Variation at functional genes involved in immune response is of increasing concern as wildlife diseases continue to emerge and threaten populations. The amount of standing genetic variation in a population is directly associated with its potential for rapid adaptation to novel environments. For genes in the major histocompatibility complex (MHC), which are crucial in activating the immune response and which have extremely high levels of polymorphism, the genetic variation has been shown to be influenced by both parasite-mediated selection and historical population demography. To better understand the relative roles of parasite-mediated selection and demography on MHC evolution in large populations, I analyzed geographic patterns of variation at the MHC DRB class II locus in mule deer (Odocoileus hemionus). I identified 31 new MHC-DRB alleles which were phylogenetically similar to other cervid MHC alleles, and I found 1 allele that was shared with white-tailed deer (Odocoileus virginianus). I found evidence for selection on the MHC based on high dN/dS ratios, positive neutrality tests, deviations from Hardy-Weinberg Equilibrium (HWE) and greater isolation-by-distance (IBD) than expected under neutrality. However, I also saw evidence that historical demography is important in shaping variation at the MHC, in the similar variation structures between MHC and microsatellites and the lack of significant environmental drivers of variation at either locus. These results show that both natural selection and historical demography are important drivers in the evolution of the MHC in mule deer and may aid in predicting how future adaptation is shaped when this species is confronted with environmental challenges
