a. Heterozygote advantage
We tested whether MHC diversity is associated with parasite burden at both the individual and the population level. At the individual level, we used parasite richness (i.e., the number of parasite species) to measure parasite burden. Given that MHC genes locate in many genomic loci and often act in a dominant manner in parasite resistance, we used allelic richness (i.e. , the total number of unique MHC alleles found in an individual) in this study to evaluate the level of MHC heterozygosity. We used a mixed effect generalized linear model with Poisson distribution to evaluate the impact of MHC alleles on parasite richness. The fixed effects are the number of MHC alleles and log body length, which is known to affect parasite richness in stickleback (Bolnick et al., 2020) and in other fish species (Calhoun, McDevitt-Galles, & Johnson, 2018). We did not include sex as a main effect because we found no main effect of sex on parasite richness in a previous analysis of this dataset (Bolnick et al., 2020). Sample site was treated as a random effect. In addition, we also evaluated the optimizing hypothesis (i.e. , MHC allelic richness is optimized at an intermediate level, driven by the negative selection pressure to decrease T cell depletion by self-recognition) by adding a quadratic MHC diversity term into the mixed effect model. We considered the interaction between site and the linear and quadratic effects of MHC, using a random slope effect across sites. Statistical support for the model terms was evaluated by AIC.
At the population level, we calculated the mean value of parasite richness and the average number of MHC alleles (per fish) in each site. We used a linear regression model to test if the mean value of parasite richness is associated with the average number of MHC alleles for each site.