Frequency spectrum of chemical fluctuation: A probe of reaction mechanism and dynamics

PLoS Comput Biol. 2019 Sep 16;15(9):e1007356. doi: 10.1371/journal.pcbi.1007356. eCollection 2019 Sep.

Abstract

Even in the steady-state, the number of biomolecules in living cells fluctuates dynamically, and the frequency spectrum of this chemical fluctuation carries valuable information about the dynamics of the reactions creating these biomolecules. Recent advances in single-cell techniques enable direct monitoring of the time-traces of the protein number in each cell; however, it is not yet clear how the stochastic dynamics of these time-traces is related to the reaction mechanism and dynamics. Here, we derive a rigorous relation between the frequency-spectrum of the product number fluctuation and the reaction mechanism and dynamics, starting from a generalized master equation. This relation enables us to analyze the time-traces of the protein number and extract information about dynamics of mRNA number and transcriptional regulation, which cannot be directly observed by current experimental techniques. We demonstrate our frequency spectrum analysis of protein number fluctuation, using the gene network model of luciferase expression under the control of the Bmal 1a promoter in mouse fibroblast cells. We also discuss how the dynamic heterogeneity of transcription and translation rates affects the frequency-spectra of the mRNA and protein number.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Computational Biology / methods*
  • Computer Simulation
  • Gene Regulatory Networks* / genetics
  • Gene Regulatory Networks* / physiology
  • Mice
  • Models, Biological*
  • Proteins / analysis
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Single-Cell Analysis
  • Stochastic Processes

Substances

  • Proteins
  • RNA, Messenger

Grants and funding

This research was supported by the Creative Research Initiative Project program (NRF-015R1A3A2066497) funded by the National Research Foundation of the Korean government. S. Hong acknowledges the National Research Foundation grant (NRF-2018R1A2B6009246) funded by the Korean government. S. Song also acknowledges the Chung-Ang University Graduate Research Scholarship in 2016. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.