Why does a mutation have a deleterious effect when it occurs in one species but shows no apparent consequences on the phenotype when it occurs in another species? What are some of possible explanations on the molecular basis of this phenomenon? Are the computational predictions of the extent of this phenomenon in nature accurate? The present project aims to take a swing at answering, at least partially, these basic questions of epistasis in molecular evolution. Within our work we plan to address these issues using computational approaches, systematic fitness assays of engineered orthologous genotypes and experimental functional assays of specific cases of epistasis identified by evolutionary analysis. By tackling these goals and utilising this array of approaches the projects aims to create a synthesis between theory and experimentation under the confines of a single laboratory that will allow us to study this phenomenon in a systematic fashion on the interface of different fields and methodologies.
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