Insights into the complex associations between MHC class II DRB polymorphism and multiple gastrointestinal parasite infestations in the striped mouse

Abstract

Differences in host susceptibility to different parasite types are largely based on the degree of matching between immune genes and parasite antigens. Specifically the variable genes of the major histocompatibility complex (MHC) play a major role in the defence of parasites. However, underlying genetic mechanisms in wild populations are still not well understood because there is a lack of studies which deal with multiple parasite infections and their competition within. To gain insights into these complex associations, we implemented the full record of gastrointestinal nematodes from 439 genotyped individuals of the striped mouse, Rhabdomys pumilio. We used two different multivariate approaches to test for associations between MHC class II DRB genotype and multiple nematodes with regard to the main pathogen-driven selection hypotheses maintaining MHC diversity and parasite species-specific co-evolutionary effects. The former includes investigations of a 'heterozygote advantage', or its specific form a 'divergent-allele advantage' caused by highly dissimilar alleles as well as possible effects of specific MHC-alleles selected by a 'rare allele advantage' (= negative 'frequency-dependent selection'). A combination of generalized linear mixed models (GLMMs) and co-inertia (COIA) analyses made it possible to consider multiple parasite species despite the risk of type I errors on the population and on the individual level. We could not find any evidence for a 'heterozygote' advantage but support for 'divergent-allele' advantage and infection intensity. In addition, both approaches demonstrated high concordance of positive as well as negative associations between specific MHC alleles and certain parasite species. Furthermore, certain MHC alleles were associated with more than one parasite species, suggesting a many-to-many gene-parasite co-evolution. The most frequent allele Rhpu-DRB*38 revealed a pleiotropic effect, involving three nematode species. Our study demonstrates the co-existence of specialist and generalist MHC alleles in terms of parasite detection which may be an important feature in the maintenance of MHC polymorphism.

Figure 1. Frequency of the Rhpu-DRB alleles.

Frequency of the Rhpu-DRB alleles (observed in ≥5 individuals). X marks alleles which were detected as associated with a specific nematode species, resulting from generalized linear mixed models (GLMM) and/or co-inertia (COIA) analysis.

Figure 2. Projection of results of A parasitological and B genetic co-intertia analysis.

Projection of results of (A) parasitological and (B) genetic co-inertia analysis from Rhabdomys pumilio (n = 432). Variables located in a common direction are positively associated whereas those located in the opposite direction are considered as negatively associated. Variables located close to the centre do not structure the data and are not labelled to improve clarity. Nematode A–E = based on egg morphotypes.