Distinct responses to rare codons in select Drosophila tissues
- Duke University, United States
- 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.
Article and author information
Author details
Christopher M Counter
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.
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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Distinct responses to rare codons in select Drosophila tissues
eLife 11:e76893.
https://doi.org/10.7554/eLife.76893
