Biophysical clocks face a trade-off between internal and external noise resistance

Pittayakanchit, Weerapat; Lu, Zhiyue; Chew, Justin; Rust, Michael J.; Murugan, Arvind

doi:10.7554/elife.37624

Cited by 37 publications

(33 citation statements)

References 60 publications

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“…5B). This finding echoes the recent report that the genetic circuit underlying the 396 biological clock often has an architecture to buffer the harmful internal fluctuation of signals 397 while responding to the variation of the functional external stimuli (Pittayakanchit, et al 2018). 398…”

Section: Cell Cycle Genes Have Low Intrinsic But High Extrinsic Noisesupporting

confidence: 63%

Allele-specific single-cell RNA sequencing reveals different architectures of intrinsic and extrinsic gene expression noises

Sun

Zhang

2019

Preprint

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Gene expression noise refers to the variation of the expression level of a gene among isogenic cells in the same environment, and has two sources: extrinsic noise arising from the disparity of the cell state and intrinsic noise arising from the stochastic process of gene expression in the same cell state. Due to the low throughput of the existing method for measuring the two noise components, the architectures of intrinsic and extrinsic expression noises remain elusive. Using allele-specific single-cell RNA sequencing, we here estimate the two noise components of 3975 genes in mouse fibroblast cells. Our analyses verify predicted influences of several factors such as the TATA-box and microRNA targeting on intrinsic and extrinsic noises and reveal gene function-associated noise trends implicating the action of natural selection. These findings unravel differential regulations, optimizations, and biological consequences of intrinsic and extrinsic noises and can aid the construction of desired synthetic circuits.

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Section: Cell Cycle Genes Have Low Intrinsic But High Extrinsic Noisesupporting

confidence: 63%

Allele-specific single-cell RNA sequencing reveals different architectures of intrinsic and extrinsic gene expression noises

Sun

Zhang

2019

Preprint

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“…These findings motivate a stochastic formulation and analysis of coupled genetic oscillators through a combination of Monte Carlo simulations [19], and moment closure schemes [35], [36]. Indeed, recent stochastic analysis of circadian clock models have shown trade-offs between clock precision and molecular noise [33]. As part of future work, we will tailor these results to the segmentation clock and uncover design principles for robust oscillations in spite of low-copy number noise.…”

Section: Concluding Discussionmentioning

confidence: 81%

Analysis of coupled genetic oscillators with delayed positive feedback interconnections

Giordano

Singh

Blanchini

2019

2019 18th European Control Conference (ECC)

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Genetic oscillators have a fundamental role in the regulation not only of intracellular, but also of intercellular functions: for instance, in the segmentation clock, the synchronised oscillation of neighbouring cells generates spatial travelling waves that induce segmentation of precursors of the vertebral column. To investigate this type of phenomena, we consider the behaviour of two genetic negative feedback oscillators, each operating in a different cell, coupled by an intercellular positive-feedback interconnection with delays. The two coupled systems are nominally identical, but can be different due to noise and cell-to-cell variability. When they can be different in general, we study the effect of positive-feedback and of delay in inducing an oscillatory behaviour. When they are identical, we study how the intercellular feedback delay affects the phase difference between the two oscillators.

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“…Yet, each chemical reaction underlying a biochemical oscillator is a stochastic process, which leads to fluctuations in the period of oscillations and affects how accurately it can tell time. In addition to this inherent noise, other aspects of the heterogeneous environment inside a cell can increase the uncertainty in the clock's period [6]. Understanding how biological organisms can robustly maintain the time scales of their clocks in the presence of these fluctuations is hence a central question [7][8][9][10][11], which we address in this letter.…”

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confidence: 99%

High chemical affinity increases the robustness of biochemical oscillations

Junco

Vaikuntanathan

2020

Phys. Rev. E

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Biochemical oscillations are ubiquitous in nature and allow organisms to properly time their biological functions. In this paper, we consider minimal Markov state models of non-equilibrium biochemical networks that support oscillations. We obtain analytical expressions for the coherence and period of oscillations in these networks. These quantities are expected to depend on all details of the transition rates in the Markov state model. However, our analytical calculations reveal that many of these details -specifically, the location and arrangement of the transition ratesbecome irrelevant to the coherence and period of oscillations in the limit where a high chemical affinity drives the system out of equilibrium. This theoretical prediction is confirmed by excellent agreement with numerical results. As a consequence, the coherence and period of oscillations can be robustly maintained in the presence of fluctuations in the irrelevant variables. While recent work has established that increasing energy consumption improves the coherence of oscillations, our findings suggest that it plays the additional role of making the coherence and the average period of oscillations robust to fluctuations in rates that can result from the noisy environment of the cell.In principle, R depends on all the details of the rates k ± i in the network. However, in line with a large body of work that generically connects energy dissipation to accuracy in biophysical processes [20][21][22][23][24][25], it has been suggested that irrespective of these details the affinity bounds the coherence of biochemical oscillations [8,17,18,26]. In particular, Barato and Seifert recently conjectured an upper bound on R as a function of the number of states N and the affinity A of the biochemical network [8]. The bound is saturated when the network is uniform; that is, when all of the counterclockwise (CCW) rates in the network are equal and all of the clockwise (CW) rates are equal. In this uniform limit, the bound tells us that only two variables (N and A) determine R. However, the bound is a weak constraint for non-uniform networks with arbitrary rates [8,17] and hence it is unclear which variables control the time scales of the oscillator in the presence of rate fluctuations. If the time scales depend sensitively on all of the rates in the network, then they might vary dramatically with any fluctuations. Conversely, if they depend on only a small subset of the variables, then they will be robust to any fluctuations arXiv:1808.04914v2 [cond-mat.stat-mech]

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Biophysical clocks face a trade-off between internal and external noise resistance

Cited by 37 publications

References 60 publications

Allele-specific single-cell RNA sequencing reveals different architectures of intrinsic and extrinsic gene expression noises

Allele-specific single-cell RNA sequencing reveals different architectures of intrinsic and extrinsic gene expression noises

Analysis of coupled genetic oscillators with delayed positive feedback interconnections

High chemical affinity increases the robustness of biochemical oscillations

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