title: Parasite-mediated selection of major histocompatibility complex variability in wild brandt's voles (Lasiopodomys brandtii) from Inner Mongolia, China.
abstract: BACKGROUND
  Genes of the major histocompatibility complex (MHC) exhibit high levels of variability, which is believed to have arisen through pathogen-mediated selection. We investigated the relationship between parasite load and genetic diversity at selectively neutral, non-coding markers (microsatellites) and adaptive genetic variation at a functionally important part of the MHC in six independent natural populations of Brandt's voles (Lasiopodomys brandtii) from two regions of the Xilingol Grassland area of Inner Mongolia.
  
  
  RESULTS
  Two-hundred and fifty-two voles were screened for gastrointestinal parasites, and were assessed for genetic variation. Parasite screening was done through non-invasive fecal egg counts, while allelic diversity was determined via single-stranded conformation polymorphism and DNA sequencing. We detected eight distinct helminth egg morphotypes. A total of 10 microsatellite loci were genotyped and 19 unique MHC class II B alleles were isolated. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB. Neutral and adaptive genetic diversity differed between the six vole populations. To test the main pathogen-driven selection hypotheses for the maintenance of host MHC diversity and parasite species-specific co-evolutionary effects, multivariate approaches (generalized linear mixed models) were used to test for associations between the MHC class II DRB genotype and infections with nematodes. We found no evidence for heterozygote advantage, and overall heterozygosity was lower than expected in the MHC alleles. We identified an association between the parasite load and specific MHC alleles in the voles, and this pattern varied between geographic regions.
  
  
  CONCLUSIONS
  The results suggest that MHC variability in Brandt's voles is maintained by rare allele advantage and fluctuating selection, but the data failed to show any heterozygote advantage effect. Our results add to a growing body of evidence showing that the mode and relative strength of pathogen-driven selection acting on MHC diversity varies within specific wild populations. In addition, our study contributes to the understanding of what maintains MHC diversity, of host-pathogen coevolution and of how genetic diversity is maintained in voles.
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Hongxuan
authors.initials: H
authors.lastname: He
mesh_terms: D000483:Alleles; D000818:Animals; D000835:Animals, Wild / Q000235:genetics / Q000469:parasitology; D003411:Arvicolinae / Q000235:genetics* / Q000469:parasitology; D001483:Base Sequence; D019143:Evolution, Molecular; D005243:Feces / Q000469:parasitology; D014644:Genetic Variation; D006579:Heterozygote; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D018895:Microsatellite Repeats; D008986:Mongolia; D009348:Nematoda / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D009349:Nematode Infections / Q000235:genetics* / Q000469:parasitology; D018807:Polymorphism, Single-Stranded Conformational; D012376:Rodent Diseases / Q000235:genetics* / Q000469:parasitology; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D000949:Histocompatibility Antigens Class II