title: De novo evolution of complex, global and hierarchical gene regulatory mechanisms.
abstract: Gene regulatory networks exhibit complex, hierarchical features such as global regulation and network motifs. There is much debate about whether the evolutionary origins of such features are the results of adaptation, or the by-products of non-adaptive processes of DNA replication. The lack of availability of gene regulatory networks of ancestor species on evolutionary timescales makes this a particularly difficult problem to resolve. Digital organisms, however, can be used to provide a complete evolutionary record of lineages. We use a biologically realistic evolutionary model that includes gene expression, regulation, metabolism and biosynthesis, to investigate the evolution of complex function in gene regulatory networks. We discover that: (i) network architecture and complexity evolve in response to environmental complexity, (ii) global gene regulation is selected for in complex environments, (iii) complex, inter-connected, hierarchical structures evolve in stages, with energy regulation preceding stress responses, and stress responses preceding growth rate adaptations and (iv) robustness of evolved models to mutations depends on hierarchical level: energy regulation and stress responses tend not to be robust to mutations, whereas growth rate adaptations are more robust and non-lethal when mutated. These results highlight the adaptive and incremental evolution of complex biological networks, and the value and potential of studying realistic in silico evolutionary systems as a way of understanding living systems.
authors.affiliation: Centre for Systems Biology, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. Dafyd.jenkins@warwick.ac.uk
authors.forename: Dafyd J
authors.initials: DJ
authors.lastname: Jenkins
authors.forename: Dov J
authors.initials: DJ
authors.lastname: Stekel
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D008962:Models, Theoretical; D014176:Protein Biosynthesis / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000502:physiology; D013379:Substrate Specificity / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins