Selection for translational efficiency in genes associated with alphaproteobacterial gene transfer agents

Abstract

Gene transfer agents (GTAs) are virus-like elements that are encoded by some bacterial and archaeal genomes. The production of GTAs can be induced by the carbon depletion and results in host lysis and release of virus-like particles that contain mostly random fragments of the host DNA. The remaining members of a GTA-producing population act as GTA recipients by producing proteins needed for the GTA-mediated DNA acquisition. Here, we detect a codon usage bias towards codons with more readily available tRNAs in the RcGTA-like GTA genes of alphaproteobacterial genomes. Such bias likely improves the translational efficacy during GTA gene expression. While the strength of codon usage bias fluctuates substantially among individual GTA genes and across taxonomic groups, it is especially pronounced in Sphingomonadales, whose members are known to inhabit nutrient-depleted environments. By screening genomes for gene families with similar trends in codon usage biases to those in GTA genes, we found a gene that likely encodes head completion protein in some GTAs were it appeared missing, and 13 genes previously not implicated in GTA lifecycle. The latter genes are involved in various molecular processes, including the homologous recombination and transport of scarce organic matter. Our findings provide insights into the role of selection for translational efficiency in evolution of GTA genes, and outline genes that are potentially involved in the previously hypothesized integration of GTA-delivered DNA into the host genome. ImportanceHorizontal gene transfer (HGT) is a fundamental process that drives evolution of microorganisms. HGT can result a rapid dissemination of beneficial genes within and among microbial communities, and can be achieved via multiple mechanisms. One peculiar HGT mechanism involves viruses "domesticated" by some bacteria and archaea (their hosts). These so-called gene transfer agents (GTAs) are encoded in hosts genomes, produced under starvation conditions, and cannot propagate themselves as viruses. We show that GTA genes are under selection to improve efficiency of their translation when the host activates GTA production. The selection is especially pronounced in bacteria that occupy nutrient-depleted environments. Intriguingly, several genes involved in DNA incorporation into a genome are under similar selection pressure, suggesting that they may facilitate integration of GTA-delivered DNA into the host genome. Our findings underscore the potential importance of GTAs as a mechanism of HGT under nutrient-limited conditions, which are widespread in microbial habitats.