Characterization of the bovine type I IFN locus: rearrangements, expansions, and novel subfamilies.
BACKGROUND
The Type I interferons (IFN) have major roles in the innate immune response to viruses, a function that is believed to have led to expansion in the number and complexity of their genes, although these genes have remained confined to single chromosomal region in all mammals so far examined. IFNB and IFNE define the limits of the locus, with all other Type I IFN genes except IFNK distributed between these boundaries, strongly suggesting that the locus has broadened as IFN genes duplicated and then evolved into a series of distinct families.


RESULTS
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.


CONCLUSIONS
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.
Walker
Angela M
AM
Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA. walkeram@missouri.edu
Roberts
R Michael
RM
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D033481:Chromosomes, Mammalian / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D007370:Interferon Type I / Q000145:classification / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D011544:Pseudogenes; D012091:Repetitive Sequences, Nucleic Acid; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D007370:Interferon Type I