A Whole Cell Model of Mycoplasma Genitalium Elucidates Mechanisms of Bacterial Replication

Abstract

A central challenge of biology is to understand how complex phenotypes are controlled by individual molecules and their interactions. We report the first computational model which explains the life cycle of an entire organism, Mycoplasma genitalium, including metabolism, macromolecule synthesis, and cytokinesis, from the chemical interactions of molecules. The model consists of submodels of 28 cellular processes integrated through 16 cellular states and accounts for every annotated gene function. Using the model we identified the molecular determinates of cellular replication. We found the M. genitalium cell cycle is 9.0 ± 0.5 h, and that most of its variance is due metabolism and thymidylate kinase expression. Additionally, we found that replication initiation and DnaA dynamics are a significant source of cell cycle variation among fast growing cells. We examined the genetic requirements of growth and found four distinct classes of single-gene deletion strains: wild-type indistinguishable, early growth cessation, slow growth decay, and non-dividing. The model correctly predicts the observed essentially of > 80% of genes. Gene-complete models will accelerate biomedical discovery and bioengineering by enabling rapid in silico experimentation, facilitating experimental design and interpretation, and guiding bioengineering and medicine.View Large Image | View Hi-Res Image | Download PowerPoint Slide