Abstract
In mammals, IFIT (Interferon [IFN]-induced proteins with Tetratricopeptide Repeat [TPR] motifs) family genes are involved in many cellular and viral processes, which are tightly related to mammalian IFN response. However, little is known about non-mammalian IFIT genes. In the present study, IFIT genes are identified in the genome databases from the jawed vertebrates including the cartilaginous elephant shark but not from non-vertebrates such as lancelet, sea squirt and acorn worm, suggesting that IFIT gene family originates from a vertebrate ancestor about 450 million years ago. IFIT family genes show conserved gene structure and gene arrangements. Phylogenetic analyses reveal that this gene family has expanded through lineage-specific and species-specific gene duplication. Interestingly, IFN gene family seem to share a common ancestor and a similar evolutionary mechanism; the function link of IFIT genes to IFN response is present early since the origin of both gene families, as evidenced by the finding that zebrafish IFIT genes are upregulated by fish IFNs, poly(I:C) and two transcription factors IRF3/IRF7, likely via the IFN-stimulated response elements (ISRE) within the promoters of vertebrate IFIT family genes. These coevolution features creates functional association of both family genes to fulfill a common biological process, which is likely selected by viral infection during evolution of vertebrates. Our results are helpful for understanding of evolution of vertebrate IFN system.
Highlights
The innate immune response to viral infection is largely dependent on host production of interferons (IFNs) that are a family of cytokines with antiviral, antiproliferative and immunomodulatory properties [1,2]
Predication and Annotation of IFIT Family Genes Four human (H. sapiens) IFIT genes and three mouse (Mus musculus) IFIT genes have been well-characterized [20]; extensive BLAST analyses based on sequence homology with these IFIT proteins were used to search IFIT genes from the genome databases of vertebrates including ten mammalian species, two avian species, one reptilian species, one amphibian species and six fish species (Table 1)
Considering a low level of sequence identity among distant species, two fish IFIT proteins identified previously, crucian carp IFI56 (IFIT1) and IFI58 (IFIT5) [19], were included as query sequences. 42 mammalian genes and 10 zebrafish (D. rerio) genes, which have been annotated in genome databases, were identified as IFIT genes (Table 1)
Summary
The innate immune response to viral infection is largely dependent on host production of interferons (IFNs) that are a family of cytokines with antiviral, antiproliferative and immunomodulatory properties [1,2]. Subsequent studies reveal that IFI56 belongs to a well-conserved gene family, named IFIT (IFN-induced proteins with Tetratricopeptide Repeat (TPR) motifs) family [13]. In addition to IFN treatment, other IFN stimuli including virus infection, doublestranded RNA and lipopolysaccharicdes strongly induce the expression of these family genes, implying pivotal roles under diverse cellular stresses [9,13,14,15,16,17,18]. The possession of multiple TPR domains is believed to endow IFIT proteins on a multitude of effects on cellular and viral functions, including regulation of transcription, translation, antiproliferative effects and negative regulation of host inflammatory and antiviral response [20,21]. IFIT family members have been proven for selectively restricting virus replication by recognition of viral mRNA lacking 29-O methylation or with a 59-triphosphate RNA, likely through its TPR motifs [8,22]
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