Evolutionary perspective of the CAG/CAA interplay coding for pure polyglutamine stretches in proteins

Polyglutamine regions appear in many eukaryotic proteins. Most research on these stretches has focused on humans and primates. We wanted to check whether patterns in their codon usage are shared across a wide taxonomic range. Protein-coding transcripts from 30 eukaryotic model species were searched for stretches of consecutive glutamine codons (CAA/CAG). Most species have higher CAG proportion in longer stretches, except fishes, which either reduced or kept a stable CAG use. CAA codons are located closer to the C-terminal side of the stretches in plants, invertebrates, and tetrapods; fungi showed no bias and fishes showed the opposite. Many tetrapods have codons flanking pure CAG stretches that hint at a mutational control of repeat growth. However, the maximum number of consecutive identical codons within the polyglutamine stretches in most species followed random expectations, with fishes as a main exception. We detected shared patterns in codon usage and position across taxonomically distant species, yet each group retained unique traits. Internal CAA position and external flanking codons both seemed to slow pure CAG expansion. Overall, a mix of random processes and species-specific factors drives how glutamine repeats are shaped and maintained in evolution.