| Genome sequences are fundamentally altering biology, finally making global studies possible. Genome-wide experiments have changed perspectives and paradigms. The ability to test all genes in an organism now makes completion (or comprehensiveness) in biology practical. Genome sequences provide new tools for discovery of biological processes and functions. Finally, DNA sequence provides raw material for comparison, which furthers our understanding of evolution.; In this thesis, I have used genome sequences to study Caulobacter crescentus, a model system for cell cycle studies, and other prokaryotes. Two proteins in Caulobacter, the DNA-binding response regulator CtrA and the DNA methyltransferase CcrM, are key cell cycle regulators. With the genome sequence, I have made a complete description of the set of genes regulated by CtrA. This work verifies previous studies and identifies new candidate genes which may act in the regulatory network controlling the Caulobacter cell cycle.; The CcrM DNA methyltransferase is involved in regulating DNA replication initiation and gene transcription, but the mechanisms are poorly understood. In E. coli, regulation by DNA methylation requires sequences surrounding methylation sites; the same may be true in Caulobacter . Using the genome sequence as a tool for discovery, I found four long intergenic repeated sequences, called CIR sequences, associated with CcrM methylation sites. Two of these have a conserved sequence organization. Similar sequences are found associated with CcrM sites in other alpha proteobacteria. Based on conservation of sequence organization, the CIR sequences may mediate cell cycle regulation by DNA methylation.; Understanding the nature and causes of diversity is a primary goal of biology. As evolution operates on DNA, genome sequences are a tremendous resource for studying evolution. The study of codon usage has been important in understanding population genetics and prokaryotic evolution. By comparing the gene sequences of prokaryotic and eukaryotic genomes, we have found that codon usage varies along two dimensions. These two dimensions correlate respectively with organism GC content and optimal growth temperature. Therefore, genome-wide codon usage seems to be set by mutational pressures, while variation in codon usage between genes from the same genome may be due to selective forces. |
