title: Fisher's geometrical model emerges as a property of complex integrated phenotypic networks.
abstract: Models relating phenotype space to fitness (phenotype-fitness landscapes) have seen important developments recently. They can roughly be divided into mechanistic models (e.g., metabolic networks) and more heuristic models like Fisher's geometrical model. Each has its own drawbacks, but both yield testable predictions on how the context (genomic background or environment) affects the distribution of mutation effects on fitness and thus adaptation. Both have received some empirical validation. This article aims at bridging the gap between these approaches. A derivation of the Fisher model "from first principles" is proposed, where the basic assumptions emerge from a more general model, inspired by mechanistic networks. I start from a general phenotypic network relating unspecified phenotypic traits and fitness. A limited set of qualitative assumptions is then imposed, mostly corresponding to known features of phenotypic networks: a large set of traits is pleiotropically affected by mutations and determines a much smaller set of traits under optimizing selection. Otherwise, the model remains fairly general regarding the phenotypic processes involved or the distribution of mutation effects affecting the network. A statistical treatment and a local approximation close to a fitness optimum yield a landscape that is effectively the isotropic Fisher model or its extension with a single dominant phenotypic direction. The fit of the resulting alternative distributions is illustrated in an empirical data set. These results bear implications on the validity of Fisher's model's assumptions and on which features of mutation fitness effects may vary (or not) across genomic or environmental contexts.
authors.affiliation: ISE-M Institut des Sciences de l'Evolution, Unité Mixte de Recherche 5554-Centre National de la Recherche Scientifique-Université Montpellier 2, 34095 Montpellier Cedex 05, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Martin
mesh_terms: D019143:Evolution, Molecular; D056084:Genetic Fitness; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic
keywords: Fisher’s geometrical model; mutation fitness effects; network biology; random matrix theory; systems biology