The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host–cell interaction genes

doi:10.1073/pnas.0611553104

The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host–cell interaction genes

*Department of Microbiology and Immunology and
^§Seoul National University Biomedical Informatics, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Republic of Korea;
^†GenoTech Corporation 59-5 Jang-Dong, Yuseong-Gu, Daejeon 305-343, Republic of Korea;
^‡Program of Molecular Evolution, Department of Evolution, Genomics and Systematics, Evolutionary Biology Center, Uppsala University, Norbyvägen 18C, 772 36 Uppsala, Sweden;
^¶Supercomputing Center, Korea Institute of Science and Technology Information, 52-11 Eoeun-dong, Yuseong, Daejeon 305-806, Republic of Korea;
^‖Department of Microbiology, Cheju National University College of Medicine, Cheju 690-756, Republic of Korea; and
**Department of Microbiology, Konkuk University College of Medicine, Choongju-si, Chungbuk 380-701, Republic of Korea

Edited by Nancy A. Moran, University of Arizona, Tucson, AZ, and approved March 19, 2007 (received for review December 26, 2006)

Abstract

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.

Footnotes

^††To whom correspondence should be addressed. E-mail: molecule{at}plaza.snu.ac.kr
Author contributions: N.-H.C., S.G.E.A., M.-S.C., and I.-S.K. designed research; H.-R.K., J.-H.L., Se-Yoon Kim, Jaejong Kim, S.C., Sang-Yoon Kim, J.H.K., Jihun Kim, S.J.L., Y.-S.K., W.-J.J., K.-H.P., and M.-S.C. performed research; H.-H.F. contributed new reagents/analytic tools; N.-H.C., A.C.D., H.-H.F., J.Y., and S.G.E.A. analyzed data; and N.-H.C., S.G.E.A., and I.-S.K. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The sequence reported in this paper has been deposited in the European Molecular Biology database (accession no. AM494475).
This article contains supporting information online at www.pnas.org/cgi/content/full/0611553104/DC1.
Abbreviations:

TFSS,

type IV secretion system;

HK,

histidine kinase.