Abstract
Epigenetic switches are bistable, molecular systems built from self-reinforcing feedback loops that can spontaneously switch between heritable phenotypes in the absence of DNA mutation. It has been hypothesized that epigenetic switches first evolved as a mechanism of bet-hedging and adaptation, but the evolutionary trajectories and conditions by which an epigenetic switch can outcompete adaptation through genetic mutation remain unknown. Here, we used computer simulations to evolve a mechanistic, biophysical model of a self-activating genetic circuit, which can both adapt genetically through mutation and exhibit epigenetic switching. We evolved these genetic circuits under a fluctuating environment that alternatively selected for low and high protein expression levels. In all tested conditions, the population first evolved by genetic mutation towards a region of genotypes where genetic adaptation can occur faster after each environmental transition. Once in this region, the self-activating genetic circuit can exhibit epigenetic switching, which starts competing with genetic adaptation. We show a trade-off between either minimizing the adaptation time or increasing the robustness of the phenotype to biochemical noise. Epigenetic switching was superior in a fast fluctuating environment because it adapted faster than genetic mutation after an environmental transition, while still attenuating the effect of biochemical noise on the phenotype. Conversely, genetic adaptation was favored in a slowly fluctuating environment because it maximized the phenotypic robustness to biochemical noise during the constant environment between transitions, even if this resulted in slower adaptation. This simple trade-off predicts the conditions and trajectories under which an epigenetic switch evolved to outcompete genetic adaptation, shedding light on possible mechanisms by which bet-hedging strategies might emerge and persist in natural populations.
Highlights
Populations often need to adapt to environmental changes in order to survive
Epigenetic switches regulate cell fate decisions during development in multicellular organisms, but their origin predates multicellularity because they are found in viruses, bacteria, and unicellular eukaryotes
To discern the evolutionary pressures that select for epigenetic switches, we used computer simulations to evolve a mechanistic, biophysical model of a self-activating genetic circuit, which can both adapt genetically and exhibit epigenetic switching
Summary
Classic models of genetic adaptation presume that random genetic mutations generate novel phenotypes that can be selected by the environment [1]. E.g. small populations or fast fluctuating environments, the spontaneous appearance of a beneficial mutation might be too infrequent and, some organisms may induce genetic variation to accelerate adaptation to a new environment. Examples include adaptive mutation, where genetic variation occurs in response to the environment [2], directed mutation, where non-random and useful mutations are induced [3], and cryptic variation, where non-neutral mutations accumulate and are buffered without phenotypic consequences until the environment changes [4]. Many organisms have evolved biochemical networks that directly sense environmental cues and induce phenotypic responses to the new environment (known as “phenotypic plasticity”). The frequency of environmental change, the accuracy of cues, the penalty of non-adaptation, as well as the cost of producing the sensing machinery will determine the advantage of phenotypic plasticity [5, 6]
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