Network Analysis of Protein Adaptation: Modeling the Functional Impact of Multiple Mutations.

ABSTRACT: The evolution of new biochemical activities frequently involves complex dependencies between mutations and rapid evolutionary radiation. Mutation co-occurrence and covariation have previously been used to identify compensating mutations that are the result of physical contacts and preserve protein function and fold. Here, we model pairwise functional dependencies and higher order interactions that enable evolution of new protein functions. We use a network model to find complex dependencies between mutations resulting from evolutionary trade-offs and pleiotropic effects. We present a method to construct these networks and to identify functionally interacting mutations in both extant and reconstructed ancestral sequences (Network Analysis of Protein Adaptation). The time ordering of mutatio

SUBMITTER: Beleva Guthrie V 

PROVIDER: S-EPMC5967520 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature