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.

Abstract

Population studies at the b-locus of the "constant" regions of the rabbit immunoglobulin kappa 1 light chain (c kappa 1) revealed patterns of gene diversity resembling those that mark the peculiar nature of the major histocompatibility complex, such as large number of alleles, high heterozygosity levels, consistent excess of heterozygous individuals and long allele coalescence times. This paper documents the evolutionary patterns at the b-locus as inferred from DNA sequence comparisons. Among alleles, synonymous substitutions outnumbered expectations for neutral alleles by an order of magnitude. They were distributed randomly throughout the c kappa 1 coding region while interallelic amino acid differences did cluster into segments overlapping with the regions exposed to the solvent. Within these regions, acceptance rates of mutation at amino acid replacement sites were even higher than those at synonymous sites (dr/ds = 1.6-3.0), while in the intervals between these regions the opposite was found (dr/ds approximately 0.3). Under the assumption that allelic variation is adaptive at the molecular surface, the divergence patterns at the b-locus are therefore very similar to those reported for the major histocompatibility complex. An analysis at the quasi silent bas-locus (c kappa 2), which is linked to the b-locus, and comparisons among genes of the "variable" region of the kappa 1 light chains (v kappa 1), revealed patterns of divergence which differed markedly from those observed at the c kappa 1 constant regions. It is suggested that allelic variability at immunoglobulin constant regions can be due to mechanisms similar to those enhancing diversity at histocompatibility loci.

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.

“…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). According to NEI and coworkers, such patterns constitute evidence for overdominant selection NEI 1988, 1989; TAKAHATA, SATTA and KLEIN 1992).…”