1. Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA
2. The Molecular Biology Institute, University of California, Los Angeles, California 90095, USA
3. Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada
4. These authors contributed equally to this work

Correspondence to: Jeff F. Miller^1,2 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.

1. Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA
2. The Molecular Biology Institute, University of California, Los Angeles, California 90095, USA
3. Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada
4. These authors contributed equally to this work

Correspondence to: Jeff F. Miller^1,2 Email: jfmiller@ucla.edu

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