Computer Science Research Works

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    Serendipitous discovery of Wolbachia genomes in multiple Drosophila species
    (Genome Biology, 2005) Salzberg, Steven L.; Dunning Hotopp, Julie C.; Delcher, Arthur L.; Pop, Mihai; Smith, Douglas R; Eisen, Michael B.; Nelson, William C.
    Background: The Trace Archive is a repository for the raw, unanalyzed data generated by largescale genome sequencing projects. The existence of this data offers scientists the possibility of discovering additional genomic sequences beyond those originally sequenced. In particular, if the source DNA for a sequencing project came from a species that was colonized by another organism, then the project may yield substantial amounts of genomic DNA, including near-complete genomes, from the symbiotic or parasitic organism. Results: By searching the publicly available repository of DNA sequencing trace data, we discovered three new species of the bacterial endosymbiont Wolbachia pipientis in three different species of fruit fly: Drosophila ananassae, D. simulans, and D. mojavensis. We extracted all sequences with partial matches to a previously sequenced Wolbachia strain and assembled those sequences using customized software. For one of the three new species, the data recovered were sufficient to produce an assembly that covers more than 95% of the genome; for a second species the data produce the equivalent of a 'light shotgun' sampling of the genome, covering an estimated 75-80% of the genome; and for the third species the data cover approximately 6-7% of the genome. Conclusions: The results of this study reveal an unexpected benefit of depositing raw data in a central genome sequence repository: new species can be discovered within this data. The differences between these three new Wolbachia genomes and the previously sequenced strain revealed numerous rearrangements and insertions within each lineage and hundreds of novel genes. The three new genomes, with annotation, have been deposited in GenBank.
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    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, Eduardo
    The 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.