A genetic network for the clock of Neurospora crassa

A diverse array of organisms from bacteria to humans may have evolved the ability to tell time in the presence or absence of external environmental cues. In the lowly bread mould, Neurospora crassa, biomolecular reactions involving the white-collar-1 (wc-1), white-collar-2 (wc-2), and frequency (frq) genes and their products constitute building blocks of a biological clock. Here we use genetic network models to explain quantitatively, from a systems perspective, how these building blocks interact, and how a complex trait like clock oscillation emerges from these interactions. We use a recently developed method of genetic network identification to find an ensemble of oscillating network models quantitatively consistent with available RNA and protein profiling data on the N. crassa clock. Predicted key features of the N. crassa clock system are a dynamically frustrated closed feedback loop, cooperativity in frq gene activation, and/or WC-1/WC-2 protein complex deactivation and substantial posttranscriptional enhancement of wc-1 RNA lifetime. Measuring the wc-1 mRNA lifetime provides a critical test of the genetic networks.