Informational architecture organizes plasmid genomes

Abstract

Plasmids are widely viewed as carriers of accessory genes, whereas molecular machineries required to replicate, transcribe and translate genetic information are thought to be encoded primarily by chromosomes. Yet, the recurrent presence of these central dogma-associated genes on plasmids raises a fundamental question of whether these genes merely represent incidental acquisitions or form coordinated informational components that support plasmid function. Here, by analyzing 61,961 plasmids spanning diverse prokaryotic lineages, we show that plasmid-encoded informational genes are not random cargos but form predictable architecture. Using plasmid-borne tRNAs as a model, we demonstrate that their presence, composition and abundance can be accurately inferred from surrounding plasmid gene content and are coupled to the codon demands of plasmid genes. Similar patterns extend to genes associated with replication, transcription, and translation, revealing coordinated informational organization across plasmid genomes. Together, these findings suggest that plasmids do not only encode adaptive functions but also propagate the infrastructure required to execute them, expanding the evolutionary role of horizontal gene transfer.