Abstract
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.
Highlights
Quantitative microbial physiology is marked by close interactions between experiment and modeling since its birth in the mid twentieth century
The Independent Double Adder (IDA) and Replication Double Adder (RDA) models have high scores, we found that many other combinations have higher I-values, including combinations that do not correspond to any meaningful model of the cell cycle (Figure 3 bottom)
Provided that once again proteins are partitioned at division, Eqs. (2) and (4) result in a fixed added volume per origin of replication between consecutive initiation events, the initiation-to-initiation adder δii
Summary
Quantitative microbial physiology is marked by close interactions between experiment and modeling since its birth in the mid twentieth century (see Jun et al, 2018 for a review of the history with extensive literature). Re-emerged from the new singlecell data is the adder principle (Campos et al, 2014; Jun and Taheri-Araghi, 2015; Taheri-Araghi et al, 2015), which states that individual cells grow by adding a fixed size from birth to division, Quantitative Examination of Bacterial Cell-Cycle Models independently from their size at birth. This principle has characteristic repercussions on cell size homeostasis. Several models have been proposed so far (Campos et al, 2014; IyerBiswas et al, 2014; Taheri-Araghi et al, 2015; Harris and Theriot, 2016; Wallden et al, 2016; Amir, 2017; Micali et al, 2018; Si et al, 2019; Witz et al, 2019; Bertaux et al, 2020; Serbanescu et al, 2020; Zheng et al, 2020), and we expect a consensus to emerge as more experimental data become available
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