The evolution of disease resistance and tolerance in spatially structured populations

The ubiquitous challenge from infectious disease has prompted the evolution of diverse host defenses, which can be divided into two broad classes: resistance (which limits pathogen growth and infection) and tolerance (which does not limit infection, but instead reduces or offsets its negative fitness consequences). Resistance and tolerance may provide equivalent short-term benefits, but have fundamentally different epidemiological consequences and thus exhibit different evolutionary behaviors. We consider the evolution of resistance and tolerance in a spatially structured population using a stochastic simulation model. We show that tolerance can invade a population of susceptible individuals (i.e., neither resistant nor tolerant) with higher cost than resistance, even though they each provide equivalent direct benefits to the host, because tolerant hosts impose higher disease burden upon vulnerable competitors. However, in spatially structured settings, tolerance can invade a population of resistant hosts only with lower cost than resistance due to spatial genetic structure and the higher local incidence of disease around invading tolerant individuals. The evolution of tolerance is therefore constrained by spatial genetic structure in a manner not previously revealed by nonspatially explicit models, suggesting mechanisms that could maintain variation or limit the occurrence of tolerance relative to resistance.