Characterization of the bovine type I IFN locus: rearrangements, expansions, and novel subfamilies

The Type I IFN locus in Bos taurus has undergone significant rearrangement and expansion compared to mouse and human, however, with the constituent genes separated into two sub-loci separated by >700 kb. The IFNW family is greatly expanded, comprising 24 potentially functional genes and at least 8 pseudogenes. The IFNB (n = 6), represented in human and mouse by one copy, are also present as multiple copies in Bos taurus. The IFNT, which encode a non-virally inducible, ruminant-specific IFN secreted by the pre-implantation conceptus, are represented by three genes and two pseudogenes. The latter have sequences intermediate between IFNT and IFNW. A new Type I IFN family (IFNX) of four members, one of which is a pseudogene, appears to have diverged from the IFNA lineage at least 83 million years ago, but is absent in all other sequenced genomes with the possible exception of the horse, a non-ruminant herbivore.In summary, we have provided the first comprehensive annotation of the Type I IFN locus in Bos taurus, thereby providing an insight into the functional evolution of the Type I IFN in ruminants. The diversity and global spread of the ruminant species may have required an expansion of the Type I IFN locus and its constituent genes to provide broad anti-viral protection required for foraging and foregut fermentation.Viruses are constantly evolving to find more effective means to survive and multiply in their host species [1-3]. The immune defense system, in turn, exists in a perpetual state of co-evolution with the pathogens to limit infectious disease, a circumstance often likened to an "arms race." The primary defense mechanism against viruses in vertebrates is Type I IFN (interferon) of the innate immune system [4]. It can reasonably be argued that complex organisms like mammals can only survive as long as immune defenses can adjust to the strategies of invading pathogens. Accordingly, a rapidly evolving, adaptable IFN system is essential to mammals if they are t