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Diversity-Generating Retroelements in Prokaryotic Immunity.

ABSTRACT: Adaptive immunity systems found in different organisms fall into two major types. Prokaryotes possess CRISPR-Cas systems that recognize former invaders using memorized (captured) pieces of their DNA as pathogen signatures. Mammals possess a vast repertoire of antibodies and T-cell receptor variants generated in advance. In this second type of adaptive immunity, a pathogen presentation to the immune system specifically activates the cells that express matching antibodies or receptors. These cells proliferate to fight the infection and form the immune memory. The principle of preemptive production of diverse defense proteins for future use can hypothetically take place in microbes too. We propose a hypothesis that prokaryotes employ diversity-generating retroelements to prepare defense proteins against yet-unknown invaders. In this study, we test this hypothesis with the methods of bioinformatics and identify several candidate defense systems based on diversity-generating retroelements.

SUBMITTER: Belalov IS

PROVIDER: S-EPMC10053308 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Diversity-Generating Retroelements in Prokaryotic Immunity.

Belalov Ilya S IS Sokolov Arseniy A AA Letarov Andrey V AV

International journal of molecular sciences 20230315 6

Adaptive immunity systems found in different organisms fall into two major types. Prokaryotes possess CRISPR-Cas systems that recognize former invaders using memorized (captured) pieces of their DNA as pathogen signatures. Mammals possess a vast repertoire of antibodies and T-cell receptor variants generated in advance. In this second type of adaptive immunity, a pathogen presentation to the immune system specifically activates the cells that express matching antibodies or receptors. These cells ...[more]

PMID: 36982690

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Project description:BackgroundThe diversity-generating retroelements (DGRs) are a family of genetic elements that can produce mutations in target genes often related to ligand-binding functions, which possess a C-type lectin (CLec) domain that tolerates massive variations. They were first identified in viruses, then in bacteria and archaea from human-associated and environmental genomes. This DGR mechanism represents a fast adaptation of organisms to ever- changing environments. However, their existence, phylogenetic and structural diversity, and functions in a wide range of environments are largely unknown.ResultsHere we present a study of DGR systems based on metagenome-assembled genomes (MAGs) from host-associated, aquatic, terrestrial and engineered environments. In total, we identified 861 non-redundant DGR-RTs and ~ 5.7% are new. We found that microbes associated with human hosts harbor the highest number of DGRs and also exhibit a higher prevalence of DGRs. After normalizing with genome size and including more genome data, we found that DGRs occur more frequently in organisms with smaller genomes. Overall, we identified nine main clades in the phylogenetic tree of reverse transcriptases (RTs), some comprising specific phyla and cassette architectures. We identified 38 different cassette patterns and 6 of them were shown in at least 10 DGRs, showing differences in terms of the numbers, arrangements, and orientations of their components. Finally, most of the target genes were related to ligand-binding and signaling functions, but we discovered a few cases in which the VRs were situated in domains different from the CLec.ConclusionsOur research sheds light on the widespread prevalence of DGRs within environments and taxa, and supports the DGR phylogenetic divergence in different organisms. These variations might also occur in their structures since some cassette architectures were common in specific underrepresented phyla. In addition, we suggest that VRs could be found in domains different to the CLec, which should be further explored for organisms in scarcely studied environments.

Dataset Information

Diversity-Generating Retroelements in Prokaryotic Immunity.

Publications

Diversity-Generating Retroelements in Prokaryotic Immunity.

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