High Cooperativity in Negative Feedback can Amplify Noisy Gene Expression

Burst-like synthesis of protein is a significant source of cell-to-cell variability in protein levels. Negative feedback is a common example of a regulatory mechanism by which such stochasticity can be controlled. Here we consider a specific kind of negative feedback, which makes bursts smaller in t...

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Bibliographic Details
Published in:Bulletin of mathematical biology Vol. 80; no. 7; pp. 1871 - 1899
Main Authors: Bokes, Pavol, Lin, Yen Ting, Singh, Abhyudai
Format: Journal Article
Language:English
Published: New York Springer US 01.07.2018
Springer Nature B.V
Subjects:
Algorithms
Animals
Bursting strength
Cell Biology
Coefficient of variation
Computer Simulation
Feedback
Feedback, Physiological
Gene Expression
Humans
Life Sciences
Load
Markov Chains
Mathematical and Computational Biology
Mathematical Concepts
Mathematics
Mathematics and Statistics
Models, Genetic
Negative feedback
Original Article
Protein biosynthesis
Protein Biosynthesis - genetics
Proteins
Regulatory mechanisms (biology)
Single-Cell Analysis
Stochastic Processes
Stochasticity
Variation
Asymptotic expansions
Negative feedback
60K40
Stochastic gene expression
Delayed production
41A60
Protein bursting
92C40
ISSN:0092-8240, 1522-9602, 1522-9602
Online Access:Get full text
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Summary:Burst-like synthesis of protein is a significant source of cell-to-cell variability in protein levels. Negative feedback is a common example of a regulatory mechanism by which such stochasticity can be controlled. Here we consider a specific kind of negative feedback, which makes bursts smaller in the excess of protein. Increasing the strength of the feedback may lead to dramatically different outcomes depending on a key parameter, the noise load, which is defined as the squared coefficient of variation the protein exhibits in the absence of feedback. Combining stochastic simulation with asymptotic analysis, we identify a critical value of noise load: for noise loads smaller than critical, the coefficient of variation remains bounded with increasing feedback strength; contrastingly, if the noise load is larger than critical, the coefficient of variation diverges to infinity in the limit of ever greater feedback strengths. Interestingly, feedbacks with lower cooperativities have higher critical noise loads, suggesting that they can be preferable for controlling noisy proteins.
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ISSN:0092-8240
1522-9602
1522-9602
DOI:10.1007/s11538-018-0438-y