How does evolution tune biological noise?

Part of molecular and phenotypic differences between individual cells, between body parts, or between individuals can result from biological noise. This source of variation is becoming more and more apparent thanks to the recent advances in dynamic imaging and single-cell analysis. Some of these studies showed that the link between genotype and phenotype is not strictly deterministic. Mutations can change various statistical properties of a biochemical reaction, and thereby the probability of a trait outcome. The fact that they can modulate phenotypic noise brings up an intriguing question: how may selection act on these mutations? In this review, we approach this question by first covering the evidence that biological noise is under genetic control and therefore a substrate for evolution. We then sequentially inspect the possibilities of negative, neutral, and positive selection for mutations increasing biological noise. Finally, we hypothesize on the specific case of H2A.Z, which was shown to both buffer phenotypic noise and modulate transcriptional efficiency.