Noisy delay denoises biochemical oscillators

Abstract

Genetic oscillations are generated by delayed transcriptional negative feedback loops, wherein repressor proteins inhibit their own synthesis after a temporal production delay. This delay is distributed because it arises from a sequence of noisy processes, including transcription, translation, folding, and translocation. Because the delay determines repression timing and therefore oscillation period, it has been commonly believed that delay noise weakens oscillatory dynamics. Here, we demonstrate that noisy delay can surprisingly denoise genetic oscillators. Moderate delay noise unexpectedly sharpens oscillation peaks and improves temporal peak reliability without impacting period. We show that this denoising phenomenon occurs in a variety of well-studied genetic oscillators and we use queueing theory to uncover the universal mechanisms that produce it.