Phenotypic heterogeneity implements a game theoretic mixed strategy in a clonal microbial population

Genetically identical cells in microbial populations often exhibit a remarkable degree of phenotypic heterogeneity even in homogenous environments. While such heterogeneity is often thought to be a bet-hedging strategy against unpredictable environments, evolutionary game theory also predicts phenotypic heterogeneity as a stable response to evolutionary \"hawk-dove\" games, in which rare strategies are favored over common ones. Here we provide experimental evidence for this game theoretic explanation in the context of the well-studied yeast GAL network. In an environment containing the two sugars glucose and galactose, the yeast GAL network displays stochastic bimodal activation. We show that genetic mutants playing the \"pure\" strategies of GAL-ON or GAL-OFF can each invade the opposite strategy when rare, indicating a hawk-dove game between the two. Consistent with the Nash equilibrium of an evolutionary game, the stable mix of pure strategists does not necessarily maximize the growth of the overall population. We also find that the wild type GAL network can invade populations of both pure strategists while remaining uninvasible by either. Taken together, our results provide experimental evidence that evolutionary hawk-dove games between identical cells can explain the phenotypic heterogeneity found in clonal microbial populations.