EVOLUTIONARY GENETICS OF DNA REPAIR AND RECOMBINATION

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Our general goal is to study the functional relationship between sexual recombination and DNA repair. By studing the relationship of sex to genetic repair, we hope to advance the understanding of what we think are two related problems. First, is the problem of naturally evolved defenses against agents which cause genetic damage and, hence, cancer. Second, is the problem of the evolutionary function of sexual reproduction. The evolution of recombination and sexual reproduction are major unsolved problems in evolutionary biology. The proposed research tests, in Bacillus subtilis, the hypothesis that out-crossing sex increases survivorship because of its role in the repair of DNA damage, and hence that genetic repair provides a selective advantage for sex. Our specific projects are as follows. First we propose testing whether, as the repair hypothesis predicts, the frequency of individuals which are resistant to damaging agents depends upon how sexual the strain is (i.e., the inherent transformability of the strain. Second, we propose testing whether by manipulating the transformability of known strains we can alter the frequency of damage resistant cells in the direction predicted by the repair hypothesis. Third, we propose experiments designed to isolate the sexual cells from the asexual cells and to measure their relative frequencies and survivorships in the presence of varying amounts of DNA damaging agents. Fourth, we propose selection experiments to increase the frequency of sexual recombinational repair by selecting survivors of treatment with DNA damaging agents. Fifth, we propose testing whether sites of sexual recombinational are random or coincident with respect to sites of DNA damage.