Bringing chance back into biological processes: Dissecting stochasticity in the timing of translation
Résumé
Chance in gene expression is typically addressed as “noise” in the context of transcription. By contrast, since translation is usually seen as “a linear conversion with one predictable, unambiguous outcome” (Putois et al 2015), its relation with stochasticity is seldom addressed. I have already explored the role of chance in transcription (Casali and Merlin 2020) arguing that it can be more than just noise, i.e. chance is an epistemic element having a specific role in biological explanations. In my presentation, I want to extend this kind of analysis to translation. Since transcription and translation processes happen in similar physico-chemical conditions, there is no a priori reason, theoretically speaking, that stochasticity would not affect this other stage of gene expression. This finds empirical confirmation in recent experimental research that clearly shows the pervasive influence of stochasticity on translation (e.g., Boersma et al 2019). Furthermore, in situations of cellular stress, translation privileges the synthesis of alternative proteins rather than standard ones (Sriram et al 2018). This event, called alternative start-codon selection, has recently been qualified as stochastic (Boersma et al 2019). Alternative proteins synthetized by chance are often seen as “error[s] in translation” (Boersma et al 2019, p. 459) or “translational noise” (Pauli et al 2015, p. 6). By contrast, I will ask whether the production of alternative proteins could be considered as a sort of bet-hedging strategy enacted by cells in order to face environmental stresses. If, following Orr et al (2020), these proteins can have a role in tumor prevention and in the maintenance of cellular homeostasis, then it seems they are essential for cell integrity. If so, we should re-examine intracellular processes at their origin from this perspective, and in particular re-evaluate the possible explanatory role of their stochastic character.