Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains
| Autor: | Steven L. Salzberg, Robert T. DeBoy, Hoda Khouri, William R. Jacobs, L. Carpenter, T. Utterback, Maria D. Ermolaeva, Owen White, Jonathan A. Eisen, J. C. Venter, Lowell Umayam, Robert J. Dodson, Erin Hickey, William R. Bishai, Arthur L. Delcher, Daniel H. Haft, Janice Weidman, Robert D. Fleischmann, A. Mikula, John Gill, Jeremy Peterson, William C. Nelson, David Alland, Michelle L. Gwinn, James F. Kolonay, Claire M. Fraser |
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| Rok vydání: | 2002 |
| Předmět: |
Nonsynonymous substitution
Molecular Sequence Data Virulence Biology Microbiology Genome Polymorphism Single Nucleotide Mycobacterium tuberculosis Evolution Molecular Bacterial Proteins Genetic variation Gene family Humans Tuberculosis Genetic variability Molecular Biology Gene Phylogeny Genetics Polymorphism Genetic Genetic Variation Sequence Analysis DNA biology.organism_classification Sequence Alignment Genome Bacterial Population Genetics and Evolution |
| Zdroj: | ResearcherID |
| ISSN: | 0021-9193 |
| Popis: | Virulence and immunity are poorly understood inMycobacterium tuberculosis.We sequenced the complete genome of theM. tuberculosisclinical strain CDC1551 and performed a whole-genome comparison with the laboratory strain H37Rv in order to identify polymorphic sequences with potential relevance to disease pathogenesis, immunity, and evolution. We found large-sequence and single-nucleotide polymorphisms in numerous genes. Polymorphic loci included a phospholipase C, a membrane lipoprotein, members of an adenylate cyclase gene family, and members of the PE/PPE gene family, some of which have been implicated in virulence or the host immune response. Several gene families, including the PE/PPE gene family, also had significantly higher synonymous and nonsynonymous substitution frequencies compared to the genome as a whole. We tested a large sample ofM. tuberculosisclinical isolates for a subset of the large-sequence and single-nucleotide polymorphisms and found widespread genetic variability at many of these loci. We performed phylogenetic and epidemiological analysis to investigate the evolutionary relationships among isolates and the origins of specific polymorphic loci. A number of these polymorphisms appear to have occurred multiple times as independent events, suggesting that these changes may be under selective pressure. Together, these results demonstrate that polymorphisms amongM. tuberculosisstrains are more extensive than initially anticipated, and genetic variation may have an important role in disease pathogenesis and immunity. |
| Databáze: | OpenAIRE |
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