The effect of transcription and translation initiation frequencies on the stochastic fluctuations in prokaryotic gene expression

The kinetics of prokaryotic gene expression has been modelled by the Monte Carlo computer simulation algorithm of Gillespie, which allowed the study o f random fluctuations in the number of protein molecules during gene expres sion. The model, when applied to the simulation of LacZ gene expression, is in good agreement with experimental data. The influence of the frequencies of transcription and translation initiation on random fluctuations in gene expression has been studied in a number of simulations in which promoter a nd ribosome binding site effectiveness has been changed in the range of val ues reported for various prokaryotic genes. We show that the genes expresse d from strong promoters produce the protein evenly, with a rate that does n ot vary significantly among cells. The genes with very weak promoters expre ss the protein in "bursts" occurring at random time intervals. Therefore, i f the low level of gene expression results from the low frequency of transc ription initiation, huge fluctuations arise. In contrast, the protein can b e produced with a low and uniform rate if the gene has a strong promoter an d a slow rate of ribosome binding (a weak ribosome binding site). The impli cations of these findings for the expression of regulatory proteins are dis cussed.