FACTORS AFFECTING ECTOPIC GENE CONVERSION IN MICE

Duplicated genes and repetitive sequences are distributed throughout t he genomes of complex organisms. The homology between related sequence s can promote nonalletic (ectopic) recombination, including gene conve rsion and reciprocal exchange. Resolution of these events can result i n translocations, deletions, or other harmful rearrangements. In yeast , ectopic recombination between sequences on nonhomologous chromosomes occurs at high frequency. Because the mammalian genome is replete wit h duplicated sequences and repetitive elements, high levels of ectopic exchange would cause aneuploidy and genome instability. To understand the factors regulating ectopic recombination in mice, we evaluated th e effects of homology length on gene conversion between unlinked seque nces in the male germline. Previously, we found high levels of gene co nversion between lacZ transgenes containing 2557 bp of homology. We re port here that genetic background can play a major role in ectopic rec ombination; frequency of gene conversion was reduced by more than an o rder of magnitude by transferring the transgenes from a CF1 strain bac kground to C57BL/6J. Additionally, conversion rates decreased as the h omology length decreased. Sequences sharing 1214 bp of sequence identi ty underwent ectopic conversion less frequently than a pair sharing 25 57 bp of identity, while 624 bp was insufficient to catalyze gene conv ersion at significant levels. These results suggest that the germline recombination machinery in mammals has evolved in a way that prevents high levels of ectopic recombination between smaller classes of repeti tive sequences, such as the Alu family. Additionally, genomic location appeared to influence the availability of sequences for ectopic recom bination.