Two interleukin (IL)-15 homologues in fish from two distinct origins.

Here, we report two distinct genes in teleosts that are homologous to interleukin (IL)-15. The two genes, isolated from fugu (Takifugu rubripes), resemble to mammalian IL-15 but differ from IL-2 and IL-21 in their amino acid sequences, the possessing of an extraordinary long signal peptide and more widespread tissue localization. In addition, multiple out-of-frame AUG codons, the negative translational regulators of mammalian IL-15 genes were also detected in the 5'-UTR of the two genes. Fugu IL-15 homologues also contain four conserved cysteines allowing the formation of two disulfide bridges along with four predicted alpha-helices. Genomic analysis showed that one of the fugu IL-15 homologues possessed six coding exons and exhibited a similar exon-intron organization and synteny structure to that of mammalian and chicken IL-15 genes. Conversely, the other fugu IL-15 homologue possesses four exons and exhibits a different synteny structure with that of IL-15, suggesting that the two genes were derived from two different origins. Moreover, the two genes also differ from each other in tissue localizations and in their expression in response to mitogens. The existence of these two IL-15 homologues in telesots was further supported by their characterization in zebrafish Danio rerio, and the green-spotted pufferfish Tetraodon nigroviridis. The discovery of two distinct IL-15 homologues in fish will assist investigations into the evolution of these genes and their relative contribution to the fish immune system.