Quantitative Examination of Five Stochastic Cell-Cycle and Cell-Size Control Models for Escherichia coli and Bacillus 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 (RDA) and the Independent Double Adder (IDA) model are more consistent with the data than the other models. We then apply a recently proposed statistical analysis method and obtain that the IDA model is the most likely model of the cell cycle. By showing that the RDA model is fundamentally inconsistent with size convergence by the adder principle, we conclude that the IDA 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. ; © 2021 Le Treut, Si, Li and Jun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 07 June 2021; Accepted: 06 October 2021; Published: 26 October 2021. We thank Martin Howard, Sandeep Krishna, Vahid Shahrezaei, and members of Hwa and Jun labs at UCSD for critical feedback and discussions. This work was supported by National Science Foundation (MCB ...