Selection for reducing energy cost of protein production drives the GC content and amino acid composition bias in gene transfer agents

Abstract

Gene transfer agents (GTAs) are virus-like elements integrated into bacterial genomes, particularly, those of Alphaproteobacteria. The GTAs can be induced under nutritional stress, incorporate random fragments of bacterial DNA into mini-phage particles, lyse the host cells and infect neighboring bacteria, thus enhancing horizontal gene transfer. We show that the GTA genes evolve under pronounced positive selection for the reduction of the energy cost of protein production as shown by comparison of the amino acid compositions with both homologous viral genes and host genes. The energy saving in GTA genes is comparable to or even more pronounced than that in the genes encoding the most abundant, essential bacterial proteins. In cases when viruses acquire genes from GTAs, the bias in amino acid composition disappears in the course of evolution, showing that reduction of the energy cost of protein is an important factor of evolution of GTAs but not bacterial viruses. These findings strongly suggest that GTAs are bacterial adaptations rather than selfish, virus-like elements. Because GTA production kills the host cell and does not propagate the GTA genome, it appears likely that the GTAs are retained in the course of evolution via kin or group selection. Therefore, we hypothesize that GTA facilitate the survival of bacterial populations under energy-limiting conditions through the spread of metabolic and transport capabilities via horizontal gene transfer and increase of nutrient availability resulting from the altruistic suicide of GTA-producing cells. ImportanceKin and group selection remain controversial topics in evolutionary biology. We argue that these types of selection are likely to operate in bacterial populations by showing that bacterial Gene Transfer Agents (GTAs), but not related viruses, evolve under positive selection for the reduction of the energy cost of a GTA particle production. We hypothesize that GTAs are dedicated devices for the survival of bacteria under the conditions of nutrient limitation. The benefits conferred by GTAs under nutritional stress appear to include horizontal dissemination of genes that could provide bacteria with enhanced capabilities for nutrient utilization and the increase of nutrient availability through the lysis of GTA-producing bacteria.

Phylogenetic evidence of headful packaging strategy in gene transfer agents

“…With the newfound support for a single origin of RcGTA-like TerLs from a TerL of a headful-packaging phage, we propose that a headful-packaging TerL in the RcGTA ancestor underwent key changes that resulted in the switch from packaging the GTA genome to packaging random, small pieces of the host genome (Hynes et al, 2012) with a substantially lower density of DNA in the capsid (Bárdy et al, 2020). The selection for reduced energy cost of GTA protein production that apparently occurred after the origin of RcGTA-like elements in alphaproteobacteria (Kogay et al, 2020) makes it challenging to pinpoint amino acid changes in GTA TerLs that contribute to this transition.…”

“…In position 292, 99% of the group 3 TerLs, but only 4% of the group 1 TerLs, contain cysteine, whereas 59% of the group 1 TerLs contain threonine. However, given that the threonine to cysteine substitution results in a reduction of the number of carbons per side chain, selection for the reduction in the energetic cost of GTA production (Kogay et al, 2020) cannot be excluded as a driver for this substitution. In position 282, 90% of the group 3 TerLs but no group 1 TerLs contain proline, whereas 64% of the group 1 TerLs but only 6% of the group 3 TerLs contain alanine.…”

“…The genomic loci that encode GTAs resemble prophages, indicating that GTAs evolved from viral ancestors. Although the function of GTAs is not firmly established, the prevailing hypothesis is that GTAs are not defective prophages, but instead are agents of horizontal gene transfer that are maintained in prokaryotic genomes due to the advantages associated with gene exchange, particularly, in stressful conditions (Kogay et al, 2020;Lang et al, 2017).…”

A positive correlation between GC content and growth temperature in prokaryotes

“…It is a highly variable trait ranging from 8% to 75% (Basak et al 2010; Nguyen et al 2020; Mahajan and Agashe 2021). This genomic trait has been widely studied, and its evolution has been proposed to be associated with numerous mutational and selective forces driven by genetic, metabolic, and ecological factors (Foerstner et al 2005; Hildebrand et al 2010; Mann and Chen 2010; Raghavan et al 2012; Wu et al 2012; Agashe and Shankar 2014; Glemin et al 2014; Šmarda et al 2014; Reichenberger et al 2015; Aslam et al 2019; Dietel et al 2019; Weissman et al 2019; Kogay et al 2020). Among them, the high temperature might be the most long-debating one (Galtier and Lobry 1997; Forsdyke 2021; Meyer 2021).…”

“…It is a highly variable trait ranging from 8% to 75% (1)(2)(3). This genomic trait has been widely studied, and its evolution has been proposed to be associated with numerous mutational and selective forces driven by genetic, metabolic, and ecological factors (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The high temperature might be the most long-debating (20)(21)(22).…”