Proteostasis Environment Shapes Higher-Order Epistasis Operating on Antibiotic Resistance

High-order epistasis shapes evolutionary trajectories

High-order epistasis-where the effect of a mutation is determined by interactions with two or more other mutations-makes small, but detectable, contributions to genotype-fitness maps. While epistasis between pairs of mutations is known to be an important determinant of evolutionary trajectories, the evolutionary consequences of high-order epistasis remain poorly understood. To determine the eff...

Identifying the importance of higher order epistasis

Higher order epistasis and fitness peaks

We show that higher order epistasis has a substantial impact on evolutionary dynamics by analyzing peaks in the fitness landscapes. There are 193,270,310 fitness graphs, or cube orientations, for 4-locus systems, distributed on 511, 863 isomorphism classes. We identify all fitness graphs with 6 or more peaks. 81 percent of them imply 4-way epistasis, whereas 9 percent of all 4-locus fitness gra...

Epistasis and Shapes of Fitness Landscapes

The relationship between the shape of a fitness landscape and the underlying gene interactions, or epistasis, has been extensively studied in the two-locus case. Gene interactions among multiple loci are usually reduced to two-way interactions. We present a geometric theory of shapes of fitness landscapes for multiple loci. A central concept is the genotope, which is the convex hull of all poss...

Modeling Shapes with Higher-Order Graphs: Methodology and Applications

Extrinsic factors such as object pose and camera parameters are a main source of shape variability and pose an obstacle to efficiently solving shape matching and inference. Most existing methods address the influence of extrinsic factors by decomposing the transformation of the source shape (model) into two parts: one corresponding to the extrinsic factors and the other accounting for intra-cla...