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Random perturbation of nanoscale copying machines
Par Marco Ribezzi (ESPCI Paris)
Le 4 Octobre 2022 à 11h00 - Salle de séminaires 5ème étage, Tour 32-33


Statistical mechanics allows us to explain or predict how macroscopic, deterministic laws arise out of molecular chaos and has found applications in areas where emergent behaviors stem from the interaction of large numbers of individual entities. Here we use ideas from statistical mechanics to analyse the evolution of gene libraries subject to in-vitro Directed Evolution (DE), i.e. to mimicking evolution in the laboratory via cycles of mutation/recombination and selection. 

Using systematic perturbation theories based on linear (Fluctuation Dissipation Theorem) and non-linear (Fluctuation Relations) response theory, we measure single-point fitness effects from non-ideal gene populations. This approach leads to a considerable speed-up in the identification of gain-of-function mutations when applied to fully in-vitro DE experiments on variants of the DNA polymerase of the Phi29 bacteriophage of B. Subtilis.