Biological Sources of Intrinsic and Extrinsic Noise in cI Expression of Lysogenic Phage Lambda.

Genetically identical cells exposed to homogeneous environment can show remarkable phenotypic difference. To predict how phenotype is shaped, understanding of how each factor contributes is required. During gene expression processes, noise could arise either intrinsically in biochemical processes of gene expression or extrinsically from other cellular processes such as cell growth. In this work, important noise sources in gene expression of phage λ lysogen are quantified using models described by stochastic differential equations (SDEs). Results show that DNA looping has sophisticated impacts on gene expression noise: When DNA looping provides autorepression, like in wild type, it reduces noise in the system; When the autorepression is defected as it is in certain mutants, DNA looping increases expression noise. We also study how each gene operator affects the expression noise by changing the binding affinity between the gene and the transcription factor systematically. We find that the system shows extraordinarily large noise when the binding affinity is in certain range, which changes the system from monostable to bistable. In addition, we find that cell growth causes non-negligible noise, which increases with gene expression level. Quantification of noise and identification of new noise sources will provide deeper understanding on how stochasticity impacts phenotype.