Genomic Evidence for the Truly Allelic Nature of the B-Locus Polymorphism of the Rabbit Immunoglobulin Light Chain

Matthyssens, G; Borremans, B.; Hamers, R.; Loo, W. van der

doi:10.1016/b978-0-08-033215-4.50032-7

Cited by 5 publications

(5 citation statements)

References 13 publications

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“…The b4 and b5 genomic sequences differ in their coding regions (330 base pairs) by 39 base-pair substitutions at amino acid replacement sites for only four at synonymous sites, while 96% ofthe base pairs ofthe 3'-untranslated region are conserved (7)(8)(9). A somewhat similar situation exists for Ig C-region genes in other species (33,34).…”

Section: Discussionmentioning

confidence: 76%

“…The different b-locus allotypes (b4, b5, b6, and b9) are associated with multiple amino acid differences throughout the C region of the K L chain. Although alleles can differ by up to 33% in amino acid sequence (6, 7), studies at the genome level have confirmed them as true alleles at a single gene locus (8,9). A most interesting finding was that the nucleotide sequences of b-locus alleles differ almost exclusively by base-pair substitutions causing amino acid replacements (7-9).…”

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confidence: 82%

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Nonrandom allele associations between unlinked protein loci: are the polymorphisms of the immunoglobulin constant regions adaptive?

Loo¹,

Arthur²,

Richardson³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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Consistent linkage disequilibrium was observed between independently segregating protein loci. In natural populations of the European rabbit Oryctolagus cuniculus, highly significant, nonrandom associations between alleles of the constant regions of the immunoglobulin light and heavy chains were found, both within localities and between localities. We suggest that the population genetic data presented here are relevant to the adaptive significance of the genetic polymorphisms of the antibody constant regions.An antibody molecule is composed of two types of polypeptide chains, the immunoglobulin (Ig) heavy (H) and light (L) chains, each type consisting of a variable (V) region and a constant (C) region. The V regions are involved in the recognition and targeting of the (foreign) antigen, while the Ig C regions mediate the antibody functions. In most species studied, including man, genetic polymorphisms have been observed at loci controlling the Ig C regions. Since their discovery (1), the structural and genetic bases of these so-called "Ig allotypes" have been extensively studied, often revealing an unusual degree of complexity (reviewed in ref.2).It is generally agreed that the special genomic mechanisms underlying the variability of the antibody V regions are the outcome of an adaptive process. The biological significance of the genetic diversity of the C regions is, however, not understood. Extensive genetic diversity could, in multiloci systems, be generated by purely random processes (3, 4), but the fact that microorganisms often manipulate the host's immune response by interacting with the C regions of the antibody has suggested that genetic diversity at this level might be part of an immune defense strategy and could affect survival (5).In the European rabbit (Oryctolagus cuniculus L.), serologically defined polymorphisms have been described for both the H chain and L chain (1, 2). As in other species, Hand L-chain polymorphisms segregate as unlinked codominant Mendelian alleles. The different b-locus allotypes (b4, b5, b6, and b9) are associated with multiple amino acid differences throughout the C region of the K L chain. Although alleles can differ by up to 33% in amino acid sequence (6, 7), studies at the genome level have confirmed them as true alleles at a single gene locus (8,9). A most interesting finding was that the nucleotide sequences of b-locus alleles differ almost exclusively by base-pair substitutions causing amino acid replacements (7-9).The two allelic forms e14 and elS of the e locus, which controls the C region of the IgG H chain differ by only one amino acid change (10). Whereas b-locus allotypes seem to evolve very rapidly, phylogenetic data indicate that the serological markers of the e-locus polymorphisms have been conserved in evolution (11-15).These observations might suggest that in rabbit, Ig allotypes are the outcome of adaptive evolution. However, the actual adaptive importance of genetic variation in populations can only be assessed by studying the extent to which t...

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Section: Discussionmentioning

confidence: 76%

mentioning

confidence: 82%

Nonrandom allele associations between unlinked protein loci: are the polymorphisms of the immunoglobulin constant regions adaptive?

Loo¹,

Arthur²,

Richardson³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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“…In the European rabbit (Oryctolagus cuniculus), alleles of the b locus of the constant c,1 region of the immunoglobulin (Ig) light (L-) chain (OUDIN 1960) can differ at up to 40% of their amino acid positions (REISFELD, DRAY and NISONOFF 1965) [reviewed in MACE (1987)l. In spite of this extreme degree of Genetics 1 3 4 171-187 (August, 1993) interallelic divergence, genome analyses have confirmed the rabbit b locus allotypes as true alleles of a single-gene locus (EMORINE et al 1984;MATTHYSSENS et al 1985). The analysis of the patterns of nucleotide substitutions at b locus genes revealed close analogies to those reported for MHC loci, at both the qualitative and quantitative level (VAN DER Loo and VERDOODT 1992).…”

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confidence: 91%

Variance analysis of immunoglobulin alleles in natural populations of rabbit (Oryctolagus cuniculus): the extensive interallelic divergence at the b locus could be the outcome of overdominance-type selection.

Loo¹

1993

Genetics

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Population genetic data are presented which should contribute to evaluation of the hypothesis that the extraordinary evolutionary patterns observed at the b locus of the rabbit immunoglobulin light chain constant region can be the outcome of overdominance-type selection. The analysis of allele correlations in natural populations revealed an excess of heterozygotes of about 10% at the b locus while heterozygote excess was not observed at loci determining the immunoglobulin heavy chain. Data from the published literature, where homozygote advantage was suggested, were reevaluated and found in agreement with data here presented. Gene diversity was evenly distributed among populations and showed similarities with patterns reported for histocompatibility loci. Analysis of genotypic disequilibria revealed strong digenic associations between the leading alleles of heavy and light chain constant region loci in conjunction with trigenic disequilibria corresponding to a preferential association of b locus heterozygosity with the predominant allele of the heavy chain e locus. It is argued that this may indicate compensatory or nonadditive aspects of a putative heterozygosity enhancing mechanism, implying that effects at the light chain might be more pronounced in populations fixed for the heavy chain polymorphism.

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“…The estimation of these parameters for the b locus alleles could therefore be of more general interest as this polymorphism shares or even exaggerates some of the salient features of the MHC loci. Indeed, the coding regions of the CKI gene of the b4 and the b5 allele differ at 39 nucleotide positions, of which 35 are associated with an amino acid replacement, while the associated untranslated regions and noncoding regions show 94-98% homology (BERNSTEIN, SKURLA and MACE 1983;EMORINE et al 1984;MATTHIJSSENS et al 1985). Comparisons including the b9 allele confirmed the four-to-one ratio of replacement versus synonymous substitutions (AKIMENKO, HEIDMANN and ROUCEON 1984;MACE et al 1987).…”

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confidence: 94%

Estimation of gene diversity at the b locus of the constant region of the immunoglobulin light chain in natural populations of European rabbit (Oryctolagus cuniculus) in Portugal, Andalusia and on the Azorean Islands.

Loo¹,

Ferrand²,

Soriguer³

1991

Genetics

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The minimal gene diversity at a locus of the antibody constant region, as estimated in natural populations of rabbit, revealed levels of heterozygosity similar to those reported for the major histocompatibility complex in human and murine populations. Sera of 416 wild rabbits were collected on the Iberian peninsula and on three islands of the Azorean archipelago and analyzed for the occurrence of the serological markers of the b locus of the immunoglobulin light chain. All four serotypes present in domestic rabbits were found in Portugal. They represented less than 50% of the gene pool. In Andalusia this was less than 15% and on the Azorean islands less than 10%. The pronounced and systematic hierarchy in allele frequencies, previously found in populations from the more recent distribution area of the species, was not observed. On the peninsula, the frequencies of the "domestic" alleles were similar, averaging 10%. The Portuguese sample revealed a total heterozygosity of at least 87%. This high value was supported by at least 11 serologically different alleles, none of them occurring at frequencies above 20%. These data are in agreement with an Iberian origin of the European rabbit and strongly suggest the coalescence of b locus allelic lines drawn from Iberian and western populations. The role of balancing selection in the evolution of the b locus polymorphism was further emphasized.

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Genomic Evidence for the Truly Allelic Nature of the B-Locus Polymorphism of the Rabbit Immunoglobulin Light Chain

Cited by 5 publications

References 13 publications

Nonrandom allele associations between unlinked protein loci: are the polymorphisms of the immunoglobulin constant regions adaptive?

Nonrandom allele associations between unlinked protein loci: are the polymorphisms of the immunoglobulin constant regions adaptive?

Variance analysis of immunoglobulin alleles in natural populations of rabbit (Oryctolagus cuniculus): the extensive interallelic divergence at the b locus could be the outcome of overdominance-type selection.

Estimation of gene diversity at the b locus of the constant region of the immunoglobulin light chain in natural populations of European rabbit (Oryctolagus cuniculus) in Portugal, Andalusia and on the Azorean Islands.

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