The Low Noise Limit in Gene Expression.
Protein noise measurements are increasingly used to elucidate biophysical parameters. Unfortunately noise analyses are often at odds with directly measured parameters. Here we show that these inconsistencies arise from two problematic analytical choices: (i) the assumption that protein translation rate is invariant for different proteins of different abundances, which has inadvertently led to (ii) the assumption that a large constitutive extrinsic noise sets the low noise limit in gene expression. While growing evidence suggests that transcriptional bursting may set the low noise limit, variability in translational bursting has been largely ignored. We show that genome-wide systematic variation in translational efficiency can-and in the case of E. coli does-control the low noise limit in gene expression. Therefore constitutive extrinsic noise is small and only plays a role in the absence of a systematic variation in translational efficiency. These results show the existence of two distinct expression noise patterns: (1) a global noise floor uniformly imposed on all genes by expression bursting; and (2) high noise distributed to only a select group of genes.
Gladstone Institute of Virology and Immunology, San Francisco, California, United States of America; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Roy D
RD
Dar
Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America; Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee, Knoxville, Tennessee, United States of America; Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, New York, United States of America.
Brandon S
BS
Razooky
Gladstone Institute of Virology and Immunology, San Francisco, California, United States of America; QB3: California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, California, United States of America; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
Leor S
LS
Weinberger
Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, Tennessee, United States of America.
Chris D
CD
Cox
Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America; Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee, Knoxville, Tennessee, United States of America; Department of Materials Science and Engineering, University of Tennessee, Knoxville, Tennessee, United States of America.
Michael L
ML
Simpson
D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D008957:Models, Genetic; D014176:Protein Biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
D029968:Escherichia coli Proteins