Environmental Selection and Epistasis in an Empirical Phenotype-environment-fitness Landscape

Overview

Journal Nat Ecol Evol

Publisher Springer Nature

Specialty Biology

Date 2022 Feb 25

PMID 35210579

Authors

J Z Chen

D M Fowler

N Tokuriki

Affiliations

Soon will be listed here.

Abstract

Fitness landscapes, mappings of genotype/phenotype to their effects on fitness, are invaluable concepts in evolutionary biochemistry. Although widely discussed, measurements of phenotype-fitness landscapes in proteins remain scarce. Here, we quantify all single mutational effects on fitness and phenotype (EC) of VIM-2 β-lactamase across a 64-fold range of ampicillin concentrations. We then construct a phenotype-fitness landscape that takes variations in environmental selection pressure into account. We found that a simple, empirical landscape accurately models the ~39,000 mutational data points, suggesting that the evolution of VIM-2 can be predicted on the basis of the selection environment. Our landscape provides new quantitative knowledge on the evolution of the β-lactamases and proteins in general, particularly their evolutionary dynamics under subinhibitory antibiotic concentrations, as well as the mechanisms and environmental dependence of non-specific epistasis.

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