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Diversity-generating Retroelements in Phage and Bacterial Genomes
#MMPMID26104433
Guo H
; Arambula D
; Ghosh P
; Miller JF
Microbiol Spectr
2014[Dec]; 2
(6
): ? PMID26104433
show ga
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.
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