Evidence for balancing selection at the major histocompatibility complex in a free-living ruminant

Evidence for selective maintenance of genetic diversity at the major histocompatibility complex (MHC) was investigated in an unmanaged population of Soay sheep on the island of Hirta, St. Kilda, Scotland, Animals were sampled as newborn lambs and between 887 and 1209 individuals were typed at each of five microsatellite markers located either within or flanking the ovine MHC. Markers located within the MHC showed high levels of linkage disequilibrium with each other but not with flanking markers. Hardy-Weinberg proportions were found for all loci; however, two of the three markers within the MHC showed relatively even allele frequency distributions that were unlikely to have resulted from neutrality and suggest the action of recent balancing selection. Sequence polymorphism was examined within DRB, a class II gene immediately adjacent to one of the microsatellite markers, and high correlation of sequence polymorphism with microsatellite length variation was found. An excess of nonsynonymous substitution compared to synonymous substitution was found, indicating the action of balancing selection favoring novel MHC variants and hence increased diversity over a longer time period.