Learning the pattern of epistasis linking genotype and phenotype in a protein.

ABSTRACT: Understanding the pattern of epistasis-the non-independence of mutations-is critical for relating genotype and phenotype. However, the combinatorial complexity of potential epistatic interactions has severely limited the analysis of this problem. Using new mutational approaches, we report a comprehensive experimental study of all 2¹³ mutants that link two phenotypically distinct variants of the Entacmaea quadricolor fluorescent protein-an opportunity to examine epistasis up to the 13^th order. The data show the existence of many high-order epistatic interactions between mutations, but also reveal extraordinary sparsity, enabling novel experimental and computational strategies for learning the relevant epistasis. We demonstrate that such information, in turn, can be use

SUBMITTER: Poelwijk FJ 

PROVIDER: S-EPMC6746860 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature