The Impact of Mistranslation on Phenotypic Variability and Fitness

Abstract

Phenotypic variation is widespread in natural populations, and can significantly alter their ecology and evolution. Phenotypic variation often reflects underlying genetic variation, but also manifests via non-heritable mechanisms. For instance, translation errors result in about 10% of cellular proteins carrying altered sequences. Thus, proteome diversification arising from translation errors can potentially generate phenotypic variability, in turn increasing variability in the fate of cells or of populations. However, this link remains unverified. We manipulated mistranslation levels in Escherichia coli, and measured phenotypic variability between single cells (individual level variation), as well as replicate populations (population level variation). Monitoring growth and survival, we find that mistranslation indeed increases variation across E. coli cells, but does not consistently increase variability in growth parameters across replicate populations. Interestingly, although any deviation from the wild type (WT) level of mistranslation reduces fitness in an optimal environment, the increased variation is associated with a survival benefit under stress. Hence, we suggest that mistranslation-induced phenotypic variation can impact growth and survival and has the potential to alter evolutionary trajectories.

The Boggarts of biology: how non-genetic changes influence the genotype

“…While phenotypic heterogeneity arising from increased variance in gene expression levels can seemingly contribute to adaptation under stress (Carey et al 2018), it also extracts a cost during normal conditions (Bodi et al 2017), creating a trade-off. Recently, we found that mistranslating E. coli cells show greater variability than the WT in cell size and division time (Samhita et al 2020b). Again, this is correlated with higher survival under some stresses.…”

Not quite lost in translation: Mistranslation alters adaptive landscape topography and the dynamics of evolution

“…This advantage comes at the cost of decreasing the fixation probability of many other beneficial mutations. However, considering experimental studies that demonstrate the fitness benefits of mistranslation in populations under stress (Javid et al, 2014;Mohler and Ibba, 2017;Ribas de Pouplana et al, 2014;Samhita et al, 2021) we suggest that mistranslation may often help the fixation of beneficial mutations in nature. We also found that mistranslation renders a small fraction of beneficial mutations deleterious, or vice versa (roughly 2 percent both ways).…”

“…These advantages are small in part because the mistranslation rates we used in our study come from a population of E. coli growing in a favourable environment (Mordret et al, 2019). However, mistranslation rates increase in stressful conditons (Netzer et al, 2009), and consequently the benefits we report here may be larger in nature (Samhita et al, 2021).…”

“…Third, mistranslation can affect the course of adaptation. Even though it detrimentally impacts cell physiology and fitness (Bratulic et al, 2017; Javid et al, 2014; Ribas de Pouplana et al, 2014; Samhita et al, 2021), mistranslation can be beneficial for adaptation. For example, higher rates of mistranslation increase resistance to the antibiotic rifampicin in mycobacteria (Javid et al, 2014).…”