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Comparative Analysis Of Mobile Genome In The Model Strains Of Streptomyces

Posted on:2012-02-13Degree:MasterType:Thesis
Country:ChinaCandidate:Y C ShaoFull Text:PDF
GTID:2120330338984317Subject:Microbiology
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Bioinformatics- and microarray-facilitated comparative analyses have revealed that some bacterial species possess extremely plastic genomes. In this study we have developed mGenomeSubtractor to perform highly-parallel genome-scale in silico'subtractive hybridization'analyses of reference genomes against up to forty comparator genomes simultaneously. This mpiBLAST-based tool allows rapid alignment of tens of NCBI-archived or user-supplied genome sequences in under a minute. Recently we have used the PC-cluster-host mGenomeSubtractor to investigate genomic mosaicism and examine core/accessory regions of the sequenced Streptomyces coelicolor and Streptomyces lividans genomes.The soil-inhabiting Streptomyces are characterized by large linear chromosomes (7– 11 Mb), high G+C content and high degree of genetic instability. Using mGenomeSubtractor-facilitated in silico CGH of S. lividans TK24 against S. coelicolor A3(2), only 472 unique CDS out of all 7,751 annotated S. lividans TK2 CDS were identified (Blastn-based H-values < 0.81) as strain-specific. Following merging of identified contiguous strain-specific CDS, the 8.6 Mb S. lividans TK24 linear chromosome was found to have 597 kb of strain-specific accessory regions containing nine large IGs carrying more than 10 CDS, offering significant potential for the fine-tuning of traits and/or for S. lividans TK24-specific adaptations. Based on these data we screened the collected Streptomyces strains by PCR for eight large S. lividans islands identified; our results demonstrated the likely presence of these islands in a second S. lividans strain 66 and its absence in other Streptomyces species. Similarly, using in silico CGH of S. coelicolor A3(2) against S. lividans TK24, 14 large S. coelicolor A3(2) accessory genomic regions were identified. The Dnd DNA degradation phenotype was firstly observed during normal and pulsed-field gel electrophoresis of genomic DNA from Streptomyces lividans 66, which is governed by the five-gene dnd cluster within a genomic island. Intriguingly, to date all identified dnd clusters lie within mobile genetic elements, the vast majority in laterally transferred genomic islands. In this study, we have developed an dndDB database. It organizes details of 32 syntenic dnd clusters from 30 species of Eubacteria and Archaea, 31 dnd-bearing genomic islands and one plasmid containing 140 dnd genes, and 397 other genes coding for proteins with varying levels of similarity to Dnd proteins. A broad range of similarity search, sequence alignment and phylogenetic tools are readily accessible to allow for to individualized directions of research focused on dnd genes.Interestingly, some dnd islands carrying toxin-antitoxin locus. Two-gene and much less frequently three-gene Type 2 TA loci code for cognate partners that have been hypothesized or demonstrated to play key roles in stress response, bacterial physiology and stabilization of horizontally acquired genetic elements. In this study, we have develop an integrated database, named TADB, that provides comprehensive information about Type 2 toxin-antitoxin loci, genetic features that are richly distributed throughout bacterial and archaeal genomes. TADB offers a unique compilation of both predicted and experimentally supported Type 2 TA loci-relevant data and currently contains 10,753 Type 2 TA gene pairs identified within 1,240 prokaryotic genomes, and details of over 260 directly relevant scientific publications. A broad range of similarity search, sequence alignment, genome context browser and phylogenetic tools are readily accessible via TADB.We propose that a platform such as proposed in this study will support the rapidly escalating number of comparative bacterial genomics studies aimed at defining genomic biomarkers of evolutionary lineage, phenotype, pathotype, environmental adaptation and/or disease-association of diverse bacterial species.
Keywords/Search Tags:Streptomyces coelicolor, Streptomyces lividans, genomic island, DNA phosphorothioation, Type 2 toxin-antitoxin system
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