Distribution, Dynamics, and Diversity of the Antiphage Immune Systems in Prokaryotic Genomes and Metagenomes 

• Ano de defesa: 2024
• Autor(a) principal: Campos, Guillermo Uceda
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Ataques de fagos; Diversidade genômica; Genomic diversity; Metagenômica; Metagenomics; Phage attacks; Prokaryotic immune systems; Sistemas imunológicos procarióticos
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/95/95131/tde-10022025-103219/

Bacteria and Archaea employ several antiphage strategies, collectively known as prokaryotic immune systems, to defend against phage attacks. Initially focused on Restriction- Modification (RM), Abortive Infection (Abi), and CRISPR-Cas systems, recent discoveries have expanded this repertoire. This expansion has raised many questions about bacterial defense mechanisms, including the prevalence of these systems across prokaryotes, the causes of their diversity, and their origins and evolution. Despite of several studies, many aspects of these immune systems remain underexplored. Therefore, this research aims to analyze the distribution, dynamics and diversity of antiphage immune systems in prokaryotic genomes and metagenomes. A dataset of public genomes from the NCBI, along with metagenomic and metatranscriptomic datasets from a compost environment, was analyzed. A comprehensive pipeline was developed for data analysis, integrating various tools and techniques to genomics and metagenomics. Our key results revealed, firstly, that the distribution and diversity of immune systems across species are notable, not only for RM, Abi, and CRISPR-Cas, but also for the prevalence of lesser-known systems like Gabija, CBASS, Lamassu, and PD-T7 in over 60% of species. Interestingly, immune system patterns among bacterial species from different habitats or lifestyles reflected distinct immunity trends within those groups. Secondly, the extension of immune system detection in metagenomes to explore immune system dynamics revealed the presence of some systems over time in a compost environment, with CRISPR-Cas and RM Type I systems showing the highest persistence across time-series samples. Additionally, RNA-Seq data confirmed the activity of these immune systems, and taxonomic classification identified genera such as Streptomyces, Mycobacterium, and Thermobispora as the primary contributors to the immune systems detected over time, along with other genera. Finally, to delve into the organization of these immune systems, the analysis of protein domains uncovered distant phylogenetic relationships between systems and a wide array of combinations that contribute to the known diversity. Remote homology was identified across at least 45 immune system families, with RM systems appearing as a key point in the evolution and generation of other systems. The study also highlighted that helicase and ATPase domains frequently fuse with specific domains to create diverse immune systems. In conclusion, the computational analysis of antiphage immune systems in prokaryotic genomes and metagenomes offers a clear view of their complex diversity. This work not only opens avenues for further research into prokaryotic immunity but also deepens our understanding of prokaryote-phage interactions.