Selection biases the prevalence and type of epistasis along adaptive trajectories

TL;DR

This paper investigates how natural selection influences the structure and prevalence of epistasis during adaptation, revealing biases that change over time and affect interpretations of evolutionary dynamics.

Contribution

It introduces a mathematical framework showing how selection biases epistatic interactions throughout adaptation, with implications for interpreting experimental data.

Findings

Epistasis is less common early and more common later in adaptation.

The nature of epistasis shifts from antagonistic to synergistic over time.

Biases in mutation substitution depend on population size and other parameters.

Abstract

The contribution to an organism's phenotype from one genetic locus may depend upon the status of other loci. Such epistatic interactions among loci are now recognized as fundamental to shaping the process of adaptation in evolving populations. Although little is known about the structure of epistasis in most organisms, recent experiments with bacterial populations have concluded that antagonistic interactions abound and tend to de-accelerate the pace of adaptation over time. Here, we use a broad class of mathematical fitness landscapes to examine how natural selection biases the mutations that substitute during evolution based on their epistatic interactions. We find that, even when beneficial mutations are rare, these biases are strong and change substantially throughout the course of adaptation. In particular, epistasis is less prevalent than the neutral expectation early in adaptation and much more prevalent later, with a concomitant shift from predominantly antagonistic interactions early in adaptation to synergistic and sign epistasis later in adaptation. We observe the same patterns when re-analyzing data from a recent microbial evolution experiment. Since these biases depend on the population size and other parameters, they must be quantified before we can hope to use experimental data to infer an organism's underlying fitness landscape or to understand the role of epistasis in shaping its adaptation. In particular, we show that when the order of substitutions is not known to an experimentalist, then standard methods of analysis may suggest that epistasis retards adaptation when in fact it accelerates it.