Abstract
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.
Highlights
The innate immune system comprises the cells and the mechanisms that defend the host from infection by other organisms in a non-specific manner
Because the D → N substitutions in Interferon regulatory factor 3 (IRF3) DPHK are mainly associated with animals adapted to aquatic environments, the NPHK motif in IRF3 proteins may play a role in their adaptive evolution during land-water transitions
While in all five amphibian IRF7 proteins we examined, the motif A is conserved with DPHK, the sequence was changed in four amphibian IRF3 proteins with three having NPHK sequences
Summary
The innate immune system comprises the cells and the mechanisms that defend the host from infection by other organisms in a non-specific manner. The secondary transition that happened in some species from terrestrial to aquatic environments was significant These environmental transitions presented numerous challenges to ancestral vertebrates, and necessitated adaptations in various anatomies and biological processes including innate immune systems[20,21]. To study how these genes responded to environmental transitions during vertebrate evolution, we collected IRF3 and 7 protein sequences from all available vertebrate species and examined how their sequences changed during evolution. Because the D → N substitutions in IRF3 DPHK are mainly associated with animals adapted to aquatic environments (ray-finned fish, amphibians, and cetaceans), the NPHK motif in IRF3 proteins may play a role in their adaptive evolution during land-water transitions
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