Evolution of the Interferon Regulatory Factor Family

Abstract

The interferon regulatory factors (IRFs) are a family of transcription factors that play central roles in immune defence and stress responses. All IRF proteins share a deoxyribonucleic acid (DNA)‐binding domain. IRF genes first appeared in the last common metazoan ancestor. In sponges, placozoans and ctenophores the number and diversity of the IRF family are limited. In cnidarians and bilaterians, the IRF genes diversified into the IRF1 and IRF4 branches. The IRF family, especially the IRF4 genes, expanded several times in distinct groups of bilaterians to include as many as 14 family members. In nematodes and insects, IRF genes were eliminated or mutated beyond recognition. The 10 vertebrate IRF genes arose by the 2‐fold whole genome duplication in early vertebrates. Repetitive expansions, diversifications or contractions of IRF family suggest the changing selection pressure in the evolution of the metazoan defence systems.

Key Concepts:

  • The interferon regulatory factors are a family of transcription factors that function as major regulators of host defence in vertebrates.

  • IRF genes first appeared in the last common metazoan ancestor.

  • IRF genes are present in all five basal groups of metazoans: sponges, placozoans, comb jellies, cnidarians and bilaterians.

  • IRF genes have two evolutionary conserved domains, the DNA‐binding domain and the IRF association domain and both are already present in ancient sponges.

  • In cnidarians and bilaterians, the IRF genes diversified into the IRF1 and IRF4 branches.

  • The IRF family expanded several times in distinct groups of bilaterians (molluscs, cephalochordates, tunicates and vertebrates).

  • IRF genes were eliminated or mutated beyond recognition in nematodes and insects.

  • The 10 members of the vertebrate IRF family originated in early vertebrates as a result of 2‐fold genome duplication.

  • Some IRF genes were eliminated in certain vertebrate species, whereas additional IRF family members were detected in fishes.

  • Although the function of the IRF family in vertebrates has been studied in considerable detail, very little is known about the functions of invertebrate IRF genes.

Keywords: interferon regulatory factors; evolution; metazoan‐specific origin; expansion and contraction of gene family; 2R hypothesis

Figure 1.

Structure of vertebrate IRF family members. Schematic representation of protein structure of the four vertebrate IRF subfamilies with major functional domains indicated (DBD–DNA‐binding domain, IAD–IRF association domain). Ten IRF family members (IRF1–IRF10) belonging to these four subfamilies are identified. The tree on the left indicates the evolutionary relationship of the subfamilies and the two supergroups (IRF1‐SG and IRF4‐SG) are shown on the right.

Figure 2.

Evolution of IRF family in nonbilaterian Metazoa. Unrooted neighbour‐joining evolutionary tree of the IRFDNA‐binding domain (DBD) protein sequences constructed with ClustalX (2.0) is presented in rectangular cladogram shape. IRF proteins are represented by the species abbreviation and a number, with these numbers independently assigned for each invertebrate species. These numbers do not imply any relationship to the 10 numbered vertebrate IRF genes. Four vertebrate IRF proteins (HS1, GG1, HS4 and GG4) are also shown in the cladogram to indicate their relationship to IRF proteins of nonbilaterian Metazoa. Species abbreviations: AQ, Amphimedon queenslandica; GG, Gallus gallus; HM, Hydra magnipapillata; HS, Homo sapiens; MS, Metridium senile; NV, Nematostella vectensis; OC, Oscarella carmela; PP, Pleurobrachia pileus and TA, Trichoplax adhaerens. The IRFDBD sequences used for the construction of the phylogenetic tree were published previously (Nehyba et al., ).

Figure 3.

Evolution of IRF family in Bilateria. Unrooted neighbour‐joining evolutionary trees of the IRFDNA‐binding domain (DBD) protein sequences constructed with ClustalX (2.0) are presented in radial phylogram shape. The scale bar represents the number of amino acid substitutions per site. Different background colours indicate the division of IRF proteins into two supergroups (IRF1‐SG and IRF4‐SG) based on their relationship to vertebrate IRF genes (Nehyba et al., ). The third group of highly divergent arthropodean IRF proteins most likely related to IRF4‐SG is also indicated. IRF proteins are represented by the species abbreviation and a number, with these numbers independently assigned for each invertebrate species. These numbers do not imply any relationship to the 10 numbered vertebrate IRF proteins. Species abbreviations: AC, Aplysia californica; BF, Branchiostoma floridae; CI, Ciona intestinalis; EG, Echinococcus granulosus; ErS, Eriocheir sinensis; GG, Gallus gallus; HS, Homo sapiens; IS, Ixodes scapularis; LG, Lottia gigantea; MC, Mytilus californianus; MG, Mesobuthus gibbosus; ScM, Schmidtea mediterranea; SK, Saccoglossus kowalevskii; SM, Schistosoma mansoni and SP, Strongylocentrotus purpuratus. The IRFDBD sequences used for the construction of the phylogenetic tree were published previously (Nehyba et al., ).

Figure 4.

Evolution and origin of vertebrate IRF family members. (a) Unrooted neighbour‐joining evolutionary tree of the IRF full‐length protein sequences constructed with ClustalX (2.0) is presented in radial phylogram shape. Sequences of some proteins may be truncated. The scale bar represents the number of amino acid substitutions per site. Different background colours indicate division of IRF proteins into two supergroups (IRF1‐SG and IRF4‐SG). IRF proteins are represented by the species abbreviation and a number. All identified family members are shown for human, chicken and zebrafish, while only one member (IRF10) is shown for dog and cow. The gene initially identified in zebrafish as irf11 (Entrez GeneID: 792160) is actually more closely related to IRF1 genes of other vertebrate species than the zebrafish gene initially identified as irf1 (GeneID: 678604). The gene with the ID number 678604 likely represents a distinct family member and the protein encoded by this gene is indicated in the figure as IRF11 (Huang et al., ). Species abbreviations: BT, Bos taurus (cow); CF, Canis lupus familiaris (dog); DR, Danio rerio (zebrafish); GG, Gallus gallus (chicken) and HS, Homo sapiens (human). The accession numbers of the IRF proteins are: BT10‐XP_875833, CF10‐XP_852252, DR1‐NP_991310, DR2‐NP_001008614, DR2a‐NP_996937, DR3‐XP_693269, DR4a‐NP_001116182, DR4L‐XP_698990, DR4b‐XP_697730, DR5‐NP_998040, DR6‐NP_956892, DR7‐NP_956971, DR8‐NP_001002622, DR9‐NP_991273, DR10‐NP_998044, DR11‐NP_001035442, GG1‐Q90876, GG2‐Q98925, GG4‐NP_989630, GG5‐NP_001026758, GG6‐XP_417990, GG7‐Q90643, GG8‐Q90871, GG10‐NP_989889, HS1‐P10914, HS2‐P14316, HS3‐Q14653, HS4‐Q15306, HS5‐Q13568, HS6‐O14896, HS7‐Q92985, HS8‐Q02556 and HS9‐Q00978. (b) Two alternative hypotheses for the evolution of the four vertebrate IRF subfamilies (IRF1‐G, IRF3‐G, IRF4‐G and IRF5‐G) and individual family members. Alternative 1 though more complicated is supported by the assignment of IRF3‐G and IRF5‐G into two different ancestral chordate linkage groups (Nehyba et al., ). Numbers in green ovals indicate three steps in evolutionary process: 1, division into IRF1‐SG and IRF4‐SG at prebilaterian stage; 2, gene duplication(s) in prevertebrate deuterostomian or early vertebrate and 3, 2‐fold whole genome duplication (WGD) in early vertebrate. In each group, MO(2) indicates two missing ohnologues, that is, genes expected to be generated by 2‐fold WGD but not detected.

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Nehyba, Jiří, Hrdličková, Radmila, and Bose, Henry R(Sep 2010) Evolution of the Interferon Regulatory Factor Family. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022874]