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Letters to Nature
Nature 431, 476-481 (23 September 2004) | doi:10.1038/nature02833; Received 24 March 2004; Accepted 12 July 2004
Tropism switching in Bordetella bacteriophage defines a family of diversity-generating retroelements
Sergei Doulatov1,4, Asher Hodes1,4, Lixin Dai3, Neeraj Mandhana1, Minghsun Liu1, Rajendar Deora1, Robert W. Simons1,2, Steven Zimmerly3 & Jeff F. Miller1,2
- Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA
- The Molecular Biology Institute, University of California, Los Angeles, California 90095, USA
- Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada
- These authors contributed equally to this work
Correspondence to: Jeff F. Miller1,2 Email: jfmiller@ucla.edu
Abstract
Bordetella bacteriophages generate diversity in a gene that specifies host tropism1. This microevolutionary adaptation is produced by a genetic element that combines the basic retroelement life cycle of transcription, reverse transcription and integration with site-directed, adenine-specific mutagenesis. Central to this process is a reverse transcriptase-mediated exchange between two repeats; one serving as a donor template (TR) and the other as a recipient of variable sequence information (VR)1. Here we describe the genetic basis for diversity generation. The directionality of information transfer is determined by a 21-base-pair sequence present at the 3' end of VR. On the basis of patterns of marker transfer in response to variant selective pressures, we propose that a TR reverse transcript is mutagenized, integrated into VR as a single non-coding strand, and then partially converted to the parental VR sequence. This allows the diversity-generating system to minimize variability to the subset of bases under selection. Using the Bordetella phage cassette as a signature, we have identified numerous related elements in diverse bacteria. These elements constitute a new family of retroelements with the potential to confer selective advantages to their host genomes.
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