The evolutionary advantage of heritable phenotypic heterogeneity

Abstract

Abstract Phenotypic plasticity is an evolutionary driving force in diverse biological processes, including the adaptive immune system, the development of neoplasms, and the persistence of pathogens despite drug pressure. It is essential, therefore, to understand the evolutionary advantage of an allele that confers on cells the ability to express a range of phenotypes. Here, we study the fate of a new mutation that allows the expression of multiple phenotypic states, introduced into a finite population of individuals that can express only a single phenotype. We show that the advantage of such a mutation depends on the degree of phenotypic heritability between generations, called phenotypic memory. We analyze the fixation probability of the phenotypically plastic allele as a function of phenotypic memory, the variance of expressible phenotypes, the rate of environmental changes, and the population size. We find that the fate of a phenotypically plastic allele depends fundamentally on the environmental regime. In constant environments, plastic alleles are advantageous and their fixation probability increases with the degree of phenotypic memory. In periodically fluctuating environments, by contrast, there is an optimum phenotypic memory that maximizes the probability of the plastic allele’s fixation. This same optimum memory also maximizes geometric mean fitness, in steady state. We interpret these results in the context of previous studies in an infinite-population framework. We also discuss the implications of our results for the design of therapies that can overcome persistence and, indirectly, drug resistance.