EVOLUTIONARY GENETICS OF DNA REPAIR AND RECOMBINATION

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.