Influence of gene copy number on self-regulated gene expression
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Abstract: Using an analytically solvable stochastic model, we study the properties of a simple genetic circuit consisting of multiple copies of an self-regulating gene. We analyse how the variation in gene copy number and the mutations changing the auto-regulation strength affect the steady-state distribution of protein concentration. We predict that one-reporter assay, an experimental method where the extrinsic noise level is inferred from the comparison of expression variance of a single and duplicated reporter gene, may give an incorrect estimation of the extrinsic noise contribution when applied to self-regulating genes. We also show that an imperfect duplication of an auto-activated gene, changing the regulation strength of one of the copies, may lead to a hybrid, binary+graded response of these genes to external signal. The analysis of relative changes in mean gene expression before and after duplication suggests that evolutionary accumulation of gene duplications may non-trivially depend on the inherent noisiness of a given gene, quantified by maximal mean frequency of bursts. Moreover, we find that the dependence of gene expression noise on gene copy number and auto-regulation strength may qualitatively differ, e.g. in monotonicity, depending on whether the noise is measured by Fano factor or coefficient of variation. Thus, experimentally-based hypotheses linking gene expression noise and evolutionary optimisation may be ambiguous as they are dependent on the particular function chosen to quantify noise.
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Cited in
(13)- Optimisation of gene expression noise for cellular persistence against lethal events
- A comparative analysis of noise properties of stochastic binary models for a self-repressing and for an externally regulating gene
- Steady-state fluctuations of a genetic feedback loop with fluctuating rate parameters using the unified colored noise approximation
- High cooperativity in negative feedback can amplify noisy gene expression
- Exact and WKB-approximate distributions in a gene expression model with feedback in burst frequency, burst size, and protein stability
- Bifurcation analysis of gene regulatory circuits subject to copy number variation
- How the number of alleles influences gene expression
- Gene expression in self-repressing system with multiple gene copies
- Inference on autoregulation in gene expression with variance-to-mean ratio
- A spatiotemporal master equation model of morphogen transport: local accumulation times, noise measurement and diffusion force
- Stochastic modeling and numerical simulation of gene regulatory networks with protein bursting
- The dynamics of stochastic mono-molecular reaction systems in stochastic environments
- Heavy-tailed distributions in a stochastic gene autoregulation model
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