Discovering Biological Conflict Systems Through Genome Analysis: Evolutionary Principles and Biochemical Novelty

Abstract

Biological replicators, from genes within a genome to whole organisms, are locked in conflicts. Comparative genomics has revealed a staggering diversity of molecular armaments and mechanisms regulating their deployment, collectively termed biological conflict systems. These encompass toxins used in inter- and intraspecific interactions, self/nonself discrimination, antiviral immune mechanisms, and counter-host effectors deployed by viruses and intragenomic selfish elements. These systems possess shared syntactical features in their organizational logic and a set of effectors targeting genetic information flow through the Central Dogma, certain membranes, and key molecules like NAD+. These principles can be exploited to discover new conflict systems through sensitive computational analyses. This has led to significant advances in our understanding of the biology of these systems and furnished new biotechnological reagents for genome editing, sequencing, and beyond. We discuss these advances using specific examples of toxins, restriction-modification, apoptosis, CRISPR/second messenger–regulated systems, and other enigmatic nucleic acid–targeting systems. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 5 is August 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Bacterial NLR-related proteins protect against phage

“…The N-terminal regions of bacterial NACHT proteins encode many enzymatic domains that have previously been associated with biological conflict, including nucleases (RNases and DNases), peptidases, and NAD + -targeting enzymes (TIR and Sirtuin) (Aravind et al, 2022). Other domains also include Effector Associated Domains, Death-like domains, RNA-binding domains, transcription regulatory domains, and nucleotide signalgenerating or degrading domains ( Table S1 and Supplementary Discussion).…”

Streptomyces umbrella toxin particles block hyphal growth of competing species

“…To comprehensively retrieve UmbC protein homologues, the PSI-BLAST program 62 was used for iterative searches against the NCBI non-redundant (nr) protein database until convergence, with a cut-off e -value of 0.005. The five upstream and five downstream gene neighbours of UmbC were extracted from the NCBI GenBank files for use in the gene neighbourhood analysis 63 . All protein neighbours were clustered based on their sequence similarities using the BLASTCLUST program, a BLAST score-based single-linkage clustering method ( https://ftp.ncbi.nih.gov/blast/documents/blastclust.html ).…”

Umbrella toxin particles produced by Streptomyces block mycelial growth of competing species

“…To comprehensively retrieve UmbC protein homologs, the PSI-BLAST program 59 was employed for iterative searches against the NCBI non-redundant (nr) protein database until convergence, with a cut-off e-value of 0.005. The five upstream and five downstream gene neighbors of UmbC were extracted from the NCBI GenBank files for use in the gene neighborhood analysis 60 . All protein neighbors were clustered based on their sequence similarities using the BLASTCLUST program, a BLAST score-based single-linkage clustering method (https://ftp.ncbi.nih.gov/blast/documents/blastclust.html).…”