TY - JOUR
T1 - Closed-form stochastic solutions for non-equilibrium dynamics and inheritance of cellular components over many cell divisions
AU - Johnston, Iain G
AU - Jones, Nick S
PY - 2015/8/8
Y1 - 2015/8/8
N2 - Stochastic dynamics govern many important processes in cellular biology, and an underlying theoretical approach describing these dynamics is desirable to address a wealth of questions in biology and medicine. Mathematical tools exist for treating several important examples of these stochastic processes, most notably gene expression and random partitioning at single-cell divisions or after a steady state has been reached. Comparatively little work exists exploring different and specific ways that repeated cell divisions can lead to stochastic inheritance of unequilibrated cellular populations. Here we introduce a mathematical formalism to describe cellular agents that are subject to random creation, replication and/or degradation, and are inherited according to a range of random dynamics at cell divisions. We obtain closed-form generating functions describing systems at any time after any number of cell divisions for binomial partitioning and divisions provoking a deterministic or random, subtractive or additive change in copy number, and show that these solutions agree exactly with stochastic simulation. We apply this general formalism to several example problems involving the dynamics of mitochondrial DNA during development and organismal lifetimes.
AB - Stochastic dynamics govern many important processes in cellular biology, and an underlying theoretical approach describing these dynamics is desirable to address a wealth of questions in biology and medicine. Mathematical tools exist for treating several important examples of these stochastic processes, most notably gene expression and random partitioning at single-cell divisions or after a steady state has been reached. Comparatively little work exists exploring different and specific ways that repeated cell divisions can lead to stochastic inheritance of unequilibrated cellular populations. Here we introduce a mathematical formalism to describe cellular agents that are subject to random creation, replication and/or degradation, and are inherited according to a range of random dynamics at cell divisions. We obtain closed-form generating functions describing systems at any time after any number of cell divisions for binomial partitioning and divisions provoking a deterministic or random, subtractive or additive change in copy number, and show that these solutions agree exactly with stochastic simulation. We apply this general formalism to several example problems involving the dynamics of mitochondrial DNA during development and organismal lifetimes.
U2 - 10.1098/rspa.2015.0050
DO - 10.1098/rspa.2015.0050
M3 - Article
C2 - 26339194
SN - 1364-5021
VL - 471
SP - 20150050
JO - Royal Society of London. Proceedings A. Mathematical, Physical and Engineering Sciences
JF - Royal Society of London. Proceedings A. Mathematical, Physical and Engineering Sciences
IS - 2180
ER -