Quantifying gene expression variability arising from randomness in cell division times

D.J. Antunes, Abhyudai Singh

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)
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Abstract

The level of a given mRNA or protein exhibits significant variations from cell-to-cell across a homogeneous population of living cells. Much work has focused on understanding the different sources of noise in the gene-expression process that drive this stochastic variability in gene-expression. Recent experiments tracking growth and division of individual cells reveal that cell division times have considerable inter-cellular heterogeneity. Here we investigate how randomness in the cell division times can create variability in population counts. We consider a model by which mRNA/protein levels in a given cell evolve according to a linear differential equation and cell divisions occur at times spaced by independent and identically distributed random intervals. Whenever the cell divides the levels of mRNA and protein are halved. For this model, we provide a method for computing any statistical moment (mean, variance, skewness, etcetera) of the mRNA and protein levels. The key to our approach is to establish that the time evolution of the mRNA and protein statistical moments is described by an upper triangular system of Volterra equations. Computation of the statistical moments for physiologically relevant parameter values shows that randomness in the cell division process can be a major factor in driving difference in protein levels across a population of cells. © 2014 Springer-Verlag Berlin Heidelberg.

Original languageEnglish
Pages (from-to)437-463
Number of pages27
JournalJournal of Mathematical Biology
Volume71
Issue number2
DOIs
Publication statusPublished - Aug 2015

Keywords

  • Asymptotic levels
  • Non-genetic heterogeneity cell division times
  • Statistical moments
  • Stochastic gene expression
  • Volterra equations

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