AND Gates as Sources of Biological Nonlinearity: Relevance to Genetic Dominance

AND-gating is a mechanism capable of generating nonlinear biological responses because a productive output requires the joint satisfaction of several necessary molecular events. AND gates are considered here in the context of gene expression. Three minimal architectures are discussed, parallel AND gates, kinetic AND gates, and a serial arrangement of AND gates. In a parallel AND gate, output depends on the simultaneous engagement of several modules. In a kinetic AND gate, output requires the completion of several events within a finite time window. In a serial arrangement, the output of one gate becomes the input of the next. These architectures can generate S-shaped responses even when the elementary processes are non-cooperative. Although transcription is our main focus, the same logic applies to other processes. The sigmoidal responses produced by these AND gates provide a phenomenological explanation for how a reduction in the abundance or activity of a dosage-sensitive molecule can generate more-than-proportional downstream effects, a hallmark of haploinsufficiency (HI), a form of dominance. The same AND-gate logic also sheds light on dominant-negative effects, where a mutant protein interferes with its wild-type counterpart. These models illustrate how AND gate architectures can contribute to biological threshold generation and to nonlinear genotype-phenotype relationships, which underlie dominance.