Global characterization of interferon regulatory factor (IRF) genes in vertebrates: Glimpse of the diversification in evolution

Abstract

BackgroundInterferon regulatory factors (IRFs), which can be identified based on a unique helix-turn-helix DNA-binding domain (DBD) are a large family of transcription factors involved in host immune response, haemotopoietic differentiation and immunomodulation. Despite the identification of ten IRF family members in mammals, and some recent effort to identify these members in fish, relatively little is known in the composition of these members in other classes of vertebrates, and the evolution and probably the origin of the IRF family have not been investigated in vertebrates.ResultsGenome data mining has been performed to identify any possible IRF family members in human, mouse, dog, chicken, anole lizard, frog, and some teleost fish, mainly zebrafish and stickleback, and also in non-vertebrate deuterostomes including the hemichordate, cephalochordate, urochordate and echinoderm. In vertebrates, all ten IRF family members, i.e. IRF-1 to IRF-10 were identified, with two genes of IRF-4 and IRF-6 identified in fish and frog, respectively, except that in zebrafish exist three IRF-4 genes. Surprisingly, an additional member in the IRF family, IRF-11 was found in teleost fish. A range of two to ten IRF-like genes were detected in the non-vertebrate deuterostomes, and they had little similarity to those IRF family members in vertebrates as revealed in genomic structure and in phylogenetic analysis. However, the ten IRF family members, IRF-1 to IRF-10 showed certain degrees of conservation in terms of genomic structure and gene synteny. In particular, IRF-1, IRF-2, IRF-6, IRF-8 are quite conserved in their genomic structure in all vertebrates, and to a less degree, some IRF family members, such as IRF-5 and IRF-9 are comparable in the structure. Synteny analysis revealed that the gene loci for the ten IRF family members in vertebrates were also quite conservative, but in zebrafish conserved genes were distributed in a much longer distance in chromosomes. Furthermore, all ten different members are clustered in respectively different clades; but the IRF-11 was clustered with one in sea urchin.ConclusionsIn vertebrates, the ten well-characterized IRF family members shared a relatively high degree of similarity in genomic structure and syntenic gene arrangement, implying that they might have been evolved in a similar pattern and with similar selective pressure in different classes of vertebrates. Genome and/or gene duplication, and probably gene shuffling or gene loss might have occurred during the evolution of these IRF family members, but arrangement of chromosome or its segment might have taken place in zebrafish. However, the ten IRF family members in vertebrates and those IRF-like genes in non-vertebrate deuterostomes were quite different in those analyzed characters, as they might have undergone different patterns of evolution.

Interferon regulatory factor 10 (IRF10): Cloning in orange spotted grouper, Epinephelus coioides, and evolutionary analysis in vertebrates

“…It is clearly illustrated in this study, as reported in our previous study [26], that IRF10 was clustered with IRF4, IRF8 and IRF9, indicating that these four IRF members might have been derived from a common ancestor [25,27,45,46]. As illustrated in Fig.…”

“…As reported in our previous study [26], IRF10 gene was identified in this study in all other major groups of vertebrates, except in most primate and rodent species in which IRF10 appears only as a pseudogene or is overlapped with the downstream DUSP15 gene [25,26], although more genomic sequences of vertebrates have been released and searched (see Supplemental Table 1 and [26]). To our surprise, a transcript encoding IRF10 was found in O. garnettii genome database.…”

“…Among the eleven members of the IRF family, IRF1 to IRF10 are present in vertebrates, ranging from fish to mammal, while IRF11 was found only in teleost fish [24,26]. As reported in our previous study [26], IRF10 gene was identified in this study in all other major groups of vertebrates, except in most primate and rodent species in which IRF10 appears only as a pseudogene or is overlapped with the downstream DUSP15 gene [25,26], although more genomic sequences of vertebrates have been released and searched (see Supplemental Table 1 and [26]).…”

“…However, the expression pattern of bird IRF10 is different from its closest relative, and this IRF may be involved in later stages of antiviral responses in birds [25]. In our previous study, IRF10 has been identified in genomes of a wide range of vertebrates, from mammals to teleosts, except in human (Homo sapiens) and mouse (Mus musculus) [26]. In teleosts, IRF10 has been reported only from olive flounder (Paralichthys olivaceus), zebrafish (Dario rerio) and Atlantic cod (Gadus morhua) [27e30].…”

Fish IRF6 is a positive regulator of IFN expression and involved in both of the MyD88 and TBK1 pathways

“…In fish, there are 11 IRF members in total [18]. Fish homologs are also crucial for IFN regulation as transcription factors, for Most IRFs, containing an N-terminal DNA binding domain (DBD) and a C-terminal IRF association domain (IAD), mediating interaction with target gene promoters and association with other proteins, respectively [19,20].…”