A fundamental and theoretical framework for mutation interactions and epistasis

Abstract

Many pathological conditions are a result of intragenic epistasis; however, there are ambiguities in current epistasis models. Herein, the new Mutation Interaction Spectrum model defines a discrete outcome, named a Mutation Interaction, for each double point mutation in a gene and its component single mutations. The model is a universal genetic model of all types of mutation interactions and their functional outcomes and is derived from digital logic, commonly used in electrical engineering. Mutation interactions are normally classified as positive and negative epistasis. The model logics unifies common genetic relationships into one model, normalizing biological nomenclature, and disambiguates them with the 16 possible logic-based interactions. The model was tested by assaying transcriptional activity induced by HIV-1 Tat protein, for a random sampling of 3429 double mutations and all 1615 single mutations. All possible types of logic were observed for the Tat mutation interactions.