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Intracellular pathogens go extreme: genome evolution in the Rickettsiales
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Molecular Evolution.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Molecular Evolution.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Molecular Evolution.
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2007 (English)In: Trends in Genetics, ISSN 0168-9525, Vol. 23, no 10, 511-520 p.Article, review/survey (Refereed) Published
Abstract [en]

The Rickettsiales, a genetically diverse group of the α-Proteobacteria, include major mammalian pathogens, such as the agents of epidemic typhus, scrub typhus, ehrlichioses and heartwater disease. Sequenced genomes of this bacterial order have provided exciting insights into reductive genome evolution, antigenic variation and host cell manipulation. Recent results suggest that human pathogens emerged relatively late in the evolution of the Rickettsiales. Surprisingly, there is no association between pathogenicity and the acquisition of novel virulence genes. Here, we explore the genomic differences between members of the Rickettsiales and ask what are the changes that enable infectious agents to emerge from seemingly harmless bacteria.

Place, publisher, year, edition, pages
2007. Vol. 23, no 10, 511-520 p.
Keyword [en]
Bacteria, Pathogenicity, Genome, Rickettsiales, Molecular evolution, Intracellular
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96598DOI: 10.1016/j.tig.2007.08.002ISI: 000250636600008PubMedID: 17822801OAI: oai:DiVA.org:uu-96598DiVA: diva2:171231
Available from: 2008-01-10 Created: 2008-01-10 Last updated: 2011-03-29Bibliographically approved
In thesis
1. Methods and Applications in Comparative Bacterial Genomics
Open this publication in new window or tab >>Methods and Applications in Comparative Bacterial Genomics
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Comparative studies of bacterial genomes, now counting in the hundreds, generate massive amounts of information. In order to support a systematic and efficient approach to genomic analyses, a database driven system with graphic visualization of genomic properties was developed - GenComp. The software was applied to studies of obligate intracellular bacteria. In all studies, ORFs were extracted and grouped into ORF-families. Based on gene order synteny, orthologous clusters of core genes and variable spacer ORFs were identified and extracted for alignments and computation of substitution frequencies.

The software was applied to the genomes of six Chlamydia trachomatis strains to identify the most rapidly evolving genes. Five genes were chosen for genotyping, and close to a 3-fold higher discrimination capacity was achieved than that of serotypes.

With GenComp as the backbone, a massive comparative analysis were performed on the variable gene set in the Rickettsiaceae, which includes Rickettsia prowazekii and Orientia tsutsugamushi, the agents of epidemic and scrub typhus, respectively. O. tsutsugamushi has the most exceptional bacterial genome identified to date; the 2.2 Mb genome is 200-fold more repeated than the 1.1 Mb R. prowazekii genome due to an extensive proliferation of conjugative type IV secretion systems and associated genes. GenComp identified 688 core genes that are conserved across 7 closely related Rickettsia genomes along with a set of 469 variably present genes with homologs in other species. The analysis indicates that up to 70% of the extensively degraded and variably present genes represent mobile genetic elements and genes putatively acquired by horizontal gene transfer. This explains the paradox of the high pseudogene load in the small Rickettsia genomes. This study demonstrates that GenComp provides an efficient system for pseudogene identification and may help distinguish genes from spurious ORFs in the many pan-genome sequencing projects going on worldwide.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 66 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 381
Keyword
Biology, Biologi
Identifiers
urn:nbn:se:uu:diva-8398 (URN)978-91-554-7061-6 (ISBN)
Public defence
2008-02-01, Zootissalen, Evolutionsmusset, Villavägen 9, Uppsala, 10:00 (English)
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Available from: 2008-01-10 Created: 2008-01-10 Last updated: 2010-03-16Bibliographically approved

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Fuxelius, Hans-HenrikWestberg, JoakimAndersson, Siv G.E.

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