GENE CONVERSION IN MICE

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The goals of the proposed research are to investigate the frequency, properties, and factors which affect meiotic and mitotic gene conversion in the germline of mice. Gene conversion is the non-reciprocal recombination of genetic information. One manifestation of this process is non-Mendelian segregation of alleles. The result can have profound effects upon genome evolution and diversification. The frequency and mechanism of meiotic gene conversion has been extensively studied in fungi, where one can obtain and score all the products of a single meiosis. Similar experiments are not feasible in mammals. In fact, evidence that meiotic gene conversion actually occurs in mammals is circumstantial. The experiments described in this proposal circumvent the technical and logistical problems which have heretofore limited the study of mammalian gene conversion: generating large numbers of progeny and simple detection of a conversion event. We have designed and tested a system to score populations of murine male gametes for contrived conversion events. The occurrence of a planned event results in correction of a mutated reporter gene and synthesis of histochemically detectable reporter activity in spermatids. Modifications of this strategy will allow a quantitative analysis of both meiotic and mitotic intra- and interchromosomal gene conversion in the germ line. In addition, we intend to investigate the size of gene conversions and the influence of gene structure parameters upon the frequency of these processes. Gene duplication is a central process for evolutionary change and adaptation. Gene conversion significantly influences gene families created through duplication. These experiments will be instrumental for assessing the evolutionary and functional ramifications of gene conversion upon the divergence of related genes.