Spatially variable coevolution between a haemosporidian parasite and the MHC of a widely distributed passerine

The environment shapes host–parasite interactions, but how environmental variation affects the diversity and composition of parasite‐defense genes of hosts is unresolved. In vertebrates, the highly variable major histocompatibility complex (MHC) gene family plays an essential role in the adaptive immune system by recognizing pathogen infection and initiating the cellular immune response. Investigating MHC‐parasite associations across heterogeneous landscapes may elucidate the role of spatially fluctuating selection in the maintenance of high levels of genetic variation at the MHC. We studied patterns of association between an avian haemosporidian blood parasite and the MHC of rufous‐collared sparrows (Zonotrichia capensis) that inhabit environments with widely varying haemosporidian infection prevalence in the Peruvian Andes. MHC diversity peaked in populations with high infection prevalence, although intra‐individual MHC diversity was not associated with infection status. MHC nucleotide and protein sequences associated with infection absence tended to be rare, consistent with negative frequency‐dependent selection. We found an MHC variant associated with a ~26% decrease in infection probability at middle elevations (1501–3100 m) where prevalence was highest. Several other variants were associated with a significant increase in infection probability in low haemosporidian prevalence environments, which can be interpreted as susceptibility or quantitative resistance. Our study highlights important challenges in understanding MHC evolution in natural systems, but may point to a role of negative frequency‐dependent selection and fluctuating spatial selection in the evolution of Z. capensis MHC.