Evolution of MHC class I genes in the European badger (Meles meles)

Abstract

The major histocompatibility complex (MHC) plays a central role in the adaptive immune system and provides a good model with which to understand the evolutionary processes underlying functional genes. Trans-species polymorphism and orthology are both commonly found in MHC genes; however, mammalian MHC class I genes tend to cluster by species. Concerted evolution has the potential to homogenize different loci, whereas birth-and-death evolution can lead to the loss of orthologs; both processes result in monophyletic groups within species. Studies investigating the evolution of MHC class I genes have been biased toward a few particular taxa and model species. We present the first study of MHC class I genes in a species from the superfamily Musteloidea. The European badger (Meles meles) exhibits moderate variation in MHC class I sequences when compared to other carnivores. We identified seven putatively functional sequences and nine pseudogenes from genomic (gDNA) and complementary (cDNA) DNA, signifying at least two functional class I loci. We found evidence for separate evolutionary histories of the α1 and α2/α3 domains. In the α1 domain, several sequences from different species were more closely related to each other than to sequences from the same species, resembling orthology or trans-species polymorphism. Balancing selection and probable recombination maintain genetic diversity in the α1 domain, evidenced by the detection of positive selection and a recombination event. By comparison, two recombination breakpoints indicate that the α2/α3 domains have most likely undergone concerted evolution, where recombination has homogenized the α2/α3 domains between genes, leading to species-specific clusters of sequences. Our findings highlight the importance of analyzing MHC domains separately.

Heterozygosity–fitness correlations in a wild mammal population: accounting for parental and environmental effects

“…; Sin et al. ). Alternatively, females may make cryptic choices according to heterozygosity (Løvlie et al.…”

Pathogen burden, co‐infection and major histocompatibility complex variability in the European badger (Meles meles)

“…We used published primers to amplify exon 3 and exon 2 regions (Sin et al . ,c) that encode the antigen‐binding domain in MHC class I and class II DRB genes, respectively. Previous studies of the badger MHC indicated the presence of at least two class I loci and two class II DRB loci, with seven and four putatively functional sequences identified by transcription analysis, respectively (Sin et al .…”

“…Previous studies of the badger MHC indicated the presence of at least two class I loci and two class II DRB loci, with seven and four putatively functional sequences identified by transcription analysis, respectively (Sin et al . ,c). The MHC sequences were separated by reference strand‐mediated conformation analysis (RSCA) following Sin (), in which each ‘RSCA allele’ was confirmed to be an individual, putatively functional, sequence.…”

“…Consequently, we included eight alleles (three class II DRB: Meme‐DRB*01 , ‐DRB*03 and ‐DRB*04 , Sin et al . ; five class I: Meme‐MHCI*01 , ‐MHCI*02 , ‐MHCI*03 , ‐MHCI*04 and ‐MHCI*07 , Sin et al . ) in the reduced model.…”

“…Although seven putatively functional MHC class I sequences were also identified, from at least two functional class I loci (Sin et al . ), we believe only one locus to be polymorphic (See Fig. S2.1, Supporting information).…”