The roles of mutational and recombinational processess in the diversification of the exon encoding the antigen inding site in the murine major histocompatibility complex II gene Ab were assessed by phylogenetic analysis of allelic nucleotide sequences. A total of 46 alleles of Ab exon 2 from 12 lus species or subspecies and 2 Rattus species were sequenced lar amplification by the polymerase chain reaction. Reliable allec genealogies could not be determined by phylogenetic analyses, due to extensive homoplasy in the data set. This immunoplasy results from the shuffling of polymorphisms beaca alleles by recombinational processes, indicating that polymorphisms in the antigen binding site encoded by Ab are generated by a combination of two processes. First, the accumulation of point mutations has produced highly divergent polymorphic sequence motifs in five regions of Ab exon 2, each coding a portion of the binding site. Some of these motifs MM persisted as polymorphisms in rodents since before the divergence of mouse and rat (>10 million years ago). The cand process mediating Ab diversification involves the shufing of these polymorphic sequence motifs into numerous llic combinations by repeated intraexonic recombination. ile-specific hyperrecombinational mechanisms are not induced in this process within the exon. We postulate that these mechanisms continuously generate new Ab alleles with highly divergent binding sites from which alleles with advantageous antigenuea-binding properties are selectively maintained by some rum of balancing selection.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 1991|
- Ancestral polymorphism
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