Survival of the unfittest: Metabolic trade-offs expose unforeseen benefits of plasmid carriage

Abstract

Population genetics theory defines fitness as reproductive success: Mutants reproducing faster than their wild-type counterpart are favoured by selection. Otherwise, the mutations are lost. Here I show thatunfitmutants can thrive when selection favours non-reproductive traits if they engage in a trade-off with fitness. I co-maintained two constructs ofEscherichia coli, with and without a non-transmissible plasmid, for more than 80 generations in competition assays that favoured yield. Plasmid carriage prompted a known metabolic trade-off in the bacterium between growth rate per capita—reproductive success—and yield. Importantly the plasmid carries a tetracycline-resistance gene,tet(36). By favouring yield, cells harbouring the plasmid preserved it without exposure to the antibiotic. Unsurprisingly, these cells outgrew their fitter plasmid-free competitor with trace low tetracycline concentrations. Fitness competition assays are widely used, but experimental validation of their underlying principle is rare. These assays are the ‘gold-standard’ in genetics, but my work suggests their reliability may be lower than previously thought.