Network motifs underlying different types of phenotypic variation. (A) A negative feedback loop may restrict fluctuations in a protein’s levels and thereby contribute towards the development of an invariant phenotype. For example, protein X may cause the production of protein Y, which downregulates production of X, restricting fluctuations in X’s levels. (B) Phenotypic plasticity may be generated when environmental signals (here sunlight and shade) feed into gene-regulatory networks. In the scenario of shade avoidance, X represents phytochrome-interacting factors (PIFs), while Y represents their downstream transcriptional targets. Perception of full light by activation of phytochrome B (PhyB) causes inactivation or degradation of PIFs (X) (inhibitory arrow), preventing their downstream targets (Y) being activated. In shade, PhyB is inactive, allowing PIF (X) activity (arrow promoting X) and activation of their downstream targets (arrow promoting Y), leading to a change in phenotype. (C) A positive feedback loop can generate a bistable system where stochastic fluctuations in one protein’s levels can cause the noisy transition to a new state of gene expression, leading to intercellular variability in the timing of the transition. (D) If an environmental signal regulates the expression of a component of a positive feedback motif, the phenotype may be both variable within an environment and environmentally sensitive.