Epigenetic switching as a strategy for quick adaptation while attenuating biochemical noise

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.

The Molecular Mechanisms of Adaptive Response Related to Environmental Stress

“…Adaptation, defined as the ability “to adapt to a new situation with the aim to increase the chance or quality of surviving”, uses two basic strategies [ 35 ].…”

Epigenetic inheritance mediates phenotypic diversity in natural populations

“…Epigenetic information, which can be encoded independently of the DNA sequence, is essential for cell fate determination, development, and environmental responses in eukaryotes (Birnbaum and Roudier, 2017; Elsherbiny and Dobreva, 2021; Greenberg and Bourc’his, 2019; Zhang et al, 2018). In theory, if stably heritable and independent of DNA sequence polymorphism, epigenetic variation could influence inherited traits and contribute to adaptation (Gómez-Schiavon and Buchler, 2019; Kronholm and Collins, 2016; Slatkin, 2009). Epiallelic variation in several angiosperm genes, including Linaria vulgaris Cyc , tomato CNR and VTE3 , maize Spm , rice D1 , oil palm MANTLED , and Arabidopsis thaliana FWA, PAI2 and IAA7 , influences phenotypic outcomes (Quadrana and Colot, 2016; Shahzad et al, 2020).…”

Gene expression noise can promote the fixation of beneficial mutations in fluctuating environments

“…Bet-hedging strategies are widespread in nature, especially among bacteria [9], but are not the focus of this study. Another exception is a theoretical study [21] predicting that in periodically fluctuating environments, genotypes underlying increased nongenetic variation can also be more sensitive to mutation, a property that may increase evolvability [22]. Another study [23] found that phenotypic plasticity, which can bring forth nongenetic variation, can protect a population against extinction when the environment suddenly changes or when it fluctuates randomly.…”