Study of metabolic adaptation using bioinformatics approaches

Evolutionary analysis of a wide spectrum of phylogenetically diverse organisms is essential for the understanding of adaptive strategies utilized by organisms inhabiting different environments. Common ancestry of eukaryotes, prokaryotes and archaea lead to similarity of many molecular functions. On the other hand, differences in organisms' structural complexity, physiology, and lifestyle result in the emergence of variations of molecular function, metabolic organization and phenotypic features. Identification of similarities and variations in enzymes are important for studies of thermostable enzymes of interest to biotechnology. In addition, the variations of enzymes for particular taxonomic groups are of interest to biomedical, bioremediation and biodefense research.;In the course of my Ph.D. work I have developed Chisel---an integrated bioinformatics environment and clustering algorithm for identification and characterization of taxonomic and evolutionary variations of enzymatic proteins. Analysis of enzymatic sequences using the Chisel environment provided the basis for reasoning about the adaptation history of a set of enzymatic functions.;The need for such a system was confirmed through Chisel's successful use by a number of scientific applications, including the Great Lakes Regional Center of Excellence (GLACE) for Biodefense and Emerging infections; the Midwest Center for Structural Genomics for characterization of bacterial pathogens; the Shewanella Federation and Thermotoga Federation in the framework of the DOE Microbial genomes program; the Allegheny-Singer Research Institute for evolutionary analysis of Haemophilus; Northern Illinois University; PNNL for analysis of Hanford site metagenomes and many others.;Such projects include, the analysis of 10 Shewanella strains using the Chisel clusters to reconstruct metabolic pathways. In the process, I was able to identify several enzymes in key metabolic pathways whose signatures were acquired via horizontal gene transfer. Additionally, the Chisel protein families aided the interpretation of fragments in metagenomes for characterization of function and phylogenetic affiliation, thus providing new methods for identification of organisms in an environment.