Interferon regulatory factor (IRF) was discovered as transcription factors that regulate the transcription of human interferon (IFN)-β at first. In the following studies, more and more IRF members were identified with diverse functions.

The phylogeny pattern of IRF in invertebrate was found vastly different from that in vertebrate where advance immune system evolved, detonating the “big bang” vertebrate immune system. Hence to study the phylogeny and functional diversity of IRF not only gains the knowledge about the gene itself, but also may provide new insight into the evolution of immune system.

Although the lack of key genetic data hinders the study, the Research Group of Fish Phylogenetics and Biogeography led by Prof. HE Shunping at Institute of Hydrobiology of Chinese Academy of Sciences sequenced the genomes and transcriptomes of some ancient fish and lamprey, with a good insight into the vertebrate ancient genome, facilitating IRF study. The study was published in Developmental & Comparative Immunology.

Depending on the similarity of sequence, the researchers identified 148 IRFs in 11 vertebrates and four protochordates. Reconstruction of phylogeny tree revealed that the phylogeny pattern of IRF is more complex but stable in vertebrate than in invertebrate. Together with synteny analysis, the results suggested that vertebrate IRFs were evolved from three predecessors, instead of four as suggested in a previous study.

The second whole-genome duplication (2WGD) followed by some specific gene duplication expanded the vertebrate IRF members from three to six and then to 11. Expression analysis results revealed that IRFs evolved from the same predecessors tend to express differently across tissues, indicating a functional diversity.

Even though positivity selection sign has been detected profoundly across vertebrate IRF members, each predecessor tend to have an “offspring” undergoing purifying selection. This "offspring" may hold the ancient function for the predecessor, freeing the others to evolved new functions.

Integrating previous studies, the researchers inferred that interferon (IFN), an immune gene new bore in the early evolution of vertebrate, could have greatly contributed the expansion of vertebrate IRFs by introducing new gene interaction and new selection pressure into the existed IRF net work. Furthermore, similar mechanism could also be used extensively in the evolution of vertebrate immune system.

The study was supported by the National Natural Science Foundation of China (Grant No. 31372190).

Synteny analysis revealing IRFs and the genes nearby in the genome of representative vertebrate taxa elephant shark, spotted gar, coelacanth and western clawed frog. (Image by IHB)