title: Environmental dependence of genetic constraint.
abstract: The epistatic interactions that underlie evolutionary constraint have mainly been studied for constant external conditions. However, environmental changes may modulate epistasis and hence affect genetic constraints. Here we investigate genetic constraints in the adaptive evolution of a novel regulatory function in variable environments, using the lac repressor, LacI, as a model system. We have systematically reconstructed mutational trajectories from wild type LacI to three different variants that each exhibit an inverse response to the inducing ligand IPTG, and analyzed the higher-order interactions between genetic and environmental changes. We find epistasis to depend strongly on the environment. As a result, mutational steps essential to inversion but inaccessible by positive selection in one environment, become accessible in another. We present a graphical method to analyze the observed complex higher-order interactions between multiple mutations and environmental change, and show how the interactions can be explained by a combination of mutational effects on allostery and thermodynamic stability. This dependency of genetic constraint on the environment should fundamentally affect evolutionary dynamics and affects the interpretation of phylogenetic data.
authors.affiliation: FOM Institute AMOLF, Amsterdam, the Netherlands.
authors.forename: Marjon G J
authors.initials: MG
authors.lastname: de Vos
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Poelwijk
authors.forename: Nico
authors.initials: N
authors.lastname: Battich
authors.forename: Joseph D T
authors.initials: JD
authors.lastname: Ndika
authors.forename: Sander J
authors.initials: SJ
authors.lastname: Tans
mesh_terms: D004843:Epistasis, Genetic; D048168:Escherichia coli K12 / Q000235:genetics* / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D059647:Gene-Environment Interaction; D056968:Lac Repressors / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D010802:Phylogeny; D013816:Thermodynamics
chemical_list: D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli