EVOLUTIONARY GENETICS OF DNA REPAIR AND RECOMBINATION

我们的总体目标是研究性与性之间的功能关系 重组和DNA修复。通过研究性与性别之间的关系 基因修复，我们希望推进对我们认为是什么的理解 两个相关的问题。首先，是自然进化防御系统的问题 对抗会导致基因损伤，从而导致癌症的药物。第二，是 有性繁殖的进化功能问题。这个 重组和有性繁殖的进化是主要悬而未决的问题 进化生物学中的问题。拟议的研究测试，在芽孢杆菌 枯草杆菌，异交性交提高存活率的假说 因为它在DNA损伤修复中的作用，因此基因 修复为性行为提供了一种选择性优势。 我们的具体项目如下。首先，我们建议测试是否，作为 修复假说预测， 对破坏性物质的抵抗力取决于菌株的性别(即， 应变的内在变化性。第二，我们建议测试 无论是通过操纵已知菌株的可变换性，我们可以改变 所预测的方向上的抗损伤单元的频率 修复假说。第三，我们提出了实验，旨在分离出 从无性细胞中分离出性细胞并测量其亲缘关系 不同数量DNA存在时的频率和存活率 破坏性因素。第四，我们提出了选择实验，以增加 通过选择幸存者进行有性重组修复的频率 用DNA损伤剂进行治疗。第五，我们建议测试是否 有性重组的地点是随机的或重合的 DNA损伤的部位。

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.