Abstract

Gig2 (grass carp reovirus (GCRV)-induced gene 2) is first identified as a novel fish interferon (IFN)-stimulated gene (ISG). Overexpression of a zebrafish Gig2 gene can protect cultured fish cells from virus infection. In the present study, we identify a novel gene family that is comprised of genes homologous to the previously characterized Gig2. EST/GSS search and in silico cloning identify 190 Gig2 homologous genes in 51 vertebrate species ranged from lampreys to amphibians. Further large-scale search of vertebrate and invertebrate genome databases indicate that Gig2 gene family is specific to non-amniotes including lampreys, sharks/rays, ray-finned fishes and amphibians. Phylogenetic analysis and synteny analysis reveal lineage-specific expansion of Gig2 gene family and also provide valuable evidence for the fish-specific genome duplication (FSGD) hypothesis. Although Gig2 family proteins exhibit no significant sequence similarity to any known proteins, a typical Gig2 protein appears to consist of two conserved parts: an N-terminus that bears very low homology to the catalytic domains of poly(ADP-ribose) polymerases (PARPs), and a novel C-terminal domain that is unique to this gene family. Expression profiling of zebrafish Gig2 family genes shows that some duplicate pairs have diverged in function via acquisition of novel spatial and/or temporal expression under stresses. The specificity of this gene family to non-amniotes might contribute to a large extent to distinct physiology in non-amniote vertebrates.

Highlights

  • A gene family is composed of homologous genes that are formed by duplication of a single original gene

  • Two rounds of whole genome duplication (WGD) are hypothesized to have occurred on the jawed vertebrate stem, after the divergence of urochordates but before the split between cartilaginous fish and bony vertebrates [2]; teleost fish is suggested to have undergone a third round of WGD termed as fish-specific genome duplication (FSGD) [3]

  • Since the founding gene is named Gig2 [19] and this name is widely used in other literatures [22,29,30,31], this gene family is termed Gig2 gene family

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Summary

Introduction

A gene family is composed of homologous genes that are formed by duplication of a single original gene. Viral infection results in activation of an innate immune response for establishment of a host antiviral state, which is characterized by the production of IFN family proteins and the subsequent transcriptional upregulation of IFN-stimulated genes (ISGs) [7]. Tolllike receptor (TLR) family members (such as TLR3/4/7/8/9) and retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family members recognize different pathogen-associated molecular patterns (PAMPs) to trigger type I IFN signalling [6,7]; IFNregulatory factor (IRF) 3 and IRF7, two IRF family members, directly control expression of IFN family genes [7,8,9]; IFIT (IFNinduced proteins with Tetratricopeptide Repeat (TPR) motifs) family members mediate IFN antiviral effects by selectively restricting the replication of virus lacking 29-O methylation mRNA or with a 59-triphosphate RNA [10,11]. A new strategy has been proposed, in which cells reduce sensitivity to viruses through modification of the viral proteins by poly(ADPribosyl)ation (PARylation), a post-translational modification of proteins that is catalyzed by poly(ADP-ribose) polymerases (PARPs) [12]

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