8 research outputs found
Kernel Architecture of the Genetic Circuitry of the Arabidopsis Circadian System
A wide range of organisms features molecular machines, circadian clocks,
which generate endogenous oscillations with ~24 h periodicity and thereby
synchronize biological processes to diurnal environmental fluctuations.
Recently, it has become clear that plants harbor more complex gene regulatory
circuits within the core circadian clocks than other organisms, inspiring a
fundamental question: are all these regulatory interactions between clock genes
equally crucial for the establishment and maintenance of circadian rhythms? Our
mechanistic simulation for Arabidopsis thaliana demonstrates that at least half
of the total regulatory interactions must be present to express the circadian
molecular profiles observed in wild-type plants. A set of those essential
interactions is called herein a kernel of the circadian system. The kernel
structure unbiasedly reveals four interlocked negative feedback loops
contributing to circadian rhythms, and three feedback loops among them drive
the autonomous oscillation itself. Strikingly, the kernel structure, as well as
the whole clock circuitry, is overwhelmingly composed of inhibitory, rather
than activating, interactions between genes. We found that this tendency
underlies plant circadian molecular profiles which often exhibit
sharply-shaped, cuspidate waveforms. Through the generation of these cuspidate
profiles, inhibitory interactions may facilitate the global coordination of
temporally-distant clock events that are markedly peaked at very specific times
of day. Our systematic approach resulting in experimentally-testable
predictions provides insights into a design principle of biological clockwork,
with implications for synthetic biology.Comment: Supplementary material is available at the journal websit