Major histocompatibility complex variation in the endangered Przewalski's horse

The major histocompatibility complex (MHC) is a fundamental part of the ver tebrate immune system, and the high variability in many MHC genes is though t to play an essential role in recognition of parasites. The Przewalski's h orse is extinct in the wild and all the living individuals descend from 13 founders, most of whom were captured around the turn of the century. One of the primary genetic concerns in endangered species is whether they have am ple adaptive variation to respond to novel selective factors. In examining 14 Przewalski's horses that are broadly representative of the living animal s, we found six different class II DRB major histocompatibility sequences. The sequences showed extensive nonsynonymous variation, concentrated in the putative antigen-binding sites, and little synonymous variation. Individua ls had from two to four sequences as determined by single-stranded conforma tion polymorphism (SSCP) analysis. On the basis of the SSCP data, phylogene tic analysis of the nucleotide sequences, and segregation in a family group , we conclude that four of these sequences are from one gene (although one sequence codes for a nonfunctional allele because it contains a stop codon) and two other sequences are from another gene. The position of the stop co don is at the same amino-acid position as in a closely related sequence fro m the domestic horse. Because other organisms have extensive variation at h omologous loci, the Przewalski's horse may have quite low variation in this important adaptive region.