Effects of protein maturation on the noise in gene expression

Fluorescent proteins are frequently used as reporters for gene expression in living cells, either by being expressed in tandem with a protein of interest or through the creation of fusion proteins. The data yielded by the fluorescence output are of considerable interest in efforts to formulate quantitative models of cellular behavior underway in fields such as systems biology and synthetic biology. An often neglected aspect of these proteins, however, is their maturation: Before a fluorescent protein can generate a fluorescent signal, it must mature through a series of steps (folding, cyclization, and oxidation) that may take from many minutes to over a day. The presence of these maturation steps creates a distinction between the observed gene expression profile and the actual profile. We examine this effect through a simplified gene expression model and conclude that fluorescent protein maturation can have significant effects on estimates of both the mean protein levels and the variability in gene expression. The model shows that in many regimes, the observed variability will be increased by the maturation process, but indicates the existence of regimes in which the observed variability will actually be less than the true variability of the target protein. The latter effect arises from a low-pass filtering effect introduced by the chain of maturation reactions. The results suggest that the maturation of fluorescent proteins should be taken into account when using such proteins as quantitative indicators of gene expression levels.