No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

The changes seen in DNA sequences at the molecular level suggest that a continuum of mutational effects exists, such that newly arising mutations may be strongly deleterious, weak or neutral in effect or strongly advantageous. The recent crop of fully sequenced microbial genomes provide a rich resource for evolutionary analyses and here we use genome sequences of the enteric bacteria, Escherichia coli and Salmonella enterica to examine molecular evolution in the prokaryotes, finding high levels of adaptive evolution in both species. As there is evidence that slightly deleterious mutations are segregating in both of these species, we tested the assumption that slightly deleterious mutations downwardly bias estimates of adaptive amino acid substitution and look at ways to remove such a bias. We then examined theoretically a model of molecular sequence evolution which allowed some proportion of new mutations to be slightly advantageous and looked for evidence of this using a comparative method. We show that there is some support for a model of molecular evolution that allows slightly advantageous compensatory evolution and that such compensatory evolution may follow an expansion in population size. Finally, we compared intergenic regions from E. coli and Salmonella to look at the patterns of molecular evolution in non-coding DNA from these species.

The human gastric pathogen Helicobacter pylori has been reported to be genetically diverse. However, initial research in this study indicated that the development of resistance to non-therapeutic antibiotics in vitro is comparable in frequency to other species of bacteria. Both spontaneous and induced mutation frequencies were found to be no higher than those observed in Escherichia coli. Conjugation experiments were performed between two type strains of H. pylori; one containing plasmid DNA of a conjugative size and the other being a plasmid-free antibiotic-resistant mutant, developed from earlier mutation studies. Following conjugation and antibiotic selection the isolates were screened for the presence of plasmid DNA. In initial studies, screening for plasmid DNA was performed using a non-radioactively labelled probe derived from plasmid DNA, in connection with Southern blotting / DNA hybridisation experiments. Due to problems with reproducibility, a simpler method was developed, using a PCR specific for H. pylori plasmid DNA, delivering consistent, accurate results. It was shown that conjugation occurred between these two H. pylori strains. Analysis of the 16S rDNA of a number of H. pylori strains was undertaken. Little genetic variation between isolates was observed in this study, using both nucleotide sequence data and restriction digest analysis. In a comparative study, the variation in 16S rDNA sequence observed between H. pylori isolates was found to be no greater than that observed between E.coli isolates. Despite all previous reports of genetic variability within the species, H. pylori did not display high mutation frequencies or a large amount of inherent genetic variability in this study. The discovery of conjugative DNA transfer does, however, suggest one possible mechanism for the generation of genetic variation and transfer of antibiotic resistance between H. pylori strains.