberculosis
OT  - comparative genomics
OT  - evolution
OT  - horizontal gene transfer
OT  - transposons
EDAT- 2021/01/21 06:00
MHDA- 2021/01/21 06:01
PMCR- 2021/01/19
CRDT- 2021/01/20 05:44
PHST- 2021/01/20 05:44 [entrez]
PHST- 2021/01/21 06:00 [pubmed]
PHST- 2021/01/21 06:01 [medline]
PHST- 2021/01/19 00:00 [pmc-release]
AID - 6/1/e00934-20 [pii]
AID - mSystems00934-20 [pii]
AID - 10.1128/mSystems.00934-20 [doi]
PST - epublish
SO  - mSystems. 2021 Jan 19;6(1):e00934-20. doi: 10.1128/mSystems.00934-20.