Evolutionary System Biology

Challenge 5.Evolution is a complex, multilevel process that operates at long time scales and can only be understood from a systems perspective. Though we have a considerable wealth of experimental data, the major challenge is to develop models and theoretical frameworks to understand empirical results and to pose better focused experimental questions. One of the first unsolved questions is how phenotypes arise from genotypes. The full picture is lacking, and modelling is limited to the dynamics of molecules, for instance RNA or protein folding, or to the emergence of simple molecular interactions —as regulatory motifs. A deeper understanding of the structure of genotype spaces might lead, among others, to a quantification of the relative roles played by neutral and adaptive mechanisms. This research program will have to investigate the effects of evolutionary innovation. Can complex biological functions be constructed from previous simpler modules? How do regulatory circuits emerge? What are the limits to the design of robust and portable functional modules? Answers to these questions will assess the validity of reductionist approaches, as opposed to viewing innovation as an emergent phenomenon, arising from network-like distributed properties. In a broader framework, we should be concerned about the mechanistic origin of evolutionary transitions, and on the role played by external forcing versus contingent or stochastic phenomena in their generation. Evolution itself can be viewed as a tool for Synthetic Biology, since directed evolutionary selection is a way to attain desired functions. A major goal is to integrate design with a selection-driven exploration of phenotypic spaces. Advances will be conditional on the construction of large evolutionary platforms where experimental evolution informed by design and theory can proceed en masse. The exploration of the possible phenotypes of engineered organisms at a large scale, as opposed to simple addition or deletion of a gene, calls for an urgent understanding of the plasticity and adaptability of new organisms and their traits of interest. An eventual commercial use of these organisms demands more research at the frontiers between evolutionary science, climate, and ecology: how will the ecosystem be affected by these organisms, but also, how will the organisms be affected by the ecosystem in a rapidly changing environment?Peer reviewe