Computer Science Research Works
Permanent URI for this collectionhttp://hdl.handle.net/1903/1593
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Item Evidence for symmetric chromosomal inversions around the replication origin in bacteria(Genome Biology, 2000-12-04) Eisen, Jonathan A.; Heidelberg, John F.; White, Owen; Salzberg, Steven L.Background: Whole-genome comparisons can provide great insight into many aspects of biology. Until recently, however, comparisons were mainly possible only between distantly related species. Complete genome sequences are now becoming available from multiple sets of closely related strains or species. Results: By comparing the recently completed genome sequences of Vibrio cholerae, Streptococcus pneumoniae and Mycobacterium tuberculosis to those of closely related species - Escherichia coli, Streptococcus pyogenes and Mycobacterium leprae, respectively - we have identified an unusual and previously unobserved feature of bacterial genome structure. Scatterplots of the conserved sequences (both DNA and protein) between each pair of species produce a distinct X-shaped pattern, which we call an X-alignment. The key feature of these alignments is that they have symmetry around the replication origin and terminus; that is, the distance of a particular conserved feature (DNA or protein) from the replication origin (or terminus) is conserved between closely related pairs of species. Statistically significant X-alignments are also found within some genomes, indicating that there is symmetry about the replication origin for paralogous features as well. Conclusions: The most likely mechanism of generation of X-alignments involves large chromosomal inversions that reverse the genomic sequence symmetrically around the origin of replication. The finding of these X-alignments between many pairs of species suggests that chromosomal inversions around the origin are a common feature of bacterial genome evolution.Item Genomic Insights into Methanotrophy: The Complete Genome Sequence of Methylococcus capsulatus (Bath)(PLoS Biology, 2004-10) Ward, Naomi; Larsen, Øivind; Sakwa, James; Bruseth, Live; Khouri, Hoda; Durkin, A. Scott; Dimitrov, George; Jiang, Lingxia; Scanlan, David; Kang, Katherine H.; Lewis, Matt; Nelson, Karen E.; Methe´, Barbara; Wu, Martin; Heidelberg, John F.; Paulsen, Ian T.; Fouts, Derrick; Ravel, Jacques; Tettelin, Herve; Ren, Qinghu; Read, Tim; DeBoy, Robert T.; Seshadri, Rekha; Salzberg, Steven L.; Jensen, Harold B.; Birkeland, Nils Kare; Nelson, William C.; Dodson, Robert J.; Grindhaug, Svenn H.; Holt, Ingeborg; Eidhammer, Ingvar; Jonasen, Inge; Vanaken, Susan; Utterback, Terry; Feldblyum, Tamara V.; Fraser, Claire M.; Lillehaug, Johan R.; Eisen, Jonathan A.Methanotrophs are ubiquitous bacteria that can use the greenhouse gas methane as a sole carbon and energy source for growth, thus playing major roles in global carbon cycles, and in particular, substantially reducing emissions of biologically generated methane to the atmosphere. Despite their importance, and in contrast to organisms that play roles in other major parts of the carbon cycle such as photosynthesis, no genome-level studies have been published on the biology of methanotrophs. We report the first complete genome sequence to our knowledge from an obligate methanotroph, Methylococcus capsulatus (Bath), obtained by the shotgun sequencing approach. Analysis revealed a 3.3-Mb genome highly specialized for a methanotrophic lifestyle, including redundant pathways predicted to be involved in methanotrophy and duplicated genes for essential enzymes such as the methane monooxygenases. We used phylogenomic analysis, gene order information, and comparative analysis with the partially sequenced methylotroph Methylobacterium extorquens to detect genes of unknown function likely to be involved in methanotrophy and methylotrophy. Genome analysis suggests the ability of M. capsulatus to scavenge copper (including a previously unreported nonribosomal peptide synthetase) and to use copper in regulation of methanotrophy, but the exact regulatory mechanisms remain unclear. One of the most surprising outcomes of the project is evidence suggesting the existence of previously unsuspected metabolic flexibility in M. capsulatus, including an ability to grow on sugars, oxidize chemolithotrophic hydrogen and sulfur, and live under reduced oxygen tension, all of which have implications for methanotroph ecology. The availability of the complete genome of M. capsulatus (Bath) deepens our understanding of methanotroph biology and its relationship to global carbon cycles. We have gained evidence for greater metabolic flexibility than was previously known, and for genetic components that may have biotechnological potential.Item Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a Model Eukaryote(PLoS Biology, 2006) Eisen, Jonathan A.; Coyne, Robert S.; Wu, Martin; Wu, Dongying; Thiagarajan, Mathangi; Wortman, Jennifer R.; Badger, Jonathan H.; Ren, Qinghu; Amedeo, Paolo; Jones, Kristie M.; Tallon, Luke J.; Delcher, Arthur L.; Salzberg, Steven L.; Silva, Joana C.; Haas, Brian J.; Majoros, William H.; Farzad, Maryam; Carlton, Jane M.; Smith, Robert K. Jr.; Garg, Jyoti; Pearlman, Ronald E.; Karrer, Kathleen M.; Sun, Lei; Manning, Gerard; Elde, Nels C.; Turkewitz, Aaron P.; Asai, David J.; Wilkes, David E.; Wang, Yufeng; Cai, Hong; Collins, Kathleen; Stewart, B. Andrew; Lee, Suzanne R.; Wilamowsk, Katarzyna; Weinberg, Zasha; Ruzzo, Walter L.; Wloga, Dorota; Gaertig, Jacek; Frankel, Joseph; Tsao, Che-Chia; Gorovsky, Martin A.; Keeling, Patrick J.; Waller, Ross F.; Patron, Nicola J.; Cherry, J. Michael; Stover, Nicholas A.; Krieger, Cynthia J.; del Toro, Christina; Ryder, Hilary F.; Williamson, Sondra C.; Barbeau, Rebecca A.; Hamilton, Eileen P.; Orias, EduardoThe ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model organisms makes T. thermophila an ideal model for functional genomic studies to address biological, biomedical, and biotechnological questions of fundamental importance.