Non-conjugative plasmids limit their mobility to persist in nature

Plasmids are mobile genetic elements that disseminate beneficial genes, such as those conferring antibiotic resistance, but the evolutionary forces shaping their distribution remain unclear. This study challenges the idea that non-conjugative plasmids evolved for high-frequency spread. Using Staphylococcus aureus as a model, we found these plasmids lack key DNA sequences ("pac" or "cos" sites) essential for efficient phage-mediated transduction, despite such sequences not being costly. While S. aureus plasmids can evolve to enhance phage-mediated mobility by incorporating phage DNA, this strategy proves detrimental. In mixed populations, low plasmid transfer enables plasmids to co-exist and protect host bacteria and neighbors from threats. However, increased movement reduces plasmid diversity, eroding protective benefits and leaving populations vulnerable. Our findings indicate plasmids evolve to restrict movement, maintaining diversity and ensuring survival against threats like antibiotics and phages. This balance explains why plasmid mobility remains low in nature, despite their potential for rapid gene transfer.