Abstract
Is there a selective advantage of increased diversity at one immunoglobulin locus when diversity at another locus is low? A previous paper demonstrated excess heterozygosity at the rabbit light chain b locus when heterozygosity was low at the heavy chain constant region e locus. Here we consider the reverse situation by analyzing allele distributions at heavy chain loci in populations fixed for the light chain b locus. We analyzed the a locus that encodes the predominantly expressed heavy chain variable region, and the d and e loci that control different parts of the Ig gamma class constant region. While there was excess heterozygosity, genetic differentiation between localities was extensive and was most pronounced for females. This was in marked contrast with observations in areas where b-locus diversity was important and confirms a negative correlation between e- and b-locus heterozygosity. Trigenic disequilibria corresponded to a significant negative correlation between e- and a-locus heterozygosity due mainly to strong variation among localities within the context of pronounced (digenic) linkage disequilibria. Although substantial, the average increase in a/e-locus single heterozygosity implemented by higher order disequilibria within localities was not significant.
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- Dubiski S., Good P. W., Jr Population genetics of the heavy chain immunoglobulin allotypes in the rabbit. Proc Soc Exp Biol Med. 1972 Nov;141(2):486–489. doi: 10.3181/00379727-141-36804. [DOI] [PubMed] [Google Scholar]
- Friedman M. L., Tunyaplin C., Zhai S. K., Knight K. L. Neonatal VH, D, and JH gene usage in rabbit B lineage cells. J Immunol. 1994 Jan 15;152(2):632–641. [PubMed] [Google Scholar]
- Hamers-Casterman C., Wittouck E., van der Loo W., Hamers R. Phylogeny of the rabbit gamma-chain determinants: a d12-like antigenic determinant in Pronolagus rupestris. J Immunogenet. 1979 Dec;6(6):373–381. doi: 10.1111/j.1744-313x.1979.tb00692.x. [DOI] [PubMed] [Google Scholar]
- Haouas H., el Gaaied A., Cazenave P. A. Genetic polymorphism of rabbit VHa region: a new allotype, a108. Res Immunol. 1989 Mar-Apr;140(3):265–273. doi: 10.1016/0923-2494(89)90059-x. [DOI] [PubMed] [Google Scholar]
- Hardy C., Callou C., Vigne J. D., Casane D., Dennebouy N., Mounolou J. C., Monnerot M. Rabbit mitochondrial DNA diversity from prehistoric to modern times. J Mol Evol. 1995 Mar;40(3):227–237. doi: 10.1007/BF00163228. [DOI] [PubMed] [Google Scholar]
- Hedrick P. W. Evolution at HLA: possible explanations for the deficiency of homozygotes in two populations. Hum Hered. 1990;40(4):213–220. doi: 10.1159/000153933. [DOI] [PubMed] [Google Scholar]
- Herd Z. L., Edmonds J. W. Population genetics of Aa and Ab immunoglobulin allotypes in wild rabbits of south-eastern Australia. I. Allotype frequencies. J Immunogenet. 1977 Oct;4(5):315–323. doi: 10.1111/j.1744-313x.1977.tb00914.x. [DOI] [PubMed] [Google Scholar]
- Howard J. C. Immunology. Disease and evolution. Nature. 1991 Aug 15;352(6336):565–567. doi: 10.1038/352565a0. [DOI] [PubMed] [Google Scholar]
- Hughes A. L., Nei M. Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection. Proc Natl Acad Sci U S A. 1989 Feb;86(3):958–962. doi: 10.1073/pnas.86.3.958. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelus A. S., Gell P. G. Immunoglobulin allotypes of experimental animals. Prog Allergy. 1967;11:141–184. [PubMed] [Google Scholar]
- Kelus A. S., Steinberg C. M. Is there a high rate of mitotic recombination between the loci encoding immunoglobulin VH and CH regions in gonial cells? Immunogenetics. 1991;33(4):255–259. doi: 10.1007/BF00230503. [DOI] [PubMed] [Google Scholar]
- Knight K. L., Becker R. S. Molecular basis of the allelic inheritance of rabbit immunoglobulin VH allotypes: implications for the generation of antibody diversity. Cell. 1990 Mar 23;60(6):963–970. doi: 10.1016/0092-8674(90)90344-e. [DOI] [PubMed] [Google Scholar]
- Lummus Z., Cebra J. J., Mage R. Correspondence of the relative cellular distribution and serum concentration of allelic allotypic markers in normal and "allotype-suppressed" heterozygous rabbits. J Immunol. 1967 Oct;99(4):737–743. [PubMed] [Google Scholar]
- Mage R. G., Dray S., Gilman-Sachs A., Hamers-Casterman C., Hamers R., Hanly W. C., Kindt T. J., Knight K. L., Mandy W. J., Naessens J. Rabbit heavy chain haplotypes--allotypic determinants expressed by VH-CH recombinants. Immunogenetics. 1982 Mar;15(3):287–297. doi: 10.1007/BF00364337. [DOI] [PubMed] [Google Scholar]
- Ritchie K. A., Brinster R. L., Storb U. Allelic exclusion and control of endogenous immunoglobulin gene rearrangement in kappa transgenic mice. Nature. 1984 Dec 6;312(5994):517–520. doi: 10.1038/312517a0. [DOI] [PubMed] [Google Scholar]
- Short J. A., Sethupathi P., Zhai S. K., Knight K. L. VDJ genes in VHa2 allotype-suppressed rabbits. Limited germline VH gene usage and accumulation of somatic mutations in D regions. J Immunol. 1991 Dec 1;147(11):4014–4018. [PubMed] [Google Scholar]
- Takahata N., Satta Y., Klein J. Polymorphism and balancing selection at major histocompatibility complex loci. Genetics. 1992 Apr;130(4):925–938. doi: 10.1093/genetics/130.4.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
- Webb N. J., Ibrahim K. M., Bell D. J., Hewitt G. M. Natal dispersal and genetic structure in a population of the European wild rabbit (Oryctolagus cuniculus). Mol Ecol. 1995 Apr;4(2):239–247. doi: 10.1111/j.1365-294x.1995.tb00213.x. [DOI] [PubMed] [Google Scholar]
- van der Loo W., Arthur C. P., Richardson B. J., Wallage-Drees M., Hamers R. Nonrandom allele associations between unlinked protein loci: are the polymorphisms of the immunoglobulin constant regions adaptive? Proc Natl Acad Sci U S A. 1987 May;84(9):3075–3079. doi: 10.1073/pnas.84.9.3075. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Loo W., Bouton C. E., Sanchez M., Mougel F., Castién E., Hamers R., Monnerot M. Characterization and DNA sequence of the b6w2 allotype of the rabbit immunoglobulin kappa 1 light chain (b locus). Immunogenetics. 1995;42(5):333–341. doi: 10.1007/BF00179394. [DOI] [PubMed] [Google Scholar]
- van der Loo W., Ferrand N., Soriguer R. C. 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. Genetics. 1991 Apr;127(4):789–799. doi: 10.1093/genetics/127.4.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Loo W. 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. Genetics. 1993 Sep;135(1):171–187. doi: 10.1093/genetics/135.1.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Loo W., Verdoodt B. Patterns of interallelic divergence at the rabbit b-locus of the immunoglobulin light chain constant region are in agreement with population genetical evidence for overdominant selection. Genetics. 1992 Dec;132(4):1105–1117. doi: 10.1093/genetics/132.4.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]