Bioinformatic tools for the analysis of microbial genomes

Sammanfattning: High throughput genome sequencing projects are producing an enormous amount of rawdata which has to be converted into biological knowledge. The newly established field ofbioinformatics is concerned with the continuous development of novel methods and toolsfor the comparative analysis of DNA sequences and genomic data.The primary task of bioinformatics in genome sequencing projects is to identify andfunctionally classify all proteins putatively encoded by the genome. Due to the amountof data, first time analyses in large-scale projects have to be rudimentary and fast. We have sequenced Rickettsia prowazekii, an α-proteobacterium and the cauative agent of epidemic typhus in humans. For the analysis of the R. prowazekii genome we have developed CapDB, a sequence analysis and management system for automatic functional gene annotations and graphical display of the genome together with the biological information.Analysis of the 1.111.523 bp R. prowazekii genome revealed 834 complete open read-ing frames of which 523 could be linked to a biological function. In addition, 12 putativepseudogenes and an unusually high proportion of non-coding DNA (24%) were identified.Phylogenetic analyses indicate that R. prowazekii is more closely related to mitochondriathan other microbes studied thus far.With the availability of complete genomes, new ways of comparing organisms haveemerged., To study genomic structures, we have developed tools and methods for geneorder based comparisons (GRS) and complete genome alignments (GOBLIN). We de-fine the complete set of phylogenetic trees derived from the proteome of an organism asthe "phylome" and present software for automatic, large-scale reconstructions of phylo-genetic relationships - thus setting the stage for phylogenomic comparisons of microbialgenomes which are likely to reveal a rich web of evolutionary connections.