Structural conservation of interferon gamma among vertebrates

Interferon gamma (IFN-γ), being the hallmark of the T-cell TH1 response, has been extensively studied with respect to its expression and regulation of immune function. This gene has been extensively characterized in many mammalian species, making it one of the most widely cloned immunoregulatory genes. Recently, the gene has been identified in avian and piscine species and we have identified the gene in the frog genome. Based on these identified DNA sequences, we have constructed an evolutionary history of IFN-γ that shows this molecule can be traced back more than 450 million years ago. Our analysis shows that type II interferon (IFN-γ) function evolved before the tetrapod-fish split, a finding that contrasts earlier studies showing its origins in tetrapods. The IFN-γ gene has undergone a further duplication event in teleosts after the tetrapod-fish split suggesting a specific-evolutionary adaptation in fish. The analyses of IFN-γ, IL-22 and IL-26 genomic region in mammals, chicken, frog and fish reveal an evolutionary conservation of the loci and several regulatory elements controlling IFN-γ gene transcription. Furthermore, across the vertebrata, the first intron of IFN-γ gene contains a polymorphic microsatellite that has been closely correlated with disease susceptibility. Comparative-modeling of IFN-γ structure revealed differences among the representative species but with an overall conservation of the fold, dimer interface and some interactions with the receptor. The structural and functional conservation of IFN-γ suggests the presence of an innate, natural killer (NK) like response or even an adaptive TH1 immune response in lower vertebrates.