title: High intralocus variability and interlocus recombination promote immunological diversity in a minimal major histocompatibility system.
abstract: BACKGROUND
  The genes of the major histocompatibility complex (MHC/MH) have attracted considerable scientific interest due to their exceptional levels of variability and important function as part of the adaptive immune system. Despite a large number of studies on MH class II diversity of both model and non-model organisms, most research has focused on patterns of genetic variability at individual loci, failing to capture the functional diversity of the biologically active dimeric molecule. Here, we take a systematic approach to the study of MH variation, analyzing patterns of genetic variation at MH class IIα and IIβ loci of the seahorse, which together form the immunologically active peptide binding cleft of the MH class II molecule.
  
  
  RESULTS
  The seahorse carries a minimal class II system, consisting of single copies of both MH class IIα and IIβ, which are physically linked and inherited in a Mendelian fashion. Both genes are ubiquitously expressed and detectible in the brood pouch of male seahorses throughout pregnancy. Genetic variability of the two genes is high, dominated by non-synonymous variation concentrated in their peptide-binding regions. Coding variation outside these regions is negligible, a pattern thought to be driven by intra- and interlocus recombination. Despite the tight physical linkage of MH IIα and IIβ loci, recombination has produced novel composite alleles, increasing functional diversity at sites responsible for antigen recognition.
  
  
  CONCLUSIONS
  Antigen recognition by the adaptive immune system of the seahorse is enhanced by high variability at both MH class IIα and IIβ loci. Strong positive selection on sites involved in pathogen recognition, coupled with high levels of intra- and interlocus recombination, produce a patchwork pattern of genetic variation driven by genetic hitchhiking. Studies focusing on variation at individual MH loci may unintentionally overlook an important component of ecologically relevant variation.
authors.affiliation: Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. twilson@brooklyn.cuny.edu.|Department of Biology, Brooklyn College and The Graduate Center, City University of New York, 2900 Bedford Avenue, Brooklyn, New York, 11210, USA. twilson@brooklyn.cuny.edu.|Department of Biology, Brooklyn College, 2900 Bedford Avenue, Brooklyn, New York, 11210, USA. twilson@brooklyn.cuny.edu.
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Wilson
authors.affiliation: Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. camilla.whittington@sydney.edu.au.|School of Biological Sciences, University of Sydney, Heydon-Laurence Building A08, Sydney, NSW, 2006, Australia. camilla.whittington@sydney.edu.au.
authors.forename: Camilla M
authors.initials: CM
authors.lastname: Whittington
authors.affiliation: Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. bahr@medmolgen.uzh.ch.|Institute of Medical Molecular Genetics, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland. bahr@medmolgen.uzh.ch.
authors.forename: Angela
authors.initials: A
authors.lastname: Bahr
mesh_terms: D000818:Animals; D005260:Female; D029941:Fish Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005802:Genes, MHC Class II; D014644:Genetic Variation; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D023701:Smegmamorpha / Q000235:genetics* / Q000276:immunology*
chemical_list: D029941:Fish Proteins; D000949:Histocompatibility Antigens Class II