Regulatory sequence-based discovery of anti-defense genes in archaeal viruses
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Regulatory sequence-based discovery of anti-defense genes in archaeal viruses. / Bhoobalan-Chitty, Yuvaraj; Xu, Shuanshuan; Martinez-Alvarez, Laura; Karamycheva, Svetlana; Makarova, Kira S.; Koonin, Eugene V.; Peng, Xu.
In: Nature Communications, Vol. 15, No. 1, 3699, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Regulatory sequence-based discovery of anti-defense genes in archaeal viruses
AU - Bhoobalan-Chitty, Yuvaraj
AU - Xu, Shuanshuan
AU - Martinez-Alvarez, Laura
AU - Karamycheva, Svetlana
AU - Makarova, Kira S.
AU - Koonin, Eugene V.
AU - Peng, Xu
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - In silico identification of viral anti-CRISPR proteins (Acrs) has relied largely on the guilt-by-association method using known Acrs or anti-CRISPR associated proteins (Acas) as the bait. However, the low number and limited spread of the characterized archaeal Acrs and Aca hinders our ability to identify Acrs using guilt-by-association. Here, based on the observation that the few characterized archaeal Acrs and Aca are transcribed immediately post viral infection, we hypothesize that these genes, and many other unidentified anti-defense genes (ADG), are under the control of conserved regulatory sequences including a strong promoter, which can be used to predict anti-defense genes in archaeal viruses. Using this consensus sequence based method, we identify 354 potential ADGs in 57 archaeal viruses and 6 metagenome-assembled genomes. Experimental validation identified a CRISPR subtype I-A inhibitor and the first virally encoded inhibitor of an archaeal toxin-antitoxin based immune system. We also identify regulatory proteins potentially akin to Acas that can facilitate further identification of ADGs combined with the guilt-by-association approach. These results demonstrate the potential of regulatory sequence analysis for extensive identification of ADGs in viruses of archaea and bacteria.
AB - In silico identification of viral anti-CRISPR proteins (Acrs) has relied largely on the guilt-by-association method using known Acrs or anti-CRISPR associated proteins (Acas) as the bait. However, the low number and limited spread of the characterized archaeal Acrs and Aca hinders our ability to identify Acrs using guilt-by-association. Here, based on the observation that the few characterized archaeal Acrs and Aca are transcribed immediately post viral infection, we hypothesize that these genes, and many other unidentified anti-defense genes (ADG), are under the control of conserved regulatory sequences including a strong promoter, which can be used to predict anti-defense genes in archaeal viruses. Using this consensus sequence based method, we identify 354 potential ADGs in 57 archaeal viruses and 6 metagenome-assembled genomes. Experimental validation identified a CRISPR subtype I-A inhibitor and the first virally encoded inhibitor of an archaeal toxin-antitoxin based immune system. We also identify regulatory proteins potentially akin to Acas that can facilitate further identification of ADGs combined with the guilt-by-association approach. These results demonstrate the potential of regulatory sequence analysis for extensive identification of ADGs in viruses of archaea and bacteria.
U2 - 10.1038/s41467-024-48074-x
DO - 10.1038/s41467-024-48074-x
M3 - Journal article
C2 - 38698035
AN - SCOPUS:85191974238
VL - 15
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3699
ER -
ID: 391675705