Noise-driven heterogeneity in the rate of genetic-variant generation as a basis for evolvability

Molecular biologists have long searched for molecular mechanisms responsible for tuning the rate of genetic-variant generation (RGVG) in fluctuating environments. In spite of several bacterial examples, no regulated variation in the RGVG has been identified in eukaryotic systems. Based notably on the example of industrial and pathogenic yeasts, this article proposes a nonregulated molecular evolutionary mechanism for the appearance of the transient increase of the RGVG in eukaryotic cell populations facing challenging environments. The stochastic nature of gene expression allows a model in which the RGVG in the population can be rapidly tuned as a result of a simple Darwinian process acting on noise-driven heterogeneity in the RGVG from cell to cell. The high flexibility conferred through this model could resolve paradoxical situations, especially concerning the mutator phenotype in cancer cells.