title: Tropism switching in Bordetella bacteriophage defines a family of diversity-generating retroelements.
abstract: Bordetella bacteriophages generate diversity in a gene that specifies host tropism. 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). 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.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Doulatov
authors.forename: Asher
authors.initials: A
authors.lastname: Hodes
authors.forename: Lixin
authors.initials: L
authors.lastname: Dai
authors.forename: Neeraj
authors.initials: N
authors.lastname: Mandhana
authors.forename: Minghsun
authors.initials: M
authors.lastname: Liu
authors.forename: Rajendar
authors.initials: R
authors.lastname: Deora
authors.forename: Robert W
authors.initials: RW
authors.lastname: Simons
authors.forename: Steven
authors.initials: S
authors.lastname: Zimmerly
authors.forename: Jeff F
authors.initials: JF
authors.lastname: Miller
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D001435:Bacteriophages / Q000201:enzymology / Q000235:genetics* / Q000502:physiology*; D001483:Base Sequence; D005075:Biological Evolution; D001884:Bordetella / Q000145:classification / Q000821:virology*; D019295:Computational Biology; D005814:Genes, Viral / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D016679:Genome, Viral; D006790:Host-Parasite Interactions; D016296:Mutagenesis / Q000235:genetics*; D010802:Phylogeny; D011110:Polymorphism, Genetic / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D018626:Retroelements / Q000235:genetics / Q000502:physiology*; D012641:Selection, Genetic; D013045:Species Specificity; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D018626:Retroelements; D012194:RNA-Directed DNA Polymerase