Two IFNGR1 homologues in Tetraodon nigroviridis: Origin, expression analysis and ligand-binding preference

• Two IFNGR1s were identified in first fish other than Cypriniformes.
• First mapped two IFNGR1 loci to different H. sapiens and G. gallus chromosomes.
• Suggested the presence of two IFNGR1s is a common phenomenon in teleosts.
• Provided in vitro evidence to support the ligand/receptor model from morpholino D. rerio.

In the present study, the divergent properties of IFNGR1 isoforms (IFNGR1-1 and IFNGR1-2) were characterized in Tetraodon nigroviridis. Despite the structural similarities between these proteins, two T. nigroviridis IFNGR1 homologues differ from each other not only in their primary nucleotide and amino acid sequences but also in their syntenic structure. Genomic analysis demonstrates the conservation of synteny between the fish IFNGR1-2s and IFNGR1s in higher vertebrates; conversely, the IFNGR1-1 has no corresponding conservation of synteny with Gallus gallus and Homo sapiens, suggesting that the two genes were derived from two different origins. Additionally, their different sensitivities to mitogens and recombinant T. nigroviridis IFN-γs were observed. Furthermore, ligand-binding analysis strongly supported the model proposed in Danio rerio, which suggests that IFNGR1-1 is the major component of the IFN-γrel receptor complex; IFN-γ most likely binds to both IFNGR1-2 and IFNGR1-1. This study is a further step towards elucidating the teleostean IFN-γ system, which is different from that in mammals.