title: toyLIFE: a computational framework to study the multi-level organisation of the genotype-phenotype map.
abstract: The genotype-phenotype map is an essential object to understand organismal complexity and adaptability. However, its experimental characterisation is a daunting task. Thus, simple models have been proposed and investigated. They have revealed that genotypes differ in their robustness to mutations; phenotypes are represented by a broadly varying number of genotypes, and simple point mutations suffice to navigate the space of genotypes while maintaining a phenotype. Nonetheless, most current models focus only on one level of the map (folded molecules, gene regulatory networks, or networks of metabolic reactions), so that many relevant questions cannot be addressed. Here we introduce toyLIFE, a multi-level model for the genotype-phenotype map based on simple genomes and interaction rules from which a complex behaviour at upper levels emerges -remarkably plastic gene regulatory networks and metabolism. toyLIFE is a tool that permits the investigation of how different levels are coupled, in particular how and where mutations affect phenotype or how the presence of certain metabolites determines the dynamics of toyLIFE gene regulatory networks. The model can easily incorporate evolution through more complex mutations, recombination, or gene duplication and deletion, thus opening an avenue to explore extended genotype-phenotype maps.
authors.affiliation: 1] Grupo Interdisciplinar de Sistemas Complejos (GISC), Madrid, Spain [2] Dept. Matemáticas, Universidad Carlos III de Madrid, Leganés, Madrid, Spain.
authors.forename: Clemente F
authors.initials: CF
authors.lastname: Arias
authors.affiliation: 1] Grupo Interdisciplinar de Sistemas Complejos (GISC), Madrid, Spain [2] Dept. Matemáticas, Universidad Carlos III de Madrid, Leganés, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Catalán
authors.affiliation: 1] Grupo Interdisciplinar de Sistemas Complejos (GISC), Madrid, Spain [2] Centro Nacional de Biotecnología (CSIC), Campus de Cantoblanco, Madrid, Spain.
authors.forename: Susanna
authors.initials: S
authors.lastname: Manrubia
authors.affiliation: 1] Grupo Interdisciplinar de Sistemas Complejos (GISC), Madrid, Spain [2] Dept. Matemáticas, Universidad Carlos III de Madrid, Leganés, Madrid, Spain [3] Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Cuesta
mesh_terms: D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks / Q000235:genetics*; D005838:Genotype; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype