Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-? Subtype

Shields, Lauren E.; Jennings, Jordan; Liu, Qinfang; Lee, Jinhwa; Ma, Wenjun; Blecha, Frank; Miller, Laura C.; Sang, Yongming

Cross-species examination of IFN-ω genes indicated that single IFN-ω-like genes are identified in reptiles and birds, and multi-gene IFN-ω subtype are present in most ungulate and bat species (Figures 1, 2 , and Supplemental Excel Sheet). Through phylogenic analysis, we showed that different species of ungulates particularly domestic species such as cattle and pigs experienced individual IFN-ω expansion because IFN-ω genes of each species generally forming into one or two major expanding clusters (2, 8, 9) . Compared to generally one to several IFN-ω genes in other species, cattle and pigs may have 11-25 IFN-ω coding genes as well as about a dozen pseudogenes (Figure 2 ) (8, 9) . Porcine IFN-ω isoforms are orthologous to most, if not all, IFN-ω gene products identified in mammalian species and particularly the complex in cattle (7-9, 17, 18, 27) . This further identifies porcine IFN-ω as a model to analyze functional novelty Frontiers in Immunology | www.frontiersin.org FIGURE 2 | associated taxa clustered together in the bootstrap test (1,000 replicates) is shown next to the branches. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. The evolutionary distances were computed using the p-distance method and are in units of the number of amino acid differences per site. Evolutionary analyses were conducted in MEGA6. The IFN-ω subtype diversified at the similar time of IFN-α, IFN-β, or IFN-ε subtypes for the IFN ancestral molecules identified in jawed fish, but independently evolve further particularly in different mammalian lineage/species. Most, if not all, IFN-ω orthologs form into a big cluster that further bifurcate into two subclusters (labeled with red dots), and the subcluster 1 comprises a majority of IFN-ω orthologs . IFN taxa used: IFNA, IFNB, IFNE, IFNK, IFNL, and IFNW correspond to genes for IFN-α, IFN-β, IFN-ε, IFN-κ, IFN-λ, and IFN -ω, respectively, in classic nomenclature, and stand for relevant IFN protein precursors here (2, (8) (9) (10) .