Comparative genomics is fundamental to guide experiments and provides tools for functional infor-mation transfer across genomes. Performing similar set of experiments on the same biological systemin different organisms, will enable the reconstruction of the corresponding networks of regulations.However, it is hard to imagine that we will be able to elucidate how the system evolved without adetailed understanding of its dynamical properties: evolution selects genetic circuits on the basis oftheir activity: in general, we may say that evolution selects a system’s arrangement on the basis ofthe input/output response with additional features also important, such as the robustness to changesin physical or biological conditions. Mathematical modelling of ”orthologous” biological systems indifferent organisms can provide information about how arrangement variations affect evolutionarymeaningful properties of the circuit, a mission that is almost impossible for static reconstructions.Modelling could for instance show how the often-redundant regulations of functionally important regulators affect the dynamic properties of the system. A natural question is how the different regulatoryschemes working in related species affect the dynamical properties of the system, to extrapolate im-portant evolutionary insights on the selective pressures that might have shaped the system. Are thealternative arrangements all similarly robust with respect to evolutionary or environmental variations?Can we understand which evolutionary changes are responsible for optimizing such robustness? Whatspecific property follows a particular arrangement? By integrating different sources of information intomeaningful mathematical models, we can study the dynamics of a system at a detail level impossibleto achieve through wet-lab experiments. That is, redundant, reduced or simply different regulations characterizing different organisms can be traced through experiment and comparative genomics, butunderstanding their effects on the properties of the system can best be achieved through dynamic models. While the study of a single model allows to understand its specific properties, it does notprovide understanding about the evolution of a system’s structure. We propose an approach that wecall Comparative Systems Biology, whose aim is to introduce evolutionary thinking in modelling approaches through the comparison of the reconstructions of “orthologous” systems in different species. Clearly we are working on many different issues, but this is where we would like to go!
(PDF) Manifest of the Comparative Systems Biology Unit. Available from: https://www.researchgate.net/publication/333748732_Manifest_of_the_Comparative_Systems_Biology_Unit [accessed Mar 13 2023].