Final Report Summary - EVOSYSBIO (Systems biology meets evolutionary theory: modeling the genetics and adaptation of complex traits)
Limits to our understanding of the molecular basis of complex phenotypic traits present a major obstacle to the application of insights from the molecular life sciences in, for example, medicine and agrifood. Already simple small-scale biomolecular interaction networks, for which a detailed reconstruction of the genotype-phenotype relationship is still computationally feasible, serve to illustrate this fundamental problem. We demonstrated this by investigating networks responsible for chemotaxis, central carbon metabolism, starvation resistance and competence induction in bacteria, which all share the property that their biological function is an emergent outcome of interactions rather than a sum of effects contributed by individual genes (i.e. the current default model of trait architecture). We show, by means of computational work and evolution experiments, that the resulting complex mapping between genotype and phenotype produces highly heterogeneous adaptive landscapes with multiple fitness peaks that correspond to similar phenotypic but divergent molecular adaptations. Conversely, we illustrate that biochemical conservation principles at the molecular level are responsible for constraints and trade-offs observable at the phenotypic level (e.g. between chemotactic efficiency and the cost of operating the signal transduction network). Insights from this project motivate a mechanistic and integrated approach to studying adaptation in living systems, in which both biological function and molecular organisation are taken into account. When applied to higher organisms with sexual reproduction, this method provides new insights into several long-standing issues in evolutionary biology, including the evolution of cooperation, antagonistic coevolution, ageing, adaptive diversification and the genetic basis of phenotypic heterogeneity.