Introgression from Domestic Goat Generated Variation at the Major Histocompatibility Complex of Alpine Ibex

The major histocompatibility complex (MHC) is a crucial component of the vertebrate immune system and shows extremely high levels of genetic polymorphism. The extraordinary genetic variation is thought to be ancient polymorphisms maintained by balancing selection. However, introgression from related species was recently proposed as an additional mechanism. Here we provide evidence for introgression at the MHC in Alpine ibex (Capra ibex ibex). At a usually very polymorphic MHC exon involved in pathogen recognition (DRBexon 2), Alpine ibex carried only two alleles. We found that one of theseDRBalleles is identical to aDRBallele of domestic goats (Capra aegagrus hircus). We sequenced 2489 bp of the coding and non-coding regions of theDRBgene and found that Alpine ibex homozygous for the goat-typeDRBexon 2 allele showed nearly identical sequences (99.8%) to a breed of domestic goats. Using Sanger and RAD sequencing, microsatellite and SNP chip data, we show that the chromosomal region containing the goat-typeDRBallele has a signature of recent introgression in Alpine ibex. A region of approximately 750 kb including theDRBlocus showed high rates of heterozygosity in individuals carrying one copy of the goat-typeDRBallele. These individuals shared SNP alleles both with domestic goats and other Alpine ibex. In a survey of four Alpine ibex populations, we found that the region surrounding the DRBallele shows strong linkage disequilibria, strong sequence clustering and low diversity among haplotypes carrying the goat-type allele. Introgression at the MHC is likely adaptive and introgression critically increased MHCDRBdiversity in the genetically impoverished Alpine ibex. Our finding contradicts the long-standing view that genetic variability at the MHC is solely a consequence of ancient trans-species polymorphism. Introgression is likely an underappreciated source of genetic diversity at the MHC and other loci under balancing selectio