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Science 4 March 2005:
Vol. 307. no. 5714, pp. 1463 - 1465
DOI: 10.1126/science.1107008
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Reports

Extensive DNA Inversions in the B. fragilis Genome Control Variable Gene Expression

Ana M. Cerdeño-Tárraga,1 Sheila Patrick,2* Lisa C. Crossman,1 Garry Blakely,3 Val Abratt,4 Nicola Lennard,1 Ian Poxton,5 Brian Duerden,6 Barbara Harris,1 Mike A. Quail,1 Andrew Barron,1 Louise Clark,1 Craig Corton,1 Jonathan Doggett,1 Matthew T. G. Holden,1 Natasha Larke,1 Alexandra Line,1 Angela Lord,1 Halina Norbertczak,1 Doug Ormond,1 Claire Price,1 Ester Rabbinowitsch,1 John Woodward,1 Bart Barrell,1 Julian Parkhill1*

The obligately anaerobic bacterium Bacteroides fragilis, an opportunistic pathogen and inhabitant of the normal human colonic microbiota, exhibits considerable within-strain phase and antigenic variation of surface components. The complete genome sequence has revealed an unusual breadth (in number and in effect) of DNA inversion events that potentially control expression of many different components, including surface and secreted components, regulatory molecules, and restriction-modification proteins. Invertible promoters of two different types (12 group 1 and 11 group 2) were identified. One group has inversion crossover (fix) sites similar to the hix sites of Salmonella typhimurium. There are also four independent intergenic shufflons that potentially alter the expression and function of varied genes. The composition of the 10 different polysaccharide biosynthesis gene clusters identified (7 with associated invertible promoters) suggests a mechanism of synthesis similar to the O-antigen capsules of Escherichia coli.

1 Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
2 Department of Microbiology and Immunobiology, School of Medicine, Queen's University of Belfast, Grosvenor Road, Belfast, BT12 6BN, UK.
3 Institute of Cell and Molecular Biology, University of Edinburgh, Darwin Building, Kings Buildings, Edinburgh EH9 3JR, UK.
4 Department of Molecular and Cell Biology, University of Cape Town, Private Bag Rondebosch 7701, South Africa.
5 Division of Medical Microbiology, University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, UK.
6 Department of Medical Microbiology, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK.

Note added in proof: The genome sequence of another strain of B. fragilis has recently been published (19), and the analysis is in general agreement with that presented here.

* To whom correspondence should be addressed. E-mail: parkhill{at}sanger.ac.uk (J.P.); s.patrick{at}qub.ac.uk (S.P.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)