Evolutionary mechanisms that determine which bacterial genes are carried on plasmids

The evolutionary pressures that determine the location (chromosomal or plasmid-borne) of bacterial genes are not fully understood. We investigate these pressures through mathematical modelling in the context of antibiotic resistance, which is often found on plasmids. Our central finding is that gene location is under positive frequency-dependent selection, which can keep moderately beneficial genes on plasmids, despite occasional plasmid loss. For these genes, positive frequency-dependence leads to a priority effect: whichever form is acquired first has time to increase in frequency and thus become difficult to displace. We therefore propose that some traits, including antibiotic resistance, are found on plasmids because they are typically acquired on plasmids. Gene flow between plasmid and chromosome allows chromosomal forms to arise, but positive frequency-dependent selection prevents these from establishing. We also re-visit some previous theory in light of our results, with implications for plasmid persistence and the role of local adaptation in plasmid dynamics.