Family evolution and functional divergence of bony fish-specific Gig1 homologs

Grass carp reovirus (GCRV)-induced gene 1 (Gig1) is identified initially in crucian carp C. auratus as a novel interferon-stimulated gene (ISG) encoding an antiviral protein and subsequently as the founder member of Gig1 gene family. However, the evolution and function of Gig1 family members remain largely unknown. In this study, genome-wide searchs of 100 vertebrate species representing the main taxonomic lineages revealed that the Gig1 family originated from a common ancestor of bony fish but was completely lost in tetrapods. The Gig1 family is divided into three subfamilies, each with its own characteristics in gain and loss. Compared to subfamily I that originated the earliest and showed no significant change in gene copies, subfamilies II and III were expanded robustly with teleost radiation. Despite no known domains having been identified, motif prediction revealed a conserved motif arrangement in all Gig1 family proteins. Functionally, both zebrafish and grass carp have subfamilies I and II but not subfamily III. However, only certain subfamily II genes were highly induced by viral infection and thus capable of inhibiting viral replication by overexpression and knockout assays. The Japanese rice fish medaka has no subfamily II and, strikingly, one subfamily III gene acquired antiviral feature. Site-directed mutation showed that three leucine residues conserved in the motif 1 were essential for the antiviral role of subfamily II genes in zebrafish. In summary, our results indicate that bony fish-specific Gig1 gene family has been undergoing diversification in expression and function toward virus infection in a given species.