Noise in a minimal regulatory network: plasmid copy number control

2001 ◽  
Vol 34 (1) ◽  
pp. 1-59 ◽  
Author(s):  
Johan Paulsson ◽  
Måns Ehrenberg
Keyword(s):  
Copy Number Variation ◽  
Rate Constants ◽  
Copy Number ◽  
Time Delays ◽  
Plasmid Copy Number ◽  
Plasmid Copy ◽  
Copy Number Control ◽  
Plasmid R1 ◽  
Number Variation ◽  
Control Curves

1. Introduction 22. Plasmid biology 32.1 What are plasmids? 32.2 Evolution of CNC: cost and benefit 42.3 Plasmids are semi-complete regulatory networks 62.4 The molecular mechanisms of CNC for plasmids ColE1 and R1 62.4.1 ColE1 72.4.2 R1 72.5 General simplifying assumptions and values of rate constants 93. Macroscopic analysis 113.1 Regulatory logic of inhibitor-dilution CNC 113.2 Sensitivity amplification 123.3 Plasmid control curves 133.4 Multistep control of plasmid ColE1: exponential control curves 143.5 Multistep control of plasmid R1: hyperbolic control curves 163.6 Time-delays, oscillations and critical damping 184. Mesoscopic analysis 204.1 The master equation approach 204.2 A random walker in a potential well 234.3 CNC as a stochastic process 244.4 Sensitivity amplification 264.4.1 Single-step hyperbolic control 264.4.2 ColE1 multistep control can eliminate plasmid copy number variation 284.4.3 Replication backup systems – the Rom protein of ColE1 and CopB of R1 294.5 Time-delays 304.5.1 Limited rate of inhibitor degradation 304.5.2 Precise delays – does unlimited sensitivity amplification always reduce plasmid losses? 324.6 Order and disorder in CNC 334.6.1 Disordered CNC 344.6.2 Ordered CNC: R1 multistep control gives narrowly distributed interreplication times 344.7 Noisy signalling – disorder and sensitivity amplification 374.7.1 Eliminating a fast but noisy variable 384.7.2 Conditional inhibitor distribution: Poisson 394.7.3 Increasing inhibitor variation I: transcription in bursts 404.7.4 Increasing inhibitor variation II: duplex formation 414.7.5 Exploiting fluctuations for sensitivity amplification: stochastic focusing 444.7.6 A kinetic uncertainty principle 454.7.7 Disorder and stochastic focusing 464.7.8 Do plasmids really use stochastic focusing? 474.8 Metabolic burdens and values of in vivo rate constants 485. Previous models of copy number control 495.1 General models of CNC 495.2 Modelling plasmid ColE1 CNC 495.3 Modelling plasmid R1 CNC 526. Summary and outlook: the plasmid paradigm 537. Acknowledgements 568. References 56This work is a theoretical analysis of random fluctuations and regulatory efficiency in genetic networks. As a model system we use inhibitor-dilution copy number control (CNC) of the bacterial plasmids ColE1 and R1. We chose these systems because they are simple and well-characterised but also because plasmids seem to be under an evolutionary pressure to reduce both average copy numbers and statistical copy number variation: internal noise.

scholarly journals Genomic Characterization and Copy Number Variation ofBacillus anthracisPlasmids pXO1 and pXO2 in a Historical Collection of 412 Strains

mSystems ◽  
2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Angela Pena-Gonzalez ◽  
Luis M. Rodriguez-R ◽  
Chung K. Marston ◽  
Jay E. Gee ◽  
Christopher A. Gulvik ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Bacillus Anthracis ◽  
Copy Number ◽  
Plasmid Copy Number ◽  
Mobile Elements ◽  
Gene Content ◽  
Large Collection ◽  
Plasmid Copy ◽  
Content Type ◽  
Number Variation

ABSTRACTBacillus anthracisplasmids pXO1 and pXO2 carry the main virulence factors responsible for anthrax. However, the extent of copy number variation within the species and how the plasmids are related to pXO1/pXO2-like plasmids in other species of theBacillus cereussensu latogroup remain unclear. To gain new insights into these issues, we sequenced 412B. anthracisstrains representing the total phylogenetic and ecological diversity of the species. Our results revealed thatB. anthracisgenomes carried, on average, 3.86 and 2.29 copies of pXO1 and pXO2, respectively, and also revealed a positive linear correlation between the copy numbers of pXO1 and pXO2. No correlation between the plasmid copy number and the phylogenetic relatedness of the strains was observed. However, genomes of strains isolated from animal tissues generally maintained a higher plasmid copy number than genomes of strains from environmental sources (P< 0.05 [Welch two-sample t test]). Comparisons againstB. cereusgenomes carrying complete or partial pXO1-like and pXO2-like plasmids showed that the plasmid-based phylogeny recapitulated that of the main chromosome, indicating limited plasmid horizontal transfer between or within these species. Comparisons of gene content revealed a closed pXO1 and pXO2 pangenome; e.g., plasmids encode <8 unique genes, on average, and a single large fragment deletion of pXO1 in oneB. anthracisstrain (2000031682) was detected. Collectively, our results provide a more complete view of the genomic diversity ofB. anthracisplasmids, their copy number variation, and the virulence potential of otherBacillusspecies carrying pXO1/pXO2-like plasmids.IMPORTANCEBacillus anthracismicroorganisms are of historical and epidemiological importance and are among the most homogenous bacterial groups known, even though theB. anthracisgenome is rich in mobile elements. Mobile elements can trigger the diversification of lineages; therefore, characterizing the extent of genomic variation in a large collection of strains is critical for a complete understanding of the diversity and evolution of the species. Here, we sequenced a large collection ofB. anthracisstrains (>400) that were recovered from human, animal, and environmental sources around the world. Our results confirmed the remarkable stability of gene content and synteny of the anthrax plasmids and revealed no signal of plasmid exchange betweenB. anthracisand pathogenicB. cereusisolates but rather predominantly vertical descent. These findings advance our understanding of the biology and pathogenomic evolution ofB. anthracisand its plasmids.

scholarly journals Plasmid copy number control: an ever-growing story

2002 ◽  
Vol 37 (3) ◽  
pp. 492-500 ◽  
Author(s):  
Gloria Del Solar ◽  
Manuel Espinosa
Keyword(s):  
Copy Number ◽  
Plasmid Copy Number ◽  
Plasmid Copy ◽  
Copy Number Control

scholarly journals Genetic dissection of centromere function.

1993 ◽  
Vol 13 (6) ◽  
pp. 3156-3166 ◽  
Author(s):  
I G Schulman ◽  
K Bloom
Keyword(s):  
Chromosome Segregation ◽  
Copy Number ◽  
Artificial Chromosome ◽  
Plasmid Copy Number ◽  
Genetic Dissection ◽  
Negative Effects ◽  
Plasmid Copy ◽  
Complex Cells ◽  
Copy Number Control

A system to detect a minimal function of Saccharomyces cerevisiae centromeres in vivo has been developed. Centromere DNA mutants have been examined and found to be active in a plasmid copy number control assay in the absence of segregation. The experiments allow the identification of a minimal centromere unit, CDE III, independently of its ability to mediate chromosome segregation. Centromere-mediated plasmid copy number control correlates with the ability of CDE III to assemble a DNA-protein complex. Cells forced to maintain excess copies of CDE III exhibit increased loss of a nonessential artificial chromosome. Thus, segregationally impaired centromeres can have negative effects in trans on chromosome segregation. The use of a plasmid copy number control assay has allowed assembly steps preceding chromosome segregation to be defined.

scholarly journals A first-takes-all model of centriole copy number control

2020 ◽  
Author(s):  
Marco António Dias Louro ◽  
Mónica Bettencourt-Dias ◽  
Jorge Carneiro
Keyword(s):  
Cell Cycle ◽  
Copy Number Variation ◽  
Cell Population ◽  
Copy Number ◽  
Building Blocks ◽  
Limiting Factors ◽  
Copy Number Control ◽  
Wide Range ◽  
Number Variation ◽  
Rate Limiting

AbstractHow cells control the numbers of its subcellular components is a fundamental question in biology. Given that biosynthetic processes are fundamentally stochastic it is utterly puzzling that some structures display no copy number variation within a cell population. Centriole biogenesis, with each centriole being duplicated once and only once per cell cycle, stands out due to its remarkable fidelity. This is a highly controlled process, which depends on low-abundance rate-limiting factors. How can exactly one centriole copy be produced given the natural variation in the concentration of these key players? Hitherto, tentative explanations of this control evoked lateral inhibition-or phase separation-like mechanisms emerging from the dynamics of these rate-limiting factors, but how centriole number is regulated remains unclear. Here, we propose a novel solution to centriole copy number control based on the assembly of a centriolar scaffold, the cartwheel. We hypothesise that once the first cartwheel is formed it continues to elongate by stacking the intermediate cartwheel building blocks that would otherwise form supernumerary structures. Using probability theory and computer simulations, we show that this mechanism may ensure formation of one and only one cartwheel over a wide range of parameter values at physiologically relevant conditions. By comparison to alternative models, we conclude that the key signatures of this novel mechanism are an increasing assembly time with cartwheel numbers and that stochasticity in cartwheel building blocks should be converted into variation in cartwheel numbers or length, both of which can be tested experimentally.Author summaryCentriole duplication stands out as a biosynthetic process of exquisite fidelity in the noisy world of the cell. Each centriole duplicates exactly once per cell cycle, such that the number of centrioles per cell shows no variance across cells, in contrast with most cellular components that show broadly distributed copy numbers. We propose a new solution to the number control problem. We show that elongation of the first cartwheel, a core centriolar structure, may sequester the building blocks necessary to assemble supernumerary centrioles. As a corollary, the variation in regulatory kinases and cartwheel components across the cell population is predicted to translate into cartwheel length variation instead of copy number variation, which is an intriguing overlooked possibility.

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