RECRUITMENT OF MULTIPLE ALLELES WITHIN THE EB RECOMBINATIONAL HOTSPOTIN MURINE MHC

Genetic recombination has been proposed to have played a major role in generating the extensive polymorphism that distinguishes the genes of the major histocompatibility complex (MHC). The proximal region of th e murine H-2 represents a unique segment of DNA encompassing at least four hotspots for meiotic recombination. One of these hotspots lies wi thin the second intron of the class II Eb gene and has been defined at the nucleotide level for a number of simple two-allele crosses. In th is report we studied two crosses in which one or both parents in thems elves were H2Eb recombinants and three alleles were present within the hotspots of each pair of the parental haplotypes. Nucleotide analysis indicated that the break points in these secondary recombinants, like those in the primary recombinants, were also discrete and clustered w ithin the H2Eb second intron. Thus, in one instance two and in the oth er instance three alleles were present within the hotspots of these re combinants. These observations strongly suggest that meiotic recombina tion could be an important mechanism contributing to MHC polymorphism.