Regulatory sequence-based discovery of anti-defense genes in archaeal viruses
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- Fulltext
Final published version, 1.38 MB, PDF document
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.
Original language | English |
---|---|
Article number | 3699 |
Journal | Nature Communications |
Volume | 15 |
Issue number | 1 |
Number of pages | 13 |
ISSN | 2041-1723 |
DOIs | |
Publication status | Published - 2024 |
Bibliographical note
Publisher Copyright:
© The Author(s) 2024.
ID: 391675705