NLM DIR Seminar Schedule

Beyond canonical architectures: exploring hidden variation of prokaryotic defense systems

Prokaryotes rely on a diverse set of defense systems to protect themselves from phages and other mobile genetic elements. Many of these systems are modular, allowing conserved core machinery to be combined with alternative sensors, regulators, or effectors. These alternative architectures may be rare or confined to particular phylogenetic clades, making them difficult to detect with current annotation tools. To uncover such variants, we used a guilt-by-association approach to examine defense loci across 419,759 prokaryotic genomes. Our analysis identified 183 putative novel variants across 95 defense system types and showed that most are confined to coherent phylogenetic groups, consistent with their maintenance within particular lineages. Many of the associated genes encode proteins likely to function as regulators, infection sensors, or antiviral effectors. Experimental characterization of selected variants suggests that these accessory components can alter how a defense system functions and expand the range of phages it targets. Together, our findings reveal substantial hidden diversity within known defense systems and show that their functional variation extends beyond current definitions.

Satellite Phage Integrated Defensive and Ecotypic Replicons (SPIDERs).

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