How genotypes are manifested into phenotypes, known as fitness landscapes, remains one of the most important unanswered questions in biology. However, deep mutational scans - empirical assays of the fitness landscapes - are increasingly being used to shape our understanding of the complex nature of interaction of changes on the genetic level. In my talk I will outline what we have learned from our study of the empirical assays of different orthologues of the Green Fluorescent Protein. We find that the fitness peak associated with each orthologue is unique, demonstrating different overall shape but also showing interactions between different amino acid sites. We have also been able to utilize these data and make generalized models of the fitness landscapes that are fairly accurate at genetic distances vastly beyond what has been assayed experimentally. The uniqueness of the shape of each fitness peak, however, leads to an inherent limitation of predicting the shape of one fitness peak based on the information contained in another fitness peak. To create better and more general models of fitness landscapes different empirical and theoretical approaches will be needed.
Diversity of fitness peak shapes in the Green Fluorescent Protein