Skip to Main content Skip to Navigation
Theses

Évolution in silico des protéines monomériques et dimériques.

Abstract : The in silico evolution simulation of protein- or tRNAs-encoding genes has recently been paid much attention because it offers the possibility to deduce from simple assumptions striking and unexpected behaviours deriving from the genotype structure in sequence space and the genotype-phenotype mapping. The most elementary evolutionary model, known as the 'neutral theory of molecular evolution' developed and advocated by Kimura from the late 60s on, has given rise to a now well documented phenomenon: genotypes that are robust to mutations and encode fast-folding proteins as evidenced and measured by the folding temperature, turn out to be overrepresented as compared to fragile ones. Many questions still remain unsettled, amongst which whether a realistic model of functionality could change the picture drawn from models mainly based on structure preservation and/or foldability. We have therefore developed a model including a selective constraint imposing that the proteins encoded by two genes must specifically and efficiently dimerise in order to make an individual survive. We shall demonstrate that the neutral networks built upon structural considerations are plastic enough to accommodate the functional requirement without any noticeable impact on stability. The overrepresentation of robust genotypes still holds and appears to be magnified by the epistatic interactions between genes. Is is of interest that such a phenomenon is as well accompanied by an improvement in average functionality resulting from a functional superfunnel organisation in sequence space. This conclusion could have important implications in the way to explain the emergence of new functions. Another issue regards the simplifications involved by the proteins models. Simulations of evolution entail large computations, that have been tackled using lattice protein models. In this dissertation we propose an off-lattice protein model exhibiting more complex contact maps--which supports the conclusions drawn from the lattice model.
Document type :
Theses
Complete list of metadatas

https://pastel.archives-ouvertes.fr/pastel-00002261
Contributor : Ecole Polytechnique <>
Submitted on : Thursday, July 29, 2010 - 2:55:29 PM
Last modification on : Tuesday, October 20, 2020 - 10:51:10 AM
Long-term archiving on: : Tuesday, October 23, 2012 - 11:50:17 AM

Identifiers

  • HAL Id : pastel-00002261, version 1

Collections

Citation

Josselin Noirel. Évolution in silico des protéines monomériques et dimériques.. Biochimie, Biologie Moléculaire. Ecole Polytechnique X, 2006. Français. ⟨pastel-00002261⟩

Share

Metrics

Record views

424

Files downloads

379