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BMC Immunol
2010 May 05;11:22. doi: 10.1186/1471-2172-11-22.
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Global characterization of interferon regulatory factor (IRF) genes in vertebrates: glimpse of the diversification in evolution.
Huang B
,
Qi ZT
,
Xu Z
,
Nie P
.
Abstract
BACKGROUND: Interferon 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.
RESULTS: Genome 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.
CONCLUSIONS: In 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.
Figure 1. Genomic structure of IRF-1 in different classes of vertebrates. The gene names listed on the right are as the same as those in Table 1 and in Additional file 1. Exons are expressed as black boxes, and introns as lines. The size of exons is indicated above the boxes in bp, and the size of introns below the lines also in bp. The length of exons indicated as black boxes and of introns indicated as straight lines is proportional to their bp sizes, but the concave-lines are non-proportional. Human (Homo sapiens), mouse (Mus musculus) and dog (Canis familiaris), chicken (Gallus gallus), anole lizard (Anolis carolinensis), frog (Xenopus tropicalis), and zebrafish (Dario rerio) and stickleback (Gasterosteus aculeatus) represent vertebrates in classes of mammal, avian, reptile, amphibian and piscine, as also indicated in Figures 2 to 11.
Figure 2. Genomic structure of IRF-2 in different classes of vertebrates. The gene names, and exon-intron organizations, as well as the vertebrates are expressed in the same way as appeared in Figure 1, and so for Figures 3 to 10. The gene name followed with -seg indicates that the gene only has a sequence segment in database, as also indicated in Table 1 and in Additional file 1, and also in other figures.
Figure 3. Genomic structure of IRF-3 in different classes of vertebrates, except that in chicken the IRF-3 was not found.
Figure 4. Genomic structure of IRF-4 in different classes of vertebrates. Multi-copy genes of IRF-4 were found in teleost fish.
Figure 5. Genomic structure of IRF-5 in different classes of vertebrates.
Figure 6. Genomic structure of IRF-6 in different classes of vertebrates. Two identical IRF-6 genes were found in frog.
Figure 7. Genomic structure of IRF-7 in different classes of vertebrates.
Figure 8. Genomic structure of IRF-8 in different classes of vertebrates.
Figure 9. Genomic structure of IRF-9 in different classes of vertebrates, except that in chicken the IRF-9 was not found.
Figure 10. Genomic structure of IRF-10 in different classes of vertebrates. IRF-10 was not found in human and mouse
Figure 11. Genomic structure of IRF-11 in teleost fish. IRF-11 was only found in teleost, with the full length sequence available for zebrafish IRF-11. The gene name, exon-intron organization, and the fish species are expressed in a same way as in Figures 1 and 2.
Figure 12. Predicted genomic structure of IRF-like genes in the sea urchin Strongylocentrotus purpuratus.
Figure 13. Predicted genomic structure of IRF-like genes and IRF-containing sequence segment in the acorn worm Saccoglossus kowalevskii. The sequence segment was indicated with -seg in the gene name, as also listed in Table 1 and in Additional file 2.
Figure 14. Predicted genomic structure of IRF-like genes and IRF-containing sequence segments in the sea squirt Ciona intestinalis. The sequence segment was indicated with -seg in gene names as also in Table 1 and in Additional file 2.
Figure 15. Predicted genomic structure of IRF-like genes and IRF-containing sequence segment in the lancelet Branchiostoma floridae. The segment was indicated with -seg, and also in Table 1 and in Additional file 2.
Figure 16. IRF-1 gene loci in human, mouse, dog, chicken, anole lizard, frog and zebrafish. Conserved genes are boxed, and vertical lines represent chromosomes; arrows indicate the transcription orientation of genes. Numbers on the side of the lines indicate the distance between genes. PP2CA: protein phosphatase 2 (formerly as 2A), catalytic subunit; SKP1: S-phase kinase-associated protein 1A; TCF7: transcription factor 7 (T-cell specific, HMG-box); VDAC1: voltage-dependent anion channel 1; HSPA4: heat shock 70 kDa protein 4; SLC22A5: solute carrier family 22 (organic cation transporter), member 5; PDLIM4: PDZ and LIM domain 4; ASCL6: acyl-CoA synthetase long-chain family member 6.
Figure 17. IRF-2 gene loci in human, mouse, dog, chicken, anole lizard, frog and zebrafish. The boxed genes, vertical lines and numbers on the side of lines in this figure and in following Figures 18 to 24 are as same as indicated in Figure 16. ING2: Inhibitor of growth protein 2; STOX2: storkhead box 2; Cpase-3: Caspase-3; CDCC111: Coiled-coil domain-containing protein 111; ASCLC1: acyl-CoA synthetase long-chain family member 1; HELT: Hey-like transcription factor; SCF25: ADP/ATP translocase 1/Solute carrier family 25 member 4; PLDP3: PDZ and LIM domain protein 3.
Figure 23. IRF-8 gene loci in human, mouse, dog, chicken, anole lizard, frog and zebrafish. MTHFSD: methenyltetrahydrofolate synthetase domain containing; FOXF1: forkhead box F1; COX4I1: cytochrome c oxidase subunit IV isoform 1, COX4NB: COX4 neighbor; GINS2: GINS complex subunit 2 (Psf2 homologue).
Figure 24. IRF-10 gene loci in human, mouse, dog, chicken, anole lizard, frog and zebrafish. TPX2: microtubule-associated protein homologue (Xenopus laevis); MYLK2: myosin, light polypeptide kinase 2, skeletal muscle; FLKHL18: forkhead-like 18 (Drosophila), DUSP15: dual specificity phosphatase-like 15; XKR7: X Kell blood group precursor related family member 7 homologue, C20orf160: chromosome 20 open reading frame 160, POFUT1: protein O-fucosyltransferase 1, KIF3B: kinesin family member 3B.
Figure 25. Phylogenetic analysis of IRF members in chordates by using neighbor-joining method within Mega4.0 program. Bootstrap values are indicated at nodes. Anole lizard IRF-5-seg, Dog IRF-7-seg and IRF-like gene segments in non-vertebrate deuterostomes were not included in the phylogenetic analysis due to the relatively short sequence lengths, and all IRF or -like genes shown in the tree are listed in Additional files 1 and 2.
Figure 26. A cladistic model for the evolution of IRF family members. Two rounds of duplication of the whole genome are inferred to have occurred by the base of vertebrates, and tandem duplication, perhaps even an extra round of tetraploidization in zebrafish lineage. Subsequent independent gene duplication and/or loss events were marked on the tree. Hs: human Homo sapiens; Mm: mouse Mus musculus; Cf: dog Canis familiaris; Gg: chicken Gallus gallus; Ac: anole lizard Anolis carolinensis; Xt: frog Xenopus tropicalis; Tr: fugu Takifugu rubripes Ga: stickleback Gasterosteus aculeatus; Dr: zebrafish Dario rerio; ND: non-vertebrate deterostomes.
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