Distinct responses to rare codons in select Drosophila tissues

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• Codon usage bias is known to affect protein production.
• Limited research exists on codon usage's impact on tissue-specific gene expression.
• Understanding these impacts is crucial for comprehending gene regulation.

Purpose of the Study:

• To investigate tissue-specific responses to codon usage bias in *Drosophila melanogaster*.
• To identify distinct tissue capabilities in expressing genes with rare codons.
• To develop a metric for assessing tissue-specific codon adaptation.

Main Methods:

• Utilized codon-modified reporters for an organism-wide screen in *Drosophila*.
• Analyzed protein expression levels in response to varying codon usage.
• Developed and applied the tissue-apparent Codon Adaptation Index (taCAI).

Main Results:

• A sharp decline in protein expression was observed near the limit of rare codon usage.
• Testis and brain tissues uniquely express reporters enriched with rare codons.
• A conserved enrichment of rare codons was found in *Drosophila* and human testis genes.
• Rare codons play a role in a testis-specific gene (*RpL10Aa*), with optimization affecting female fertility.

Conclusions:

• Distinct tissue-specific responses to rare codon usage exist.
• Codon usage bias plays a critical role in tissue biology, particularly in the testis and brain.
• The taCAI metric provides insights into tissue-specific codon adaptation and its evolutionary implications.