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Communication Dans Un Congrès Année : 2021

Dissecting chance in translation: from quantitative to qualitative stochasticity

Résumé

The majority of research into chance in molecular and cellular biology focuses on the concept of noise at the level of transcriptional processes (e.g. Elowitz et al 2002). Noise is often quantified in terms of random variation around the mean value of gene expression (i.e., the average number of RNAs or polypeptides produced; see Levine et al 2020). This kind of study is what we call quantitative stochasticity (QS). We define the study of QS as the study of stochastic processes, the effects of which influence the concentration (the numbers) of genetic products (e.g. see Pilpel 2011 and Salari et al 2012). In the presentation we stress that studies on stochasticity are mainly focused on QS in transcription. But what about stochasticity in translation? Since transcription and translation processes happen in similar biophysical conditions, theoretically speaking there exist no a priori reasons to prevent chance from influencing this stage of gene expression, either in a negative or in a positive way. This theoretical intuition finds empirical confirmation. The latest empirical evidence clearly shows the pervasive influence of stochasticity in translation (e.g. Boersma et al 2019). In addition, this evidence underlines how stochasticity can influence the type of polypeptides produced. We call this kind of stochasticity qualitative stochasticity (here after QLS). We define the study of QLS as the study of stochastic processes, the effects of which influence the diversity (type) of genetic products (i.e. the diversity of polypeptides sequences) which start from the same RNA sequence. More specifically, QLS involves having polypeptide sequences that differ not only in concentration (quantity) but mainly in type (quality). Nonetheless, the way in which the latest evidence describes chance shows that finding a definition for it is not always so easy. For example, there is a tendency to exclude stochasticity as a possible function of cell metabolism. But what is meant by “stochasticity” and “function” is seldom specified. Lexical meanings must be intuited or understood via tacit semantic agreement present within biological communities. But intuition and tacit agreement guarantee neither clearness nor universality. Indeed, since different scientific communities use different terminology, what could be intuitive and universal for one community might cause confusion for another. In taking the latest empirical evidence seriously, we aim to establish coherence and clarity. We propose focusing attention on time, a parameter often undervalued in biological descriptions. In our view, time is pivotal to properly understanding the meaning and role of QLS in translation. More specifically, in light of the complexity of translation processes, our strategy is to focus on a specific example, namely the alternative start-codon selection event as it appears particularly influenced by chance. We describe in detail the way in which the alternative start-codon selection event is modeled and highlight the lack of reference to time. By contrast, we argue in favor of a plurality of time models that can, in turn, highlight a variety of ways that stochasticity can act in alternative start-codon selection and, more generally, in translation.
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Dates et versions

hal-04021247 , version 1 (09-03-2023)

Identifiants

  • HAL Id : hal-04021247 , version 1

Citer

Marco Casali. Dissecting chance in translation: from quantitative to qualitative stochasticity. 8èmes journées « Complexité-Désordre », Université Paris Diderot, Oct 2021, Paris, France. ⟨hal-04021247⟩
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