title: Diversity-generating Retroelements in Phage and Bacterial Genomes.
abstract: Diversity-generating retroelements (DGRs) are DNA diversification machines found in diverse bacterial and bacteriophage genomes that accelerate the evolution of ligand-receptor interactions. Diversification results from a unidirectional transfer of sequence information from an invariant template repeat (TR) to a variable repeat (VR) located in a protein-encoding gene. Information transfer is coupled to site-specific mutagenesis in a process called mutagenic homing, which occurs through an RNA intermediate and is catalyzed by a unique, DGR-encoded reverse transcriptase that converts adenine residues in the TR into random nucleotides in the VR. In the prototype DGR found in the Bordetella bacteriophage BPP-1, the variable protein Mtd is responsible for phage receptor recognition. VR diversification enables progeny phage to switch tropism, accelerating their adaptation to changes in sequence or availability of host cell-surface molecules for infection. Since their discovery, hundreds of DGRs have been identified, and their functions are just beginning to be understood. VR-encoded residues of many DGR-diversified proteins are displayed in the context of a C-type lectin fold, although other scaffolds, including the immunoglobulin fold, may also be used. DGR homing is postulated to occur through a specialized target DNA-primed reverse transcription mechanism that allows repeated rounds of diversification and selection, and the ability to engineer DGRs to target heterologous genes suggests applications for bioengineering. This chapter provides a comprehensive review of our current understanding of this newly discovered family of beneficial retroelements.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine Columbia, MO 65212.
authors.forename: Huatao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095.
authors.forename: Diego
authors.initials: D
authors.lastname: Arambula
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093.
authors.forename: Partho
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095.
authors.forename: Jeff F
authors.initials: JF
authors.lastname: Miller
mesh_terms: D000220:Adaptation, Biological; D001419:Bacteria / Q000235:genetics*; D001435:Bacteriophages / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D014644:Genetic Variation; D016296:Mutagenesis; D018626:Retroelements
chemical_list: D004269:DNA, Bacterial; D004279:DNA, Viral; D018626:Retroelements