Cis-regulatory variants affect gene expression dynamics in yeast

  1. Ching-Hua Shih
  2. Justin Fay  Is a corresponding author
  1. University of Rochester, United States


Evolution of cis-regulatory sequences depends on how they affect gene expression and motivates both the identification and prediction of cis-regulatory variants responsible for expression differences within and between species. While much progress has been made in relating cis-regulatory variants to expression levels, the timing of gene activation and repression may also be important to the evolution of cis-regulatory sequences. We investigated allele-specific expression (ASE) dynamics within and between Saccharomyces species during the diauxic shift and found appreciable cis-acting variation in gene expression dynamics. Within species ASE is associated with intergenic variants, and ASE dynamics are more strongly associated with insertions and deletions than ASE levels. To refine these associations we used a high-throughput reporter assay to test promoter regions and individual variants. Within the subset of regions that recapitulated endogenous expression we identified and characterized cis-regulatory variants that affect expression dynamics. Between species, chimeric promoter regions generate novel patterns and indicate constraints on the evolution of gene expression dynamics. We conclude that changes in cis-regulatory sequences can tune gene expression dynamics and that the interplay between expression dynamics and other aspects expression are relevant to the evolution of cis-regulatory sequences.

Data availability

Genome sequencing and assembly data were deposited into NCBI, see Table S1 and S7 in Supplementary file 1 for accessions. RNA sequencing data were deposited into NCBI's GEO database under GSE165594. Analysis scripts, data and summary files are available at

The following data sets were generated
    1. Shih CH
    2. Fay JC
    (2021) Gene expression dynamics
    Open Science Framework, DOI 10.17605/OSF.IO/Y5748.

Article and author information

Author details

  1. Ching-Hua Shih

    Biology, University of Rochester, ROCHESTER, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Justin Fay

    Biology, University of Rochester, Rochester, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1893-877X


National Institutes of Health (GM080669)

  • Justin Fay

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

Reviewing Editor

  1. Kevin J Verstrepen, VIB-KU Leuven Center for Microbiology, Belgium

Version history

  1. Received: March 17, 2021
  2. Accepted: August 6, 2021
  3. Accepted Manuscript published: August 9, 2021 (version 1)
  4. Version of Record published: August 16, 2021 (version 2)


© 2021, Shih & Fay

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.


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  1. Ching-Hua Shih
  2. Justin Fay
Cis-regulatory variants affect gene expression dynamics in yeast
eLife 10:e68469.

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