Distinct responses to rare codons in select <i>Drosophila</i> tissues.

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 <i>Drosophila melanogaster</i> 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 <i>Drosophila</i> 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 (taCAI), to reveal a conserved enrichment for rare codon usage in the endogenously expressed genes of both <i>Drosophila</i> and human testis. We further demonstrate a role for rare codons in an evolutionarily young testis-specific gene, <i>RpL10Aa</i>. Optimizing <i>RpL10Aa</i> 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.