Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate

Abstract

Current discussions in evolutionary ecology and conservation genetics focus on the relative importance of using selective neutral markers or markers of coding genes to identify adaptive and evolutionary relevant processes. Genetic diversity might be particularly important in immune genes (e.g., in genes of the major histocompatibility complex, MHC), which are influencing pathogen and parasite resistance. We investigated the effects of neutral versus adaptive genetic variation in parasite resistance in a natural population of fat-tailed dwarf lemurs (Cheirogaleus medius). No association between neutral overall individual genetic diversity and parasite load could be detected. In 149 individuals, we identified 50 MHC class II alleles of the functionally important duplicated DRB locus. The investigation of the functional importance of immune gene (MHC) diversity and parasite selection in natural populations is often problematic due to extensive polymorphism in the MHC genes and restrictions in available sample sizes. Here, for the first time we applied an approach that has been developed in human medical studies. Eleven MHC class II supertypes were identified based on shared antigen-binding similarities. The number of individual MHC supertypes had no influence on the nematode burden. However, we found evidence for a specific MHC supertype (supertype 1) that was linked to infected individuals, a higher number of different nematode infections and high intensity of infection per individual. Moreover, one rare MHC supertype (supertype 7) was revealed to be advantageous with respect to parasite burden. Thus, our results add evidence to the small body of studies that show significant associations between specific MHC constitutions and naturally occurring parasites in the complexity of natural populations.

Host–parasite network structure is associated with community-level immunogenetic diversity

“…At the individual host level, susceptibility to helminths can result from one of the two alleles or from a co-dominant effect of both, also depending on the parasite in question 13 . It is common in studies of MHC diversity to use only alleles/supertypes, rather than genotypes in statistical analyses 5,6,44 . However, owing to the lack of knowledge of the genetic mechanism, and because working with genotypes would create sparse networks, we used supertypes and validated our analyses with genotypes 13 .…”

“…Since previous studies have shown an association between helminthic infections and certain MHC alleles 5,7,35,36 , each individual in the data set (Supplementary Data 1) was genotyped using a portion of the MHC class II DRB exon-2 functional gene that recognizes extracellular parasites such as helminths, by two independent runs of 454 GS-FLX sequencing following the procedure detailed in ref. 18.…”

“…Indeed, several studies have shown that in a host population, parasite diversity-the number and identity of parasite species and their abundance in a host population-is correlated with MHC diversity-the number of MHC alleles in a host and their identity-but not with genetic diversity assessed with neutral markers such as microsatellites or mitochondrial genes 5,10 .…”

“…These genes encode cellsurface glycoproteins that recognize and present foreign antigens, such as those of invading parasites, to T lymphocytes thereby initiating an immune response 4 . Thus, at the host individual level, certain MHC alleles confer resistance/susceptibility to some parasites but not to others [5][6][7] .…”

Selection on MHC: A matter of form over function

“…Now, new evidence comes from the study of a small nocturnal lemur living under natural conditions in western Madagascar. In the paper on page 265, by examining neutral microsatellite diversity, MHC-DRB exon 2 polymorphism and parasite burden, Schwensow et al (2007) found that MHC-DRB genotype is important for resistance to nematode helminths. They conclude that MHC polymorphism is maintained through pathogen-driven frequency-dependent selection in wild fattailed dwarf lemurs (Cheirogaleus medius).…”