Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses
(A) The patterns of differential expression of ISGs and IRGs are broadly similar in cells derived from 10 different animal species. Each dot in the panel represents a gene that is differentially expressed in response to type I IFN treatment (S1 Data). (B) Number of ISGs (above line, red arrow) and IRGs (below line, blue arrow) are plotted on the branches of a simplified phylogenetic tree (branch lengths are not shown to scale). ISGs common to every species (n = 62) are located at the root of the tree with an additional 28 ISGs up-regulated by all mammalian species used in this study. At the tips of the tree lie genes that are only up- or down-regulated in an individual species in our study. (C) Normalised correlation matrix showing pairwise comparisons between ISGs (red) and IRGs (blue) of the indicated animal species (S1 Data). (D) A PCA of the log2FC data of the one-to-one orthologs up-regulated by all nine mammalian species used in this study (S1 Data). Each point represents an animal or experiment, coloured according to species. The distribution of the samples reflects expression patterns. Separate animals/experiments cluster according to species, with the pig and human showing similar patterns. (E) A heatmap of the relative expression of the 62 vertebrate core ISGs. The first row (labelled as ‘Interferome’) represents the average log2FC of all up-regulated ISGs for each animal species. Up-regulated paralogs have been averaged in the case of genes for which there are expansions; for example, the rat has two copies of MX1 compared to the single copy in the remaining species (S1 Data). IFN, interferon; IRGs, interferon-repressed genes; ISGs, interferon-stimulated genes; log2FC, log2 fold change; PCA, principal component analysis.