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Register a new userReplication initiation in E. coli is regulated via an origin-density sensor generating adder correlations
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All living cells need to coordinate DNA replication with growth and division to generate cell cycles that are stable in time. The bacterium Escherichia coli initiates replication at a volume per origin that on average is independent of the growth rate. It also adds an on average constant volume per origin between successive initiation events, independent of the initiation size. Yet, a molecular model that can explain these observations has been lacking. Here, we develop a mathematical model of DNA replication initiation in E. coli that is consistent with a wealth of experimental data. We first show that the previously proposed initiator titration model, which is based on the accumulation of the initiator protein DnaA on chromosomal titration sites, is not consistent with the experimental data. We then present a model that is based on an ultra-sensitive switch between an inactive form of DnaA and an active form that induces replication initiation. Our model shows that at low growth rates the switch is predominantly controlled by activation of DnaA via lipids and deactivation via the chromosomal site datA, while at high growth rates DARS2 and RIDA become essential. Crucially, in our mean-field model DNA replication is initiated at a constant volume per origin, qualifying our model as a sizer. Yet, we show that in a stochastic version of the same model the inevitable fluctuations in the components that control the DnaA activation switch naturally give rise to the experimentally observed adder correlations.
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Organisms must acquire and use environmental information to guide their behaviors. However, it is unclear whether and how information quantitatively limits behavioral performance. Here, we relate information to behavioral performance in Escherichia coli chemotaxis. First, we derive a theoretical limit for the maximum achievable gradient-climbing speed given a cells information acquisition rate. Next, we measure cells gradient-climbing speeds and the rate of information acquisition by the chemotaxis pathway. We find that E. coli make behavioral decisions with much less than the 1 bit required to determine whether they are swimming up-gradient. However, they use this information efficiently, performing near the theoretical limit. Thus, information can limit organisms performance, and sensory-motor pathways may have evolved to efficiently use information from the environment.
An important issue for the origins of life is how to ensure the accurate maintenance of information in replicating polymers in the face of inevitable errors. We investigate how this maintenance depends on reaction kinetics by incorporating elementary steps of polymerization into the population dynamics of polymers. We find that template-directed polymerization entails an inherent error-correction mechanism akin to kinetic proofreading, making a longer polymer more tolerant to an error catastrophe. Since this mechanism requires no enzyme, it is likely to operate under wide prebiotic conditions.
We propose a decoherence protected protocol for sending single photon quantum states through depolarizing channels. This protocol is implemented via an approximate quantum adder engineered through spontaneous parametric down converters, and shows higher success probability than distilled quantum teleportation protocols for distances below a threshold depending on the properties of the channel.
Cells have evolved a metabolic control of DNA replication to respond to a wide range of nutritional conditions. Accumulating data suggest that this poorly understood control depends, at least in part, on Central Carbon Metabolism (CCM). In Bacillus subtilis , the glycolytic pyruvate kinase (PykA) is intricately linked to replication. This 585 amino-acid-long enzyme comprises a catalytic (Cat) domain that binds to phosphoenolpyruvate (PEP) and ADP to produce pyruvate and ATP, and a C-terminal domain of unknown function. Interestingly, the C-terminal domain termed PEPut interacts with Cat and is homologous a domain that, in other metabolic enzymes, are phosphorylated at a conserved TSH motif at the expense of PEP and ATP to drive sugar import and catalytic or regulatory activities. To gain insights into the role of PykA in replication, DNA synthesis was analyzed in various Cat and PEPut mutants grown in a medium where the metabolic activity of PykA is dispensable for growth. Measurements of replication parameters ( ori/ter ratio, C period and fork speed) and of the pyruvate kinase activity showed that PykA mutants exhibit replication defects resulting from side chain modifications in the PykA protein rather than from a reduction of its metabolic activity. Interestingly, Cat and PEPut have distinct commitments in replication: while Cat impacts positively and negatively replication fork speed, PEPut stimulates initiation through a process depending on Cat-PEPut interaction and growth conditions. Residues binding to PEP and ADP in Cat, stabilizing the Cat-PEPut interaction and belonging to the TSH motif of PEPut were found important for the commitment of PykA in replication. In vitro , PykA affects the activities of replication enzymes (the polymerase DnaE, helicase DnaC and primase DnaG) essential for initiation and elongation and genetically linked to pykA . Our results thus connect replication initiation and elongation to CCM metabolites (PEP, ATP and ADP), critical Cat and PEPut residues and to multiple links between PykA and the replication enzymes DnaE, DnaC and DnaG. We propose that PykA is endowed with a moonlighting activity that senses the concentration of signaling metabolites and interacts with replication enzymes to convey information on the cellular metabolic state to the replication machinery and adjust replication initiation and elongation to metabolism. This defines a new type of replication regulator proposed to be part of the metabolic control that gates replication in the cell cycle.
Bacteria have remarkably robust cell shape control mechanisms. For example, cell diameter only varies by a few percent across a population. MreB is necessary for establishment and maintenance of rod shape although the mechanism of shape control remains unknown. We perturbed MreB in two complimentary ways to produce steady-state cell diameters over a wide range, from 790+/-30 nm to 1700+/-20 nm. To determine which properties of MreB are important for diameter control, we correlated structural characteristics of fluorescently-tagged MreB polymers with cell diameter by simultaneously analyzing 3-dimensional images of MreB and cell shape. Our results indicate that the pitch angle of MreB inversely correlates with cell diameter. Other correlations are not found to be significant. These results demonstrate that the physical properties of MreB filaments are important for shape control and support a model in which MreB dictates cell diameter and organizes cell wall growth to produce a chiral cell wall.
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