Uncovering selection pressures on the IRF gene family in bats' immune system.

Abstract

Unlike other mammals, bats serve as natural reservoirs for several highly pathogenic viruses without exhibiting symptoms of infection. Recent research has explored the complex mechanisms underlying the balance between bats' antiviral defenses and their pathological responses. However, the evolution of the molecular drivers behind bats' antiviral strategies remains largely unknown. Interferon regulatory factors (IRFs) are essential transcription factors that bind to DNA and regulate the expression of numerous genes involved in antiviral defense, inflammation, immune cell differentiation, apoptosis, and oncogenesis. Our research focused on members of the IRF family, using 17 bat species and four terrestrial mammals available in GenBank. We employed CodeML to detect signs of positive selection through three different models. Statistically significant results were obtained for the IRF-1, IRF-4, IRF-5, IRF-6, and IRF-9 genes, which are known to play pivotal roles in various regulation mechanisms. Specifically, IRF-4 and IRF-5 are key in modulating the inflammatory response, while IRF-1 is essential for antiviral defense in bats, and IRF-9 regulates genes activated by type I interferon. Although the role of IRF-6 in these mechanisms requires further investigation in bats, all these genes show signs of positive selection, suggesting an optimization of the processes they regulate. These findings highlight the adaptive role of IRF elements in enhancing, among other things, the bat immune system, potentially improving their resilience and efficacy. Our study not only provides new genetic insights into bats but also underscores the remarkable molecular evolution within this unique group of mammals.