Gene conversion of major histocompatibility complex genes is associated with CpG-rich regions

We examined 32 DNA sequences of mouse and human major histocompatibility co mplex (MHC) genes believed to have been subjected to gene conversion events . All regions of the mouse H2 genes as well as the human HLA genes which ha ve been implied to be involved in gene conversion events had elevated level s of CpG dinucleotides. whereas the rest of the genes showed extensive CpG suppression. Mouse MHC genes which have been suspected but not directly imp lied to be involved in gene conversion events also showed elevated levels o f CpG dinucleotides, Moreover, both mouse and human MHC genes which have ne ver been suspected of undergoing gene conversion had low levels of CpG thro ughout the genes. These results indicate that high CpG levels are correlate d with gene conversion rather than with polymorphism, as non-polymorphic ge nes that have been implicated as gene conversion donors also have elevated levels of CpG dimers in the involved regions, whereas polymorphic genes whi ch have never been considered to undergo gene conversion events have a low level of CpG dinucleotides. We also studied the methylation pattern of CpG dimers in the Abk gene by restriction enzyme digestion of mouse testis DNA followed by Southern blot and hybridization to an Abk-specific probe. The e xamined CpG dimers in prepubescent mice, where the latest germline stages a re spermatogonia, leptene, or pachytene, are respectively non-methylated. A ccordingly, the CpG dimers appear to be non-methylated in germline DNA from the testis of prepubescent mice, where gene conversions have been reported to occur.