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Communication Dans Un Congrès Année : 2021

Dissecting stochasticity in gene expression: new epistemological insights by a multidimensional analysis

Résumé

Since the 1990s, researches dealing with stochasticity in molecular and cellular biology have been mainly focused on the process of gene expression, especially on transcription. In this context, stochasticity is conceived as noise, and is defined and measured as random variation around the mean value of a given gene expression parameter (i.e., the concentration/number of RNAs or proteins produced; see Elowitz 2002). The focus here is thus on what we call “quantitative stochasticity” (QTS), i.e., stochastic processes whose effects influence the amount of genetic products synthetized from the same DNA sequence (e.g., Pilpel 2011). More and more research studies suggest that QTS in transcription is not just mere noise (i.e., a perturbation or error with respect to some expected result), but can be a relevant parameter likely to play a role in the explanation of cell differentiation and development (cf. Casali & Merlin 2020). What about stochasticity in translation? This other step of gene expression, and stochasticity affecting it, have seldom been studied. Recent experimental researches clearly show the pervasive influence of stochasticity on translation too, in particular on the type of protein(s) produced (e.g., Boersma et al 2019). We talk about “qualitative stochasticity” (QLS) to refer to stochastic processes whose effects influence the diversity (type) of genetic products synthetized from the same DNA sequence. By focusing on a case of “noncanonical translational events”, namely alternative start-codon selection events, we argue that QLS in translation is not mere noise but can make a difference in gene expression, and further in cell differentiation and development. Thus, it can have an explanatory role to account for these processes. Our argument relies on the distinction of various dimensions where stochasticity takes place: two temporal dimensions (time as order and time as duration), and two spatial dimensions (homogeneous and heterogeneous intracellular space), coupled with considerations based on the law of large numbers. Taking into account all these dimensions, we argue, allow for a better evaluation and understanding of the ways QLS affects translation dynamics, and its very role in the explanation of gene expression results.
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Dates et versions

hal-04019284 , version 1 (08-03-2023)

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  • HAL Id : hal-04019284 , version 1

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Marco Casali. Dissecting stochasticity in gene expression: new epistemological insights by a multidimensional analysis. The International Society for the History, Philosophy and Social Studies of Biology (ISHPSSB) 2021, Cold Spring Harbor Laboratory (CSHL), Jul 2021, Online, France. ⟨hal-04019284⟩
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