title: Diversity-generating retroelements.
abstract: Parasite adaptation to dynamic host characteristics is a recurrent theme in biology. Diversity-generating retroelements (DGRs) are a newly discovered family of genetic elements that function to diversify DNA sequences and the proteins they encode. The prototype DGR was identified in a temperate bacteriophage, BPP-1, on the basis of its ability to generate variability in a gene that specifies tropism for receptor molecules on host Bordetella species. Tropism switching is a template-dependent, reverse transcriptase mediated process that introduces nucleotide substitutions at defined locations within a target gene. This cassette-based mechanism is theoretically capable of generating trillions of different amino acid sequences in a distal tail fiber protein, providing a vast repertoire of potential ligand-receptor interactions. Variable residues are displayed in the context of a specialized C-type lectin fold, which has evolved a unique solution for balancing protein diversity against structural stability. Homologous DGRs have been identified in the chromosomes of diverse bacterial species. These unique genetic elements have the potential to confer powerful selective advantages to their hosts, and their ability to generate novel binding specificities and dynamic antimicrobial agents suggests numerous applications.
authors: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors: Bob
authors: B
authors: Medhekar
authors: Jeff F
authors: JF
authors: Miller
mesh_terms: D001435:Bacteriophages / Q000235:genetics*; D001884:Bordetella / Q000821:virology*; D019143:Evolution, Molecular; D018626:Retroelements / Q000235:genetics*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D018626:Retroelements; D014764:Viral Proteins
references: Expert Rev Vaccines. 2007 Feb;6(1):47-56
references: 17280478
references: FEBS J. 2005 Dec;272(24):6179-217
references: 16336259
references: Genetics. 2005 Feb;169(2):1033-43
references: 15731520
references: Nat Immunol. 2006 Dec;7(12):1258-65
references: 17110942
references: Nat Rev Immunol. 2004 Feb;4(2):123-32
references: 15040585
references: Nat Struct Mol Biol. 2005 Oct;12(10):886-92
references: 16170324
references: Retrovirology. 2006;3:67
references: 17018135
references: Annu Rev Genet. 2004;38:1-35
references: 15568970
references: Structure. 2005 Aug;13(8):1173-82
references: 16084389
references: Nature. 2007 May 17;447(7142):338-41
references: 17429354
references: Microbiology. 2006 Jan;152(Pt 1):113-21
references: 16385121
references: Nucleic Acids Res. 2004;32(9):2880-8
references: 15155857
references: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17602-7
references: 17105809
references: J Biol Chem. 2006 Sep 1;281(35):25635-43
references: 16807240
references: J Bacteriol. 2006 Mar;188(5):1775-85
references: 16484188
references: Nature. 2004 Sep 23;431(7007):476-81
references: 15386016
references: Curr Opin Struct Biol. 2004 Oct;14(5):617-30
references: 15465324
references: Annu Rev Immunol. 2005;23:487-513
references: 15771579
references: Biochemistry. 2004 Apr 20;43(15):4490-500
references: 15078095
references: Infect Immun. 2004 Jul;72(7):3716-23
references: 15213111
references: Immunol Rev. 2006 Feb;209:253-73
references: 16448547
references: Nucleic Acids Res. 2006;34(19):e132
references: 17023486
references: PLoS Pathog. 2005 Dec;1(4):e45
references: 16389302
references: Nucleic Acids Res. 2006;34(19):5491-7
references: 17020921
references: Trends Immunol. 2006 Sep;27(9):421-7
references: 16860609
references: FEMS Microbiol Rev. 2004 Jun;28(3):291-318
references: 15449605
references: Science. 2002 Mar 15;295(5562):2091-4
references: 11896279
references: Clin Microbiol Rev. 2004 Jul;17(3):581-611, table of contents
references: 15258095
references: J Mol Biol. 2006 Apr 14;357(5):1383-93
references: 16490214
references: DNA Repair (Amst). 2006 Sep 8;5(9-10):1010-20
references: 16798113
references: Clin Microbiol Rev. 2005 Apr;18(2):326-82
references: 15831828
references: J Evol Biol. 2006 Nov;19(6):1931-8
references: 17040390
references: Cell Immunol. 2006 Feb;239(2):92-102
references: 16797504
references: J Bacteriol. 2004 Mar;186(5):1503-17
references: 14973019
references: Nat Rev Immunol. 2006 Oct;6(10):728-40
references: 16998507
references: PLoS Pathog. 2006 Feb;2(2):e10
references: 16485036
references: Bioessays. 2005 Aug;27(8):775-84
references: 16015595
references: Mol Microbiol. 2005 Apr;56(1):175-88
references: 15773988
references: Bioessays. 2006 Sep;28(9):913-22
references: 16937363