Is the decline of desert bighorn sheep from infectious disease the result of low MHC variation?

Bighorn sheep populations have greatly declined in numbers and distribution since European settlement, primarily because of high susceptibility to inf ectious diseases transmitted to them from domestic livestock. It has been s uggested that low variation at major histocompatibility complex (MHC) genes , the most important genetic aspect of the vertebrate immune system, may re sult in high susceptibility to infectious disease. Therefore, we examined g enetic polymorphism at a MHC gene (Ovca-DRB) in a large sample, both numeri cally and geographically, of bighorn sheep. Strikingly, there were 21 diffe rent alleles that showed extensive nucleotide and amino acid sequence diver gence. In other words, low MHC variation does not appear to be the basis of the high disease susceptibility and decline in bighorn sheep. On the other hand, analysis of the pattern of the MHC polymorphism suggested that nonsy nonymous substitutions predominated, especially at amino acids in the antig en-binding site. The average overall heterozygosity for the 16 amino acid p ositions that are part of the antigen binding site is 0.389 whereas that fo r the 67 amino acid positions not involved with antigen binding is 0.076. T hese findings imply that the diversity present in this gene is functionally significant and is, or has been, maintained by balancing selection. To exa mine the evolution of DRB alleles in related species, a phylogenetic analys is including other published ruminant (Bovidae and Cervidae) species, was c arried out. An intermixture of sequences from bighorn sheep, domestic sheep , goats, cattle, bison, and musk ox was observed supporting trams-species p olymorphism for these species. To reconcile the species and gene trees for the 104 sequences examined, 95 'deep coalescent' events were necessary, ill ustrating the importance of balancing selection maintaining variation over speciation events.