Global epistasis on fitness landscapes

TL;DR

This paper reviews how global epistasis patterns, where mutation effects depend on genetic background fitness, can aid in understanding and reconstructing complex fitness landscapes, despite the complexity introduced by mutation interactions.

Contribution

It provides an overview of recent work on global epistasis, explaining its emergence through geometric and mathematical reasoning, and discusses its implications for evolutionary predictions.

Findings

Global epistasis patterns can be predicted by geometric and mathematical models.

Different mutations exhibit varying global epistasis patterns, from diminishing to increasing returns.

Understanding global epistasis can improve fitness landscape reconstruction.

Abstract

Epistatic interactions between mutations add substantial complexity to adaptive landscapes, and are often thought of as detrimental to our ability to predict evolution. Yet, patterns of global epistasis, in which the fitness effect of a mutation is well-predicted by the fitness of its genetic background, may actually be of help in our efforts to reconstruct fitness landscapes and infer adaptive trajectories. Microscopic interactions between mutations, or inherent nonlinearities in the fitness landscape, may cause global epistasis patterns to emerge. In this brief review, we provide a succinct overview of recent work about global epistasis, with an emphasis on building intuition about why it is often observed. To this end, we reconcile simple geometric reasoning with recent mathematical analyses, using these to explain why different mutations in an empirical landscape may exhibit different global epistasis patterns - ranging from diminishing to increasing returns. Finally, we highlight open questions and research directions.