Evolutionary Regression and Species-Specific Codon Usage of TLR15

Area of Science:

• Immunology
• Evolutionary Biology
• Genomics

Background:

• Toll-like receptors (TLRs) are crucial innate immune sensors.
• Most TLR subfamilies are conserved across vertebrates.
• TLR15, unique to birds and reptiles, presented an evolutionary puzzle.

Purpose of the Study:

• To investigate the evolutionary origin and functional conservation of TLR15.
• To explore the reasons behind TLR15's restricted distribution in vertebrates.

Main Methods:

• Phylogenetic and synteny analyses to identify TLR15 orthologs.
• Cloning and functional assays (NF-κB activation) of TLR15 from various species.
• Analysis of TLR15 expression levels and codon usage.

Main Results:

• TLR15 orthologs found in birds, reptiles, and a shark, indicating an ancient origin predating tetrapod divergence.
• TLR15 consistently activated by proteases across studied species, demonstrating conserved function.
• Variable TLR15 expression linked to species-specific codon usage, unlike conserved TLRs.

Conclusions:

• TLR15 is an ancient protease-activated receptor with conserved function in birds and reptiles.
• Widespread loss and variable expression suggest evolutionary regression of TLR15 in most vertebrates.
• Species-specific codon bias significantly impacts TLR15 expression levels.