Living with noise: On the propagation of noise from molecules to phenotype and fitness

In single cells, all molecules fluctuate in concentration because synthesis and degradation events occur asynchronously in a probabilistic manner. Since molecules generally influence multiple reactions, concentration fluctuations can propagate through the entire molecular circuit of a cell. This causes single isogenic cells to vary in their phenotypic properties, which affects the fitness of the associated genotype. Currently, we have a good understanding of how fluctuations arise and propagate in small molecular circuits. Convincing experimental observations exist of fluctuations in the growth and fitness characteristics of single cells. We have however a poor understanding of which molecule concentration fluctuations cause emergent fluctuations in the phenotype of a single cell, how extensive fluctuation propagation is, and what its effects on fitness are. In this opinion paper, we discuss those aspects of current single-cell systems biology.