Analytical Descriptions of Fundamental Constraints in Protein Synthesis and Microbial Growth

The search for fundamental principles underlying cellular growth has long been a goal of microbiology. Recent years have yielded theoretical and experimental support for a candidate principle: growth in nutrient replete conditions is limited by protein synthesis and determined by how ribosomes are allocated towards making different protein classes. We introduce a low-dimensional model which investigates this principle, generating novel analytical expressions that define key properties of microbial growth (e.g.  translation rate and ribosome content) and explore how they depend on major physiological parameters (e.g. maximal translation rate and metabolic output). We then quantitatively explore strategies cells may employ for establishing specific growth rates where ribosomal content is either fixed across conditions, tuned to maintain fast translation, or tuned to optimize growth rate given the metabolic output. We compare our predictions to measurements of ribosome content and average translation rates for both E. coli and S. cerevisiae.  Despite their evolutionary distance, they share the same strategy for sculpting their proteome; ribosome synthesis is tuned to promote fast growth at the expense of the average translation rate. The agreement between theory and experiment illustrates that fundamental biological principles are encoded in this model. We discuss how this is achieved in E. coli and comment on how these findings relate to the eco-evolutionary histories of these organisms.