Multiscale digital Arabidopsis predicts individual organ and whole-organism growth

Understanding how dynamic molecular networks affect whole-organism physiology, analogous to mapping genotype to phenotype, remains a key challenge in biology. Quantitative models that represent processes at multiple scales and link understanding from several research domains can help to tackle this problem. Such integrated models are more common in crop science and ecophysiology than in the research communities that elucidate molecular networks. Several laboratories have modeled particular aspects of growth in Arabidopsis thaliana , but it was unclear whether these existing models could productively be combined. We test this approach by constructing a multiscale model of Arabidopsis rosette growth. Four existing models were integrated with minimal parameter modification (leaf water content and one flowering parameter used measured data). The resulting framework model links genetic regulation and biochemical dynamics to events at the organ and whole-plant levels, helping to understand the combined effects of endogenous and environmental regulators on Arabidopsis growth. The framework model was validated and tested with metabolic, physiological, and biomass data from two laboratories, for five photoperiods, three accessions, and a transgenic line, highlighting the plasticity of plant growth strategies. The model was extended to include stochastic development. Model simulations gave insight into the developmental control of leaf production and provided a quantitative explanation for the pleiotropic developmental phenotype caused by overexpression of miR156, which was an open question. Modular, multiscale models, assembling knowledge from systems biology to ecophysiology, will help to understand and to engineer plant behavior from the genome to the field. Significance Plants respond to environmental change by triggering biochemical and developmental networks across multiple scales. Multiscale models that link genetic input to the whole-plant scale and beyond might therefore improve biological understanding and yield prediction. We report a modular approach to build such models, validated by a framework model of Arabidopsis thaliana comprising four existing mathematical models. Our model brings together gene dynamics, carbon partitioning, organ growth, shoot architecture, and development in response to environmental signals. It predicted the biomass of each leaf in independent data, demonstrated flexible control of photosynthesis across photoperiods, and predic