Regulation of noise in the expression of a single gene

摘要: Stochastic mechanisms are ubiquitous in biological systems. Biochemical reactions that involve small numbers of molecules intrinsically noisy, being dominated by large concentration fluctuations 1‐3 . This intrinsic noise has been implicated the random lysis/lysogeny decision bacteriophage-λ 4 , loss synchrony circadian clocks 5,6 and decrease precision cell signals7. We sought to quantitatively investigate extent which occurrence molecular within single cells (biochemical noise) could explain variation gene expression levels between a genetically identical population (phenotypic noise). have isolated biochemical contribution phenotypic from other sources carrying out series differential measurements. varied independently rates transcription translation fluorescent reporter chromosome Bacillus subtilis, we measured resulting changes characteristics. report these two parameters, increased translational efficiency is predominant source noise. effect consistent with stochastic model proteins produced sharp bursts. Our results thus provide first direct experimental evidence origin noise, demonstrating level an isogenic can be regulated genetic parameters. selected as our system single-copy chromosomal inducible promoter. As estimated 50‐80% bacterial genes transcriptionally 8 this typifies majority naturally occurring genes, allowing extended natural incorporated copy reporter, green protein (gfp), into B. subtilis. chose integrate gfpinto itself, rather than form plasmids, plasmid number 9,10 act additional unwanted Transcriptional was using isopropyl-β-D-thiogalactopyranoside (IPTG)‐inducible promoter, Pspac, upstream gfp, varying IPTG growth medium. Translational