Fitness and entropy production in a cell population dynamics with epigenetic phenotype switching

Abstract

Motivated by recent understandings in the stochastic natures of gene expression, biochemical signaling, and spontaneous reversible epigenetic switchings, we study a simple deterministic cell population dynamics in which subpopulations grow with different rates and individual cells can bi‐directionally switch between a small number of different epigenetic phenotypes. Two theories in the past, the population dynamics and thermodynamics of master equations, separately defined two important concepts in mathematical terms: the fitness in the former and the (non‐adiabatic) entropy production in the latter. Both of them play important roles in the evolution of the cell population dynamics. The switching sustains the variations among the subpopulation growth, thus sustains continuous natural selection. As a form of Price’s equation, the fitness increases with (i) natural selection through variations and (ii) a positive covariance between the per capita growth and switching, which represents a Lamarchian‐like behavior. A negative covariance balances the natural selection in a fitness steady state ‐‐‐ “the red queen” scenario. At the same time the growth keeps the proportions of subpopulations away from the “intrinsic” switching equilibrium of individual cells, thus leads to a continuous entropy production. A covariance, between the per capita growth rate and the “chemical potential” of subpopulation, counteracts the entropy production. Analytical results are obtained for the limiting cases of growth dominating switching and vice versa.