Stochasticity versus determinism: consequences for realistic gene regulatory network modelling and evolution.
Gene regulation is one important mechanism in producing observed phenotypes and heterogeneity. Consequently, the study of gene regulatory network (GRN) architecture, function and evolution now forms a major part of modern biology. However, it is impossible to experimentally observe the evolution of GRNs on the timescales on which living species evolve. In silico evolution provides an approach to studying the long-term evolution of GRNs, but many models have either considered network architecture from non-adaptive evolution, or evolution to non-biological objectives. Here, we address a number of important modelling and biological questions about the evolution of GRNs to the realistic goal of biomass production. Can different commonly used simulation paradigms, in particular deterministic and stochastic Boolean networks, with and without basal gene expression, be used to compare adaptive with non-adaptive evolution of GRNs? Are these paradigms together with this goal sufficient to generate a range of solutions? Will the interaction between a biological goal and evolutionary dynamics produce trade-offs between growth and mutational robustness? We show that stochastic basal gene expression forces shrinkage of genomes due to energetic constraints and is a prerequisite for some solutions. In systems that are able to evolve rates of basal expression, two optima, one with and one without basal expression, are observed. Simulation paradigms without basal expression generate bloated networks with non-functional elements. Further, a range of functional solutions was observed under identical conditions only in stochastic networks. Moreover, there are trade-offs between efficiency and yield, indicating an inherent intertwining of fitness and evolutionary dynamics.
Jenkins
Dafyd J
DJ
Centre for Systems Biology, School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. dafyd.jenkins@warwick.ac.uk
Stekel
Dov J
DJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D009154:Mutation; D009696:Nucleic Acids / Q000378:metabolism; D013269:Stochastic Processes
D009696:Nucleic Acids; D000255:Adenosine Triphosphate