Stochastic dynamical constraints in de novo RNA replication.
We study an autocatalytic system coupled to a statistical reservoir. Stochastic effects due to far-from-equilibrium rate fluctuations are analyzed in a self-replicating RNA system catalyzed by Q beta-replicase. We derive the substrate and enzyme concentration dependence of a slow flux term in the rate equations which accounts for the de novo (template-free) synthesis of the initial template strand. The constraints and scaling relations to which the flux is subject follow from a center manifold stochastic reduction of the subordinated degrees of freedom. We thus obtain the induction periods for the onset of amplification in template concentration to detectable levels. These induction periods are regarded as the time needed by far-from-equilibrium fluctuations to drive the system into the center manifold. That is the time it takes the system to restrict itself to the invariant and attractive portion of concentration space. The present study reveals that the fluctuations becomes irrelevant after the initial template molecule is formed, thus elucidating the stochastic nature of the de novo synthesis in contrast with the template-instructed replication process. Experimental work on de novo replication furnishes the evidence for our theoretical findings.
Fernández
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Max-Planck-Institut für biophysikalische Chemie, Göttingen, F.R.G.
D000818:Animals; D002384:Catalysis; D008954:Models, Biological; D011336:Probability; D012313:RNA / Q000096:biosynthesis*; D013269:Stochastic Processes
D012313:RNA