title: Allelic variation at the VHa locus in natural populations of rabbit (Oryctolagus cuniculus, L.).
abstract: The large interallelic distances between the three rabbit Ig V(H)a lineages, a1, a2 and a3, suggest that the persistence time of the V(H)a polymorphism could amount to 50 million years, which is much longer than that of MHC polymorphisms. Rabbit originated in the Iberian Peninsula where two subspecies coexist, one of which is confined to Southwestern Iberia (Oryctolagus cuniculus algirus). We studied the V(H) loci in the original species range to obtain a better understanding of the evolutionary history of this unusual polymorphism. Serological surveys revealed that sera from the subspecies algirus, when tested with V(H)a locus-specific alloantisera, showed either cross-reactivity ("a-positive" variants) or no reaction at all ("a-blank"). Using RT-PCR, we determined 120 sequences of rearranged V(H) genes expressed in seven algirus rabbits that were typed as either a-positive or a-blank. The data show that the V(H) genes transcribed in a-positive rabbits are closely related to the V(H)1 alleles of domestic rabbits. In contrast, a-blank rabbits were found to preferentially use V(H) genes that, although clearly related to the known V(H)a genes, define a new major allotypic lineage, designated a4. The a4 sequences have hallmark rabbit V(H)a residues together with a number of unprecedented amino acid changes in framework region 2 and 3. The net protein distances between the V(H)a4 and the V(H)a1, a2, and a3 lineages were 20, 29, and 21% respectively. We conclude that at least four distantly related lineages of the rabbit V(H)a locus exist, one of which seems to be endemic in the Iberian range.
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Campus Agrário de Vairão, Rua Padre Armando Quintas, Vairão, Portugal.
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Esteves
authors.forename: Dennis
authors.initials: D
authors.lastname: Lanning
authors.forename: Nuno
authors.initials: N
authors.lastname: Ferrand
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Knight
authors.forename: Shi-Kang
authors.initials: SK
authors.lastname: Zhai
authors.forename: Wessel
authors.initials: W
authors.lastname: van der Loo
mesh_terms: D000483:Alleles; D022981:Allelic Imbalance / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000835:Animals, Wild; D000916:Antibody Diversity / Q000235:genetics; D004272:DNA, Mitochondrial / Q000032:analysis; D005785:Gene Conversion / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005819:Genetic Markers / Q000276:immunology*; D014644:Genetic Variation / Q000276:immunology*; D007126:Immunoglobulin Allotypes / Q000097:blood / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D011817:Rabbits / Q000235:genetics* / Q000276:immunology*; D017422:Sequence Analysis, DNA; D013045:Species Specificity
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers; D007126:Immunoglobulin Allotypes; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region