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The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host–cell interaction genes
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2007 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 104, no 19, 7981-7986 p.Article in journal (Refereed) Published
Abstract [en]

Scrub typhus is caused by the obligate intracellular rickettsia Orientia tsutsugamushi (previously called Rickettsia tsutsugamushi). The bacterium is maternally inherited in trombicuid mites and transmitted to humans by feeding larvae. We report here the 2,127,051-bp genome of the Boryong strain, which represents the most highly repeated bacterial genome sequenced to date. The repeat density of the scrub typhus pathogen is 200-fold higher than that of its close relative Rickettsia prowazekii, the agent of epidemic typhus. A total of 359 tra genes for components of conjugative type IV secretion systems were identified at 79 sites in the genome. Associated with these are >200 genes for signaling and host–cell interaction proteins, such as histidine kinases, ankyrin-repeat proteins, and tetratrico peptide-repeat proteins. Additionally, the O. tsutsugamushi genome contains >400 transposases, 60 phage integrases, and 70 reverse transcriptases. Deletions and rearrangements have yielded unique gene combinations as well as frequent pseudogenization in the tra clusters. A comparative analysis of the tra clusters within the genome and across strains indicates sequence homogenization by gene conversion, whereas complexity, diversity, and pseudogenization are acquired by duplications, deletions, and transposon integrations into the amplified segments. The results suggest intragenomic duplications or multiple integrations of a massively proliferating conjugative transfer system. Diversifying selection on host–cell interaction genes along with repeated population bottlenecks may drive rare genome variants to fixation, thereby short-circuiting selection for low complexity in bacterial genomes.

Place, publisher, year, edition, pages
2007. Vol. 104, no 19, 7981-7986 p.
Keyword [en]
Bacterial genome, Duplication, Repeats
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-14984DOI: 10.1073/pnas.0611553104ISI: 000246461500046PubMedID: 17483455OAI: oai:DiVA.org:uu-14984DiVA: diva2:42755
Available from: 2008-02-01 Created: 2008-02-01 Last updated: 2011-01-31Bibliographically 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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 381
Biology, Biologi
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)
Available from: 2008-01-10 Created: 2008-01-10 Last updated: 2010-03-16Bibliographically approved

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Fuxelius, Hans-HenrikAndersson, Siv
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