Natural History of CXCL16 in Horses: Evidence for Caballine, Non-Caballine Hybridization

Two alleles were identified for the scavenger receptor protein gene, CXCL16. One (susceptibility or S) serves as a receptor for equine arteritis virus (EAV) infection of equine cells while the other (resistance or R) does not. The two alleles differed by 4 non-synonymous mutations in the first exon of the gene with susceptibility dominant to resistance. DNA sequences were compared to the horse reference sequence (Ecab 2.0) for the 2kb region surrounding CXCL16 exon 1 for 9 horses (Equus caballus) (2 R/R, 2 R/S and 5 S/S) and 4 non-caballines [2 asses (E. africanus asinus, E. africanus somaliensis), 1 kiang (E. kiang) and 1 Grevy zebra (E. grevyi) ; all S/S]. High homology was observed for sequences within a 947 bp region for 7 susceptible horses (R/S & S/S) and 4 non-caballine equids. Within this region we observed 13 SNPs common to the susceptible haplotype of horses and all 4 non-caballine equids. This same region also contained 2 SNPs only common to the non-caballine equids and 1 SNP common only to the susceptible horses. The haplotype associated with the resistance was distinct from the susceptibility haplotype and represented by Ecab 2.0. These results suggest a hypothesis for cross-hybridization of caballine and non-caballine species between 400,000 and 600,000 years ago. This would be a remarkable hybridization event considering that the divergence of caballine and non-caballine equids is thought to have taken place over 4.5 million years ago. This suggests cross-hybridization within a genus is a novel way for species to acquire new genes and futher suggests that the co-existence of related species may be an important resource for adaptation and evolution.