The Major Histocompatibility Complex modulates Batrachochytrium dendrobatidis and Ranavirus infections in three amphibian species

Genetic variation of immune genes is an important component of genetic diversity. Major histocompatibility complex (MHC) genes have been put forward as a model for studying how genetic diversity is maintained and geographically distributed in wild populations. Pathogen-mediated selection processes (i.e., heterozygosity advantage, rare-allele advantage or fluctuating selection) and demography are believed to generate and maintain the extreme diversity of MHC genes observed. However, establishing the relative importance of the different proposed mechanisms has proved extremely difficult, but heterozygote advantage is expected to be more detectable when multiple pathogens are considered simultaneously. Here, we test whether MHC diversity in three amphibian species (Ichthyosaura alpestris, Pleurodeles waltl, and Pelophylax perezi) is driven by pathogen-mediated selection. We examined the relationship between the individual MHC class II exon variability with individual infection status (infected or not), infection intensity, and co-infection of two main amphibian pathogens: Batrachochytrium dendrobatidis (Bd) and Ranavirus sp. (Rv). We found higher MHC class II exon 2 allelic diversity in I.alpestris and P. perezi than in P.waltl but no significant differences in allele frequencies between infection groups. We also observed significant differences in Bd infection intensity between Bd infected individuals and co-infected individuals depending on the number of MHC loci that an individual carries. For I. alpestris, we show stronger evidence for MHC associations with infection intensity and status when individuals carry specific alleles and supertypes. Our results suggest that studying the association between MHC genes and single and co-infected individuals might provide new insights into host-parasite evolution and a better understanding of evolutionary mechanisms driven by MHC diversity. ### Competing Interest Statement The authors have declared no competing interest.