Dynamical Principles of Two-Component Genetic Oscillators 英文参考文献.docVIP

DynamicalPrinciplesofTwo-Component GeneticOscillators Rau′lGuantes1,Juan F.Poyatos2* 1 Instituto Nicola′s Cabrera, Facultad de Ciencias C–XVI, Universidad Auto′noma de Madrid, Madrid, Spain, 2 Evolutionary Systems Biology Initiative, Structural and ComputationalBiologyProgramme,SpanishNationalCancerCentre(CNIO),Madrid,Spain Geneticoscillatorsbasedontheinteractionofasmallsetofmolecularcomponentshavebeenshowntobeinvolvedin theregulationofthecellcycle,thecircadianrhythms,ortheresponseofseveralsignalingpathways.Uncoveringthe functionalpropertiesofsuchoscillatorsthenbecomesimportantfortheunderstandingofthesecellularprocessesand for the characterization of fundamental properties of more complex clocks. Here, we show how the dynamics of a minimaltwo-componentoscillatorisdrasticallyaffectedbyitsgeneticimplementation.Weconsiderarepressorand activatorelementcombinedinasimplelogicalmotif.Whileactivationisalwaysexertedatthetranscriptionallevel, repression is alternatively operating at the transcriptional (Design I) or post-translational (Design II) level. These designs display differences on basic oscillatory features and on their behavior with respect to molecular noise or entrainment by periodic signals. In particular, Design I induces oscillations with large activator amplitudes and arbitrarily small frequencies, and acts as an ‘‘integrator’’ of external stimuli, while Design II shows emergence of oscillationswithfinite,andlessvariable,frequenciesandsmalleramplitudes,anddetectsbetterfrequency-encoded signals (‘‘resonator’’). Similar types ofstimulus responseare observedin neurons, and thus thiswork enables us to connect very different biological contexts. These dynamical principles are relevant for the characterization of the physiologicalrolesofsimpleoscillatormotifs,theunderstandingofcoremachineriesofcomplexclocks,andthebio- engineeringofsyntheticoscillatorycircuits. Citation:GuantesR,PoyatosJF(2006)Dynamicalprinciplesoftwo-componentgeneticoscillators.PLoSComputBiol2(3)