Fig. 1.

Nonlinearities at multiple levels across development modulate variance. a General model of a nonlinear genotype–phenotype map where the amount of a particular developmental process (e.g., cell survival, proliferation, and Fgf signaling) determines mean phenotype. Note that the same amount of variation in the mechanism (“wild-type” gene expression—blue vertical bar, “mutant” gene expression—red vertical bar) can generate vastly different amounts of phenotypic variation. This model yields a canalized region where variance is buffered (“wild-type” shape variation, blue horizontal bar) and an area where canalization is lost (“mutant” shape variation, red horizontal bar). b Hypothetical model of how nonlinear genotype–phenotype relationships are generated at multiple biological levels. The top left panel shows that gene expression will relate linearly to cranial phenotype. The top mid panel shows that changes in the gene regulatory network (GRN) downstream to Fgf8 respond either nonlinearly, driving change in the phenotypic mean (red line), or act in a compensatory manner, buffering the effect of variation in Fgf8 (green line). The top right panel shows that morphology will relate nonlinearly to Fgf8 level, potentially due to nonlinear changes in the underlying cell biological processes. Variances are influenced at the level at which the nonlinearity arises (lower panels)