Evolutionary mechanisms that determine which bacterial genes are carried on plasmids

Abstract

Abstract The evolutionary pressures that determine the location (chromosomal or plasmid‐borne) of bacterial genes are not fully understood. We investigate these pressures through mathematical modeling 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: the higher the frequency of one form of resistance compared to the other, the higher its relative fitness. This 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—through either mutation or horizontal gene transfer—has time to increase in frequency and thus becomes difficult to displace. Higher rates of horizontal transfer of plasmid‐borne than chromosomal genes therefore predict moderately beneficial genes will be found on plasmids. Gene flow between plasmid and chromosome allows chromosomal forms to arise, but positive frequency‐dependent selection prevents these from establishing. Further modeling shows that this effect is particularly pronounced when genes are shared across a large number of species, suggesting that antibiotic resistance genes are often found on plasmids because they are moderately beneficial across many species. We also revisit previous theoretical work—relating to the role of local adaptation in explaining gene location and to plasmid persistence—in light of our findings.

Keywords

• Evolutionary genomics
• microbes
• models
• theory