Distinct responses to rare codons in select Drosophila tissues

  1. Scott R Allen
  2. Rebeccah K Stewart
  3. Michael Rogers
  4. Ivan Jimenez Ruiz
  5. Erez Cohen
  6. Alain Laederach
  7. Christopher M Counter
  8. Jessica K Sawyer
  9. Donald T Fox  Is a corresponding author
  1. Duke University, United States
  2. University of North Carolina at Chapel Hill, United States

Abstract

Codon usage bias has long been appreciated to influence protein production. Yet, relatively few studies have analyzed the impacts of codon usage on tissue-specific mRNA and protein expression. Here, we use codon-modified reporters to perform an organism-wide screen in Drosophila melanogaster for distinct tissue responses to codon usage bias. These reporters reveal a cliff-like decline of protein expression near the limit of rare codon usage in endogenously expressed Drosophila genes. Near the edge of this limit, however, we find the testis and brain are uniquely capable of expressing rare codon-enriched reporters. We define a new metric of tissue-specific codon usage, the tissue-apparent Codon Adaptation Index, to reveal a conserved enrichment for rare codon usage in the endogenously expressed genes of both Drosophila and human testis. We further demonstrate a role for rare codons in an evolutionarily young testis-specific gene, RpL10Aa. Optimizing RpL10Aa codons disrupts female fertility. Our work highlights distinct responses to rarely used codons in select tissues, revealing a critical role for codon bias in tissue biology.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figs 1, 3, and 5.

The following previously published data sets were used

Article and author information

Author details

  1. Scott R Allen

    Department of Cell Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4809-0493
  2. Rebeccah K Stewart

    Department of Pharmacology and Cancer Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael Rogers

    Department of Pharmacology and Cancer Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ivan Jimenez Ruiz

    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Erez Cohen

    Department of Cell Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Alain Laederach

    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5088-9907
  7. Christopher M Counter

    Department of Pharmacology and Cancer Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0748-3079
  8. Jessica K Sawyer

    Department of Pharmacology and Cancer Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Donald T Fox

    Department of Cell Biology, Duke University, Durham, United States
    For correspondence
    don.fox@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0436-179X

Funding

American Cancer Society (RSG-128945)

  • Donald T Fox

National Science Foundation (GRFP)

  • Scott R Allen

National Institutes of Health (R01CA94184)

  • Christopher M Counter

National Institutes of Health (P01CA203657)

  • Christopher M Counter

National Institutes of Health (R35GM140844)

  • Alain Laederach

National Institutes of Health (R01HL111527)

  • Alain Laederach

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

Reviewing Editor

  1. Alan G Hinnebusch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States

Version history

  1. Preprint posted: January 6, 2022 (view preprint)
  2. Received: January 7, 2022
  3. Accepted: May 5, 2022
  4. Accepted Manuscript published: May 6, 2022 (version 1)
  5. Version of Record published: May 18, 2022 (version 2)

Copyright

© 2022, Allen 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.

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  1. Scott R Allen
  2. Rebeccah K Stewart
  3. Michael Rogers
  4. Ivan Jimenez Ruiz
  5. Erez Cohen
  6. Alain Laederach
  7. Christopher M Counter
  8. Jessica K Sawyer
  9. Donald T Fox
(2022)
Distinct responses to rare codons in select Drosophila tissues
eLife 11:e76893.
https://doi.org/10.7554/eLife.76893

Share this article

https://doi.org/10.7554/eLife.76893

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