Universal rules govern plasmid copy number

Plasmids –autonomously replicating DNA molecules– exhibit a broad range of replication and mobility strategies, genetic repertoires, host ranges, sizes, and copies per cell. However, the determinants of plasmid copy number (PCN) remain poorly understood. Here, we use extensive DNA sequencing data to analyse the copy number of thousands of diverse bacterial plasmids in a comprehensive manner. We find that PCN is highly variable, spanning nearly three orders of magnitude, and that it is intrinsically robust against changes in genomic context. We further show that PCN variability is tightly associated with plasmid lifestyles, and propose the concept of replicon dominance to explain interactions in widespread multi-replicon plasmids. Finally, we uncover a universal scaling law that links copy number and plasmid size across bacterial species, indicating that pervasive constraints modulate the PCN-size trade-off.