Frequency Domain Analysis of Fluctuations of mRNA and Protein Copy Numbers within a Cell Lineage: Theory and Experimental Validation

The stochasticity of gene expression is manifested in the fluctuations of messenger ribonucleic acid and protein copy numbers within a cell lineage over time. While data of this type can be obtained for many generations, most mathematical models are unsuitable to interpret such data since they assum...

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Autores principales: Chen Jia, Ramon Grima
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Publicado: American Physical Society 2021
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spelling oai:doaj.org-article:60f0ef6b28b34bc5b76b2422827e9f902021-12-02T14:35:47ZFrequency Domain Analysis of Fluctuations of mRNA and Protein Copy Numbers within a Cell Lineage: Theory and Experimental Validation10.1103/PhysRevX.11.0210322160-3308https://doaj.org/article/60f0ef6b28b34bc5b76b2422827e9f902021-05-01T00:00:00Zhttp://doi.org/10.1103/PhysRevX.11.021032http://doi.org/10.1103/PhysRevX.11.021032https://doaj.org/toc/2160-3308The stochasticity of gene expression is manifested in the fluctuations of messenger ribonucleic acid and protein copy numbers within a cell lineage over time. While data of this type can be obtained for many generations, most mathematical models are unsuitable to interpret such data since they assume nongrowing cells. Here we develop a theoretical approach that quantitatively links the frequency content of lineage data to subcellular dynamics. We elucidate how the position, height, and width of the peaks in the power spectrum provide a distinctive fingerprint that encodes a wealth of information about mechanisms controlling transcription, translation, replication, degradation, bursting, promoter switching, cell cycle duration, cell division, gene dosage compensation, and cell-size homeostasis. Predictions are confirmed by analysis of single-cell Escherichia coli data obtained using fluorescence microscopy. Furthermore, by matching the experimental and theoretical power spectra, we infer the temperature-dependent gene expression parameters, without the need of measurements relating fluorescence intensities to molecule numbers.Chen JiaRamon GrimaAmerican Physical SocietyarticlePhysicsQC1-999ENPhysical Review X, Vol 11, Iss 2, p 021032 (2021)
institution DOAJ
collection DOAJ
language EN
topic Physics
QC1-999
spellingShingle Physics
QC1-999
Chen Jia
Ramon Grima
Frequency Domain Analysis of Fluctuations of mRNA and Protein Copy Numbers within a Cell Lineage: Theory and Experimental Validation
description The stochasticity of gene expression is manifested in the fluctuations of messenger ribonucleic acid and protein copy numbers within a cell lineage over time. While data of this type can be obtained for many generations, most mathematical models are unsuitable to interpret such data since they assume nongrowing cells. Here we develop a theoretical approach that quantitatively links the frequency content of lineage data to subcellular dynamics. We elucidate how the position, height, and width of the peaks in the power spectrum provide a distinctive fingerprint that encodes a wealth of information about mechanisms controlling transcription, translation, replication, degradation, bursting, promoter switching, cell cycle duration, cell division, gene dosage compensation, and cell-size homeostasis. Predictions are confirmed by analysis of single-cell Escherichia coli data obtained using fluorescence microscopy. Furthermore, by matching the experimental and theoretical power spectra, we infer the temperature-dependent gene expression parameters, without the need of measurements relating fluorescence intensities to molecule numbers.
format article
author Chen Jia
Ramon Grima
author_facet Chen Jia
Ramon Grima
author_sort Chen Jia
title Frequency Domain Analysis of Fluctuations of mRNA and Protein Copy Numbers within a Cell Lineage: Theory and Experimental Validation
title_short Frequency Domain Analysis of Fluctuations of mRNA and Protein Copy Numbers within a Cell Lineage: Theory and Experimental Validation
title_full Frequency Domain Analysis of Fluctuations of mRNA and Protein Copy Numbers within a Cell Lineage: Theory and Experimental Validation
title_fullStr Frequency Domain Analysis of Fluctuations of mRNA and Protein Copy Numbers within a Cell Lineage: Theory and Experimental Validation
title_full_unstemmed Frequency Domain Analysis of Fluctuations of mRNA and Protein Copy Numbers within a Cell Lineage: Theory and Experimental Validation
title_sort frequency domain analysis of fluctuations of mrna and protein copy numbers within a cell lineage: theory and experimental validation
publisher American Physical Society
publishDate 2021
url https://doaj.org/article/60f0ef6b28b34bc5b76b2422827e9f90
work_keys_str_mv AT chenjia frequencydomainanalysisoffluctuationsofmrnaandproteincopynumberswithinacelllineagetheoryandexperimentalvalidation
AT ramongrima frequencydomainanalysisoffluctuationsofmrnaandproteincopynumberswithinacelllineagetheoryandexperimentalvalidation
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