Adaptive evolution of interferon induced protein with tetratricopeptide repeats 5(IFIT5) in birds

Abstract Background : Previous studies have revealed that wild birds are reservoirs and mobile vectors of viruses, many of which cause illness and mortality in domestic bird and humans. In birds, the invasion of viruses will quickly trigger the innate immune mechanism induced by interferon (IFN). As IFN-stimulated genes (ISGs), the IFIT gene family plays an important role in innate immunity. However, only IFIT5 of the IFIT gene family exists in birds, and the direction and strength of selection acting on IFIT5 are largely unknown. Results : Here, we studied the selection on IFIT5 based on the coding sequence (CDS) data of 20 birds. We identified 12 persistent positive selection sites (PSS), other sites suffered purifying selection and neutral selection; probably due to functional constraints. We also found humans have only 3PSS (189,197and 295), likely due to having more IFIT gene family member that can cooperate to resist virus invasion. The 12 PSS located in the closed clamp structure of the IFIT5 protein, except for position 45. In particular, 3 PSS (335, 342 and 367) were located in the TPR domain, which implied their important roles in virus recognition. We only found 2 episodic PSS (30,332) in Passeriformes, indicating episodic selection pressure in Passeriformes lineage. The positive selection of IFIT5 might provide a theoretical basis for the pathogen-host interaction in birds. Conclusions : We found that the diversity of IFIT5 domains in birds, and that the PSS of IFIT5 is the joint influence of functional domain conservation and the pressure of virus evolution.We speculated that persistent PSS may affect the antiviral function of IFIT5, especially in the region of closed clamp structure. These results lay a theoretical foundation for the further study of the antiviral immune mechanism of IFIT5 in birds.