PT  - JOURNAL ARTICLE
AU  - Scott R. Allen
AU  - Rebeccah K. Stewart
AU  - Michael Rogers
AU  - Ivan Jimenez Ruiz
AU  - Erez Cohen
AU  - Alain Laederach
AU  - Christopher M. Counter
AU  - Jessica K. Sawyer
AU  - Donald T. Fox
TI  - Distinct responses to rare codons in select <em>Drosophila</em> tissues
AID  - 10.1101/2022.01.06.475284
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.06.475284
4099  - http://biorxiv.org/content/early/2022/01/06/2022.01.06.475284.short
4100  - http://biorxiv.org/content/early/2022/01/06/2022.01.06.475284.full
AB  - 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 restricting protein expression of an evolutionarily young gene, RpL10Aa, to the Drosophila testis. Rare codon-mediated restriction of this testis-specific protein is critical for female fertility. Our work highlights distinct responses to rarely used codons in select tissues, revealing a critical role for codon bias in tissue biology.Competing Interest StatementThe authors have declared no competing interest.