Gene transfer agents: The ambiguous role of selfless viruses in genetic exchange and bacterial evolution

Gene transfer agents (GTAs) are genetic elements derived from ancestral bacteriophages that have become domesticated by the host. GTAs are present in diverse prokaryotic organisms, where they can facilitate horizontal gene transfer under certain conditions. Unlike typical bacteriophages, GTAs do not exhibit any preference for the replication or transfer of the genes encoding them; instead, they exhibit a remarkable capacity to package chromosomal, and sometimes extrachromosomal, DNA into virus-like capsids and disseminate it to neighboring cells. Because GTAs resemble defective prophages, identification of novel GTAs is not trivial. The detection of candidates relies on the genetic similarity to known GTAs, which has been fruitful in alpha-proteobacterial lineages but challenging in more distant bacteria. Here we consider several fundamental questions: What is the true prevalence of GTAs in prokaryote genomes? Given there are high costs for GTA production, what advantage do GTAs provide to the bacterial host to justify their maintenance? How is the bacterial chromosome recognized and processed for inclusion in GTA particles? This article highlights the challenges in comprehensively understanding GTAs' prevalence, function and DNA packaging method. Going forward, broad study of atypical GTAs and use of ecologically relevant conditions are required to uncover their true impact on bacterial chromosome evolution. Gene transfer agents (GTAs) have been maintained for millions of years as domesticated viruses in the genomes of various prokaryotes. GTAs produced by different species package the entire host chromosome but with species-specific biases in DNA content. GTAs do not preferentially propagate the genes encoding them and are inherently difficult to identify by bioinformatics, thus their prevalence is unknown. GTAs have been shown to mediate horizontal gene transfer and DNA repair, but the definitive evolutionary benefit of GTA production to the host has not been defined.image