Evolution of DNA repair genes, proteins and processes

Abstract

Genomic integrity is under nearly constant threat in all species. The primary mechanism by which organisms maintain their genomic integrity in the face of such threats is through DNA repair. In this thesis I discuss the interface between evolution and DNA repair. First, I discuss the use of comparative studies of repair genes and processes to study evolution. Specifically I discuss the development of the RecA gene as a model molecule for molecular systematic studies of bacteria. Then I discuss how differences in repair can drive evolution by discussing how differences in mismatch repair lead to variation in mutation rates and patterns at microsatellite loci. In the third section, I discuss how evolutionary studies can benefit our understanding of repair both in regard to structure-function studies (of the RecA protein) and in regard to studying diverse multigene families (in this case, the SNF2 family). Finally, in the last main section, I discuss my development of what I refer to as phylogenomics which combines evolutionary reconstructions and genome sequence studies into one composite analysis. The main reason I have developed the phylogenomic approach is that evolutionary studies can improve our understanding of genome sequences and genome sequences can improve inferences of evolutionary history so there is a feedback loop between the two types of study. In addition, I also present some additional results in Appendices regarding DNA turnover in E. coli, DNA repair in the extremely halophilic Archaea, and additional studies of the evolution of RecA.