Epistasis and Shapes of Fitness Landscapes

TL;DR

This paper introduces a geometric framework using genotopes and triangulations to analyze the shapes of fitness landscapes and uncover complex gene interactions across multiple loci.

Contribution

It develops a novel geometric theory linking fitness landscape shapes to gene interactions, extending analysis beyond two-locus cases.

Findings

Refined gene interaction analysis in HIV fitness data.

Detected previously unknown gene interactions in Drosophila.

Provided a comprehensive geometric approach to fitness landscape analysis.

Abstract

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 possible allele frequencies in populations. Triangulations of the genotope correspond to different shapes of fitness landscapes and reveal all the gene interactions. The theory is applied to fitness data from HIV and Drosophila melanogaster. In both cases, our findings refine earlier analyses and reveal previously undetected gene interactions.