From epigenetic landscape to phenotypic fitness landscape: evolutionary effect of pathogens on host traits

Abstract

The epigenetic landscape illustrates how cells differentiate into different types through the control of gene regulatory networks. Numerous studies have investigated epigenetic gene regulation but there are limited studies on how the epigenetic landscape and the presence of pathogens influence the evolution of host traits. Here we formulate a multistable decision-switch model involving many possible phenotypes with the antagonistic influence of parasitism. As expected, pathogens can drive dominant (common) phenotypes to become inferior, such as through negative frequency-dependent selection. Furthermore, novel predictions of our model show that parasitism can steer the dynamics of phenotype specification from multistable equilibrium convergence to oscillations. This oscillatory behavior could explain pathogen-mediated epimutations and excessive phenotypic plasticity. The Red Queen dynamics also occur in certain parameter space of the model, which demonstrates winnerless cyclic phenotype-switching in hosts and in pathogens. The results of our simulations elucidate how epigenetic landscape is associated with the phenotypic fitness landscape and how parasitism facilitates non-genetic phenotypic diversity.