Making sense of snapshot data: ergodic principle for clonal cell populations
File(s)20170467.full.pdf (1.11 MB)
Published version
Author(s)
Thomas, P
Type
Journal Article
Abstract
Population growth is often ignored when quantifying gene expression levels across clonal cell populations. We develop a framework for obtaining the molecule number distributions in an exponentially growing cell population taking into account its age structure. In the presence of generation time variability, the average acquired across a population snapshot does not obey the average of a dividing cell over time, apparently contradicting ergodicity between single cells and the population. Instead, we show that the variation observed across snapshots with known cell age is captured by cell histories, a single-cell measure obtained from tracking an arbitrary cell of the population back to the ancestor from which it originated. The correspondence between cells of known age in a population with their histories represents an ergodic principle that provides a new interpretation of population snapshot data. We illustrate the principle using analytical solutions of stochastic gene expression models in cell populations with arbitrary generation time distributions. We further elucidate that the principle breaks down for biochemical reactions that are under selection, such as the expression of genes conveying antibiotic resistance, which gives rise to an experimental criterion with which to probe selection on gene expression fluctuations.
Date Issued
2017-11-29
Date Acceptance
2017-10-30
Citation
Journal of the Royal Society Interface, 2017, 14
ISSN
1742-5662
Publisher
Royal Society, The
Journal / Book Title
Journal of the Royal Society Interface
Volume
14
Copyright Statement
© 2017 The Author(s).
Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
License URL
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Royal Commission for the Exhibition of 1851
Grant Number
EP/N014529/1
Subjects
population dynamics
population snapshots
stochastic gene expression
MD Multidisciplinary
General Science & Technology
Publication Status
Published
Article Number
20170467