Abstract

Gene expression noise is an evolvable property of biological systems that describes differences in expression among genetically identical cells in the same environment. Prior work has shown that expression noise is heritable and can be shaped by selection, but the impact of variation in expression noise on organismal fitness has proven difficult to measure. Here, we quantify the fitness effects of altering expression noise for the TDH3 gene in Saccharomyces cerevisiae. We show that increases in expression noise can be deleterious or beneficial depending on the difference between the average expression level of a genotype and the expression level maximizing fitness. We also show that a simple model relating single-cell expression levels to population growth produces patterns consistent with our empirical data. We use this model to explore a broad range of average expression levels and expression noise, providing additional insight into the fitness effects of variation in expression noise.

Data availability

Flow data (FCS files) used to quantify fluorescence levels produced by the 43 TDH3 promoter alleles are available in the FlowRepository (flowrepository.org) under experiment ID FR-FCM-ZY8Y.Raw bright field and fluorescence images, as well as bright field images where cell division events were annotated, are available on Zenodo (https://zenodo.org) with DOI 10.5281/zenodo.1327545All other data are provided as source data and/or supplementary files with the manuscript.

Article and author information

Author details

  1. Fabien Duveau

    Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  2. Andrea Hodgins-Davis

    Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  3. Brian PH Metzger

    Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  4. Bing Yang

    Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  5. Stephen Tryban

    Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  6. Elizabeth A Walker

    Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  7. Tricia Lybrook

    Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  8. Patricia J Wittkopp

    Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, United States
    For correspondence
    wittkopp@umich.edu
    Competing interests
    Patricia J Wittkopp, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7619-0048

Funding

National Institutes of Health (R01GM108826)

  • Patricia J Wittkopp

European Molecular Biology Organization (EMBO ALTF 1114-2012)

  • Brian PH Metzger

National Science Foundation (CB-1021398)

  • Patricia J Wittkopp

National Institutes of Health (1F32GM115198)

  • Andrea Hodgins-Davis

National Institutes of Health (R35GM118073)

  • Patricia J Wittkopp

National Institutes of Health (T32 HG000040)

  • Brian PH Metzger

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2018, Duveau et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 5,252
    views
  • 713
    downloads
  • 64
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Fabien Duveau
  2. Andrea Hodgins-Davis
  3. Brian PH Metzger
  4. Bing Yang
  5. Stephen Tryban
  6. Elizabeth A Walker
  7. Tricia Lybrook
  8. Patricia J Wittkopp
(2018)
Fitness effects of altering gene expression noise in Saccharomyces cerevisiae
eLife 7:e37272.
https://doi.org/10.7554/eLife.37272

Share this article

https://doi.org/10.7554/eLife.37272

Further reading

    1. Cell Biology
    2. Evolutionary Biology
    Paul Richard J Yulo, Nicolas Desprat ... Heather L Hendrickson
    Research Article

    Maintenance of rod-shape in bacterial cells depends on the actin-like protein MreB. Deletion of mreB from Pseudomonas fluorescens SBW25 results in viable spherical cells of variable volume and reduced fitness. Using a combination of time-resolved microscopy and biochemical assay of peptidoglycan synthesis, we show that reduced fitness is a consequence of perturbed cell size homeostasis that arises primarily from differential growth of daughter cells. A 1000-generation selection experiment resulted in rapid restoration of fitness with derived cells retaining spherical shape. Mutations in the peptidoglycan synthesis protein Pbp1A were identified as the main route for evolutionary rescue with genetic reconstructions demonstrating causality. Compensatory pbp1A mutations that targeted transpeptidase activity enhanced homogeneity of cell wall synthesis on lateral surfaces and restored cell size homeostasis. Mechanistic explanations require enhanced understanding of why deletion of mreB causes heterogeneity in cell wall synthesis. We conclude by presenting two testable hypotheses, one of which posits that heterogeneity stems from non-functional cell wall synthesis machinery, while the second posits that the machinery is functional, albeit stalled. Overall, our data provide support for the second hypothesis and draw attention to the importance of balance between transpeptidase and glycosyltransferase functions of peptidoglycan building enzymes for cell shape determination.

    1. Chromosomes and Gene Expression
    2. Evolutionary Biology
    Gülnihal Kavaklioglu, Alexandra Podhornik ... Christian Seiser
    Research Article

    Repression of retrotransposition is crucial for the successful fitness of a mammalian organism. The domesticated transposon protein L1TD1, derived from LINE-1 (L1) ORF1p, is an RNA-binding protein that is expressed only in some cancers and early embryogenesis. In human embryonic stem cells, it is found to be essential for maintaining pluripotency. In cancer, L1TD1 expression is highly correlative with malignancy progression and as such considered a potential prognostic factor for tumors. However, its molecular role in cancer remains largely unknown. Our findings reveal that DNA hypomethylation induces the expression of L1TD1 in HAP1 human tumor cells. L1TD1 depletion significantly modulates both the proteome and transcriptome and thereby reduces cell viability. Notably, L1TD1 associates with L1 transcripts and interacts with L1 ORF1p protein, thereby facilitating L1 retrotransposition. Our data suggest that L1TD1 collaborates with its ancestral L1 ORF1p as an RNA chaperone, ensuring the efficient retrotransposition of L1 retrotransposons, rather than directly impacting the abundance of L1TD1 targets. In this way, L1TD1 might have an important role not only during early development but also in tumorigenesis.