Quantitative examination of five stochastic cell-cycle and cell-size control models forEscherichia coliandBacillus subtilis

We examine five quantitative models of the cell-cycle and cell-size control in Escherichia coli and Bacillus subtilis that have been proposed over the last decade to explain single-cell experimental data generated with high-throughput methods. After presenting the statistical properties of these models, we test their predictions against experimental data. Based on simple calculations of the defining correlations in each model, we first dismiss the stochastic Helmstetter-Cooper model and the Initiation Adder model, and show that both the Replication Double Adder and the Independent Double Adder model are more consistent with the data than the other models. We then apply a recently proposed statistical analysis method and obtain that the Independent Double Adder model is the most likely model of the cell cycle. By showing that the Replication Double Adder model is fundamentally inconsistent with size convergence by the adder principle, we conclude that the Independent Double Adder model is most consistent with the data and the biology of bacterial cell-cycle and cell-size control. Mechanistically, the Independent Adder Model is equivalent to two biological principles: (i) balanced biosynthesis of the cell-cycle proteins, and (ii) their accumulation to a respective threshold number to trigger initiation and division.