Adaptations of Interferon Regulatory Factor 3 with Transition from Terrestrial to Aquatic Life

Monica Angeletti, Wan Ling Nicole Hsu, Nashaat Majo, Hideaki Moriyama, Etsuko N. Moriyama, Luwen Zhang

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Interferon regulatory factor 3 (IRF3) and IRF7 are closely related IRF members and the major factors for the induction of interferons, a key component in vertebrate innate immunity. However, there is limited knowledge regarding the evolution and adaptation of those IRFs to the environments. Two unique motifs in IRF3 and 7 were identified. One motif, GASSL, is highly conserved throughout the evolution of IRF3 and 7 and located in the signal response domain. Another motif, DPHK, is in the DNA-binding domain. The ancestral protein of IRF3 and 7 seemed to possess the DPHK motif. In the ray-finned fish lineage, while the DPHK is maintained in IRF7, the motif in IRF3 is changed to NPHK with a D → N amino acid substitution. The D → N substitution are also found in amphibian IRF3 but not in amphibian IRF7. Terrestrial animals such as reptiles and mammals predominantly use DPHK sequences in both IRF3 and 7. However, the D → N substitution in IRF3 DPHK is again found in cetaceans such as whales and dolphins as well as in marsupials. These observations suggest that the D → N substitutions in the IRF3 DPHK motif is likely to be associated with vertebrate’s adaptations to aquatic environments and other environmental changes.

Original languageEnglish (US)
Article number4508
JournalScientific reports
Issue number1
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • General


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