Exploration of Microbial Genomic Sequences via Comparative Analysis

94 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1999.This work presents three new applications of comparative sequence analysis. (1) CRITICA (Coding Region Identification Tool Invoking Comparative Analysis) is a suite of programs for identifying likely protein coding sequences in prokaryotic DNA by combining comparative analysis of DNA sequences with more common noncomparative methods. In the comparative component of the analysis, regions of DNA are aligned with related sequences from the DNA databases; if the translation of the aligned sequences has greater amino acid identity than expected for the observed percentage nucleotide identity, this is interpreted as evidence for coding. CRITICA also incorporates noncomparative information in the form of dicodon bias. The dicodon bias information is derived by iterative analysis of the data so that CRITICA is not dependent upon the existence or accuracy of coding sequence annotations in the databases and hence is well suited for the analysis of novel genomes. CRITICA was tested by analyzing the available Salmonella typhimurium DNA sequences and proved to be more accurate than GenMark. (2) The complete genome of Methanococcus jannaschii, combined with sequence data from its mesophilic relatives, is an excellent resource for the study of thermostability. 115 complete and partial protein sequences from the mesophilic relatives were aligned to M. jannaschii sequence and the differences were noted. Compared to their homologs in its mesophilic relatives, M. jannaschii proteins are more hydrophobic, contain more charged residues, have a higher average residue volume, and have fewer uncharged polar residues. (3) Codon usage varies both between organisms and between different genes in the same organism. This observation has been used as the basis for earlier work in identifying highly expressed and horizontally transferred genes in Escherichia coli. The complete genomes of Escherichia coli , Methanococcus jannaschii, Archaeoglobus fulgidus, Methanobacterium thermoautotrophicum, Pyrococcus horikoshii and Aquifex aeolicus were analyzed for evidence of highly expressed and horizontally transferred genes. The apparent percentage of horizontally transferred genes in the analyzed genomes ranges from 0--14%, and the apparent percentage of highly expressed genes ranges from 0--11 %.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD