Sequence conditions for gene conversion of mouse MHC genes

Abstract

We have developed a semi-nested PCR assay which measures gene conversion in mouse MHC class genes. Detectable frequencies occur in DNA from sperm, but not in somatic DNA, such as liver or fibroblast DNA. The frequency of gene conversion events in MHC class II genes varies strongly from one MHC haplotype to another, with the highest detected frequencies as high as 1/40 000 for an individual heterozygous for both donor and acceptor sequences. Deletions or insertions in one gene relative to the other seem to lower the efficiency of gene conversion considerably. However, not all the variation in gene conversion frequency can be readily ascribed to the MHC genes themselves, implying that variation in the non-MHC background genes also might be of importance. Stretches within MHC genes amenable to gene conversion are located in CpG clusters, whereas MHC genes not involved in gene conversion have background CpG levels. This feature extends to some, but not all, of the non-MHC genes that have been reported to undergo gene conversion in mammals. DNA damage, either chemical or radiation-induced, increases the frequency of gene conversion of MHC class 11 genes in cultured cells of the fibroblastoid lineage. The effect of chemical DNA damage seems roughly dose-dependent, whereas irradiation has maximal effect at low doses.