title: Wiring for independence: positive feedback motifs facilitate individuation of traits in development and evolution.
abstract: Independent selection response of a trait is contingent on the availability of genetic variation that is not entangled with other traits. Mechanistically, such variational individuation in spite of shared genome results from gene regulation. Changes that increase individuation of traits are likely caused by gene regulatory changes. Yet the effect of regulatory evolution on population variation is understudied. Trait individuation also occurs during development. Developmental differentiation involves two stages-induction of differentiation and the maintenance of differentiated fate. The corresponding gene regulatory transition involves the feed-forward and the regulated feedback motifs. Here we consider analogous transition pattern at the evolutionary scale, establishing an autonomous regulatory sub-network involved in the independent trait variation. A population genetic simulation of regulated feedback loop dynamics under small perturbations shows a decoupling of variation in gene expression between the upstream gene and the responding downstream gene. We furthermore observe that the ranges of dynamics that can be generated by feedback and feed-forward networks overlap. Such phenotypic overlap enables genetic accessibility of network-specific expression dynamics. We suggest that feedback topology may eventually confer selective advantage leading from a gradual process to threshold individuation, i.e., the emergence of a novel trait.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Perinatal Institute, Cincinnati, Ohio.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Pavličev
authors.forename: Stefanie
authors.initials: S
authors.lastname: Widder
mesh_terms: D000818:Animals; D005075:Biological Evolution; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D048788:Growth and Development / Q000235:genetics*; D008954:Models, Biological; D010641:Phenotype; D040641:Quantitative Trait Loci