IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27070-5.html
   My bibliography  Save this article

Independent control of mean and noise by convolution of gene expression distributions

Author

Listed:
  • Karl P. Gerhardt

    (Rice University)

  • Satyajit D. Rao

    (Rice University)

  • Evan J. Olson

    (Rice University)

  • Oleg A. Igoshin

    (Rice University
    Rice University
    Rice University
    Rice University)

  • Jeffrey J. Tabor

    (Rice University
    Rice University)

Abstract

Gene expression noise can reduce cellular fitness or facilitate processes such as alternative metabolism, antibiotic resistance, and differentiation. Unfortunately, efforts to study the impacts of noise have been hampered by a scaling relationship between noise and expression level from individual promoters. Here, we use theory to demonstrate that mean and noise can be controlled independently by expressing two copies of a gene from separate inducible promoters in the same cell. We engineer low and high noise inducible promoters to validate this result in Escherichia coli, and develop a model that predicts the experimental distributions. Finally, we use our method to reveal that the response of a promoter to a repressor is less sensitive with higher repressor noise and explain this result using a law from probability theory. Our approach can be applied to investigate the effects of noise on diverse biological pathways or program cellular heterogeneity for synthetic biology applications.

Suggested Citation

  • Karl P. Gerhardt & Satyajit D. Rao & Evan J. Olson & Oleg A. Igoshin & Jeffrey J. Tabor, 2021. "Independent control of mean and noise by convolution of gene expression distributions," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27070-5
    DOI: 10.1038/s41467-021-27070-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27070-5
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-27070-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. William J. Blake & Mads KÆrn & Charles R. Cantor & J. J. Collins, 2003. "Noise in eukaryotic gene expression," Nature, Nature, vol. 422(6932), pages 633-637, April.
    2. Long Cai & Nir Friedman & X. Sunney Xie, 2006. "Stochastic protein expression in individual cells at the single molecule level," Nature, Nature, vol. 440(7082), pages 358-362, March.
    3. Dirk Benzinger & Mustafa Khammash, 2018. "Pulsatile inputs achieve tunable attenuation of gene expression variability and graded multi-gene regulation," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    4. Michelle Hung & Emily Chang & Razika Hussein & Katya Frazier & Jung-Eun Shin & Shiori Sagawa & Han N. Lim, 2014. "Modulating the frequency and bias of stochastic switching to control phenotypic variation," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    5. Attila Becskei & Luis Serrano, 2000. "Engineering stability in gene networks by autoregulation," Nature, Nature, vol. 405(6786), pages 590-593, June.
    6. Martin Ackermann & Bärbel Stecher & Nikki E. Freed & Pascal Songhet & Wolf-Dietrich Hardt & Michael Doebeli, 2008. "Self-destructive cooperation mediated by phenotypic noise," Nature, Nature, vol. 454(7207), pages 987-990, August.
    7. Alain R. Bonny & João Pedro Fonseca & Jesslyn E. Park & Hana El-Samad, 2021. "Orthogonal control of mean and variability of endogenous genes in a human cell line," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Tobias May & Lee Eccleston & Sabrina Herrmann & Hansjörg Hauser & Jorge Goncalves & Dagmar Wirth, 2008. "Bimodal and Hysteretic Expression in Mammalian Cells from a Synthetic Gene Circuit," PLOS ONE, Public Library of Science, vol. 3(6), pages 1-7, June.
    2. Abhyudai Singh & Mohammad Soltani, 2013. "Quantifying Intrinsic and Extrinsic Variability in Stochastic Gene Expression Models," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-12, December.
    3. Hui Zhang & Yueling Chen & Yong Chen, 2012. "Noise Propagation in Gene Regulation Networks Involving Interlinked Positive and Negative Feedback Loops," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-8, December.
    4. Benjamin B Kaufmann & Qiong Yang & Jerome T Mettetal & Alexander van Oudenaarden, 2007. "Heritable Stochastic Switching Revealed by Single-Cell Genealogy," PLOS Biology, Public Library of Science, vol. 5(9), pages 1-8, September.
    5. Mohammad Soltani & Cesar A Vargas-Garcia & Duarte Antunes & Abhyudai Singh, 2016. "Intercellular Variability in Protein Levels from Stochastic Expression and Noisy Cell Cycle Processes," PLOS Computational Biology, Public Library of Science, vol. 12(8), pages 1-23, August.
    6. Chen Jia & Ramon Grima, 2024. "Holimap: an accurate and efficient method for solving stochastic gene network dynamics," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Stefano Ciliberti & Olivier C Martin & Andreas Wagner, 2007. "Robustness Can Evolve Gradually in Complex Regulatory Gene Networks with Varying Topology," PLOS Computational Biology, Public Library of Science, vol. 3(2), pages 1-10, February.
    8. Ankit Gupta & Mustafa Khammash, 2022. "Frequency spectra and the color of cellular noise," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Lee, Julian, 2023. "Poisson distributions in stochastic dynamics of gene expression: What events do they count?," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 630(C).
    10. Gita Naseri, 2023. "A roadmap to establish a comprehensive platform for sustainable manufacturing of natural products in yeast," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    11. Manalee Vishnu Surve & Smita Bhutda & Akshay Datey & Anjali Anil & Shalini Rawat & Athira Pushpakaran & Dipty Singh & Kwang Sik Kim & Dipshikha Chakravortty & Anirban Banerjee, 2018. "Heterogeneity in pneumolysin expression governs the fate of Streptococcus pneumoniae during blood-brain barrier trafficking," PLOS Pathogens, Public Library of Science, vol. 14(7), pages 1-29, July.
    12. Kyung H Kim & Herbert M Sauro, 2012. "Adjusting Phenotypes by Noise Control," PLOS Computational Biology, Public Library of Science, vol. 8(1), pages 1-14, January.
    13. Blasi, Monica Francesca & Casorelli, Ida & Colosimo, Alfredo & Blasi, Francesco Simone & Bignami, Margherita & Giuliani, Alessandro, 2005. "A recursive network approach can identify constitutive regulatory circuits in gene expression data," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 348(C), pages 349-370.
    14. Peña, Jorge & Nöldeke, Georg & Lehmann, Laurent, 2014. "Relatedness and synergies of kind and scale in the evolution of helping," Working papers 2014/09, Faculty of Business and Economics - University of Basel.
    15. Simeon D. Castle & Michiel Stock & Thomas E. Gorochowski, 2024. "Engineering is evolution: a perspective on design processes to engineer biology," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    16. Valenti, D. & Tranchina, L. & Brai, M. & Caruso, A. & Cosentino, C. & Spagnolo, B., 2008. "Environmental metal pollution considered as noise: Effects on the spatial distribution of benthic foraminifera in two coastal marine areas of Sicily (Southern Italy)," Ecological Modelling, Elsevier, vol. 213(3), pages 449-462.
    17. Shu Wang & Jia-Ren Lin & Eduardo D Sontag & Peter K Sorger, 2019. "Inferring reaction network structure from single-cell, multiplex data, using toric systems theory," PLOS Computational Biology, Public Library of Science, vol. 15(12), pages 1-25, December.
    18. Paolo Annibale & Stefano Vanni & Marco Scarselli & Ursula Rothlisberger & Aleksandra Radenovic, 2011. "Quantitative Photo Activated Localization Microscopy: Unraveling the Effects of Photoblinking," PLOS ONE, Public Library of Science, vol. 6(7), pages 1-8, July.
    19. Seyed Yahya Anvar & Allan Tucker & Veronica Vinciotti & Andrea Venema & Gert-Jan B van Ommen & Silvere M van der Maarel & Vered Raz & Peter A C ‘t Hoen, 2011. "Interspecies Translation of Disease Networks Increases Robustness and Predictive Accuracy," PLOS Computational Biology, Public Library of Science, vol. 7(11), pages 1-14, November.
    20. Michael W Klymkowsky & Kathy Garvin-Doxas, 2008. "Recognizing Student Misconceptions through Ed's Tools and the Biology Concept Inventory," PLOS Biology, Public Library of Science, vol. 6(1), pages 1-4, January.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27070-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.