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.

Living Organisms Author Their Read-Write Genomes in Evolution

“…DGRs are targeted DNA mutagenesis operators that are found in bacterial and bacteriophage genomes that promote rapid and repeated diversification of a specific region in a protein coding sequence [ 638 , 639 ]. DGR diversification utilizes a highly mutagenic reverse transcriptase to generate novel DNA segments for the incorporation into a specific region of the target coding sequence (“mutagenic homing”).…”

What viruses tell us about evolution and immunity: beyond Darwin?

“…118 The reverse transcriptase can also be part of diversity-generating retroelements (DGRs) that are found in bacterial and phage genomes. 119 DGRs utilize the infidelity of the reverse transcriptase to diversify DNA sequences. The prototype DGR of Bordetella bacteriophage BPP-1 is able to modify the phage's receptor specificity and thereby alter tropism.…”

First crAss-Like Phage Genome Encoding the Diversity-Generating Retroelement (DGR)

“…One of the remarkable systems responsible for the variability of prokaryotic microorganisms are the diversity generating retroelements (DGRs), which use reverse transcription to introduce huge numbers of nucleotide substitutions in specific target genes [8,9]. The DGR has been initially discovered in the genome of the temperate Bordetella phage BPP-1 [10], and found to provide changes in the host-recognizing structures of Bordetella phages, hence enabling phage adaptation to dynamic changes on the surface of the Bordetella host [10,11].…”

“…A crucial element of each DGR is the gene encoding reverse transcriptase (RT). This enzyme plays an important role in exchanging between two repeats, which have similar nucleotide sequences, during a process called mutagenic retrohoming [8,9,12]. One repeat is a template repeat (TR) while the other is a variable repeat (VR), the latter of which is often located at the 3 -end of the target gene.…”