A multi-species comparison of type-i interferon response reveals fundamental properties of the mammalian innate immune system

Cross-species transmission of pathogens can result in large disease outbreaks. One barrier to the successful infection of a new host is the innate immune response mediated by type-I interferon (IFN), whereby hundreds of interferon stimulated genes (ISGs) are differentially expressed upon IFN signalling. We determined common and unique properties of the ISG repertoire for ten vertebrate species of zoonotic importance by RNAseq-based transcriptomic analysis. We identified a 'core' of 62 genes that were consistently upregulated across all ten vertebrate species and revealed the ancestral functions associated with the mammalian IFN response. We show that gene expansion contributes to the evolution of the IFN system, and that interferomes are shaped by lineage-specific pressures. Our approach also allows the identification of genes downregulated by IFN and suggests that epigenetic regulation of transcription is a fundamental aspect of the IFN response. Lastly, we developed a web server tool to facilitate mining of the dataset.