Redefining paradigms in the archaeal virus-host arms race

Archaeal antiviral defense systems remain poorly characterized despite recent advances in understanding prokaryotic immunity. Here, we analyze 7,747 archaeal genomes, the largest and most diverse dataset to date, revealing a striking disparity in defense system prevalence and diversity compared to Bacteria. Nearly one-third of archaeal genomes lack known systems beyond CRISPR-Cas and restriction-modification (in contrast to only 2.2% bacterial genomes), and only 31% contain CRISPR-Cas systems, far below previous estimates. While many known defense systems appear restricted to Bacteria, several single-gene candidate systems (PDCs) are enriched in Archaea. Phylogenetic analyses suggest that PDC-S27, PDC-S70, and PDC-M05 likely originated in Archaea, representing rare archaeal contributions to the prokaryotic immune repertoire. Consistent with earlier studies, our findings support the existence of deep evolutionary links between archaeal and eukaryotic systems for argonautes and viperins. These analyses highlight both the underexplored nature and the evolutionary significance of archaeal immunity, calling for expanded efforts to uncover archaeal-specific systems and improve our understanding of immune evolution across domains of life.