Impact of variability in cell generation times on cell-to-cell variability of protein concentrations

Abstract The influence of arbitrary randomness in cell division times on the variability of protein copy numbers within a lineage ensemble has been recently studied, going beyond the contributions of noisy gene expression and partitioning error. However, variability of protein concentrations need separate study, since cell size growth between cell divisions dilute protein concentrations at the same rate as size growth, which also determines mean division times. Here for a model of bursty protein production, we present exact moments (of all orders) of protein concentrations in the cyclo-stationary state, comparing: (i) population and lineage cell ensembles, and (ii) statistics at different cell ages. Two interesting results emerge. While the variance of protein concentration changes with the degree of division time heterogeneity at any cell age, the age-averaged variance is independent of it within lineage ensemble but stays dependent within population ensemble. The skewness within population ensemble is higher in younger cells than within lineage ensemble, and this behavior reverses at older ages. Such a feature vanishes for the age-averaged distribution, with population based skewness always dominating over that of lineage. We also show that mother-daughter correlations in generation times, do not add any significant difference to the results.