Ga. Gutierrez-espeleta et al., Is the decline of desert bighorn sheep from infectious disease the result of low MHC variation?, HEREDITY, 86, 2001, pp. 439-450
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.