Conséquences immédiates et évolutives de transferts horizontaux entre génomes ayant des préférences d'usage de codons différentes

Codon usage preferences differ greatly between bacterial species. Here, we show that the codon composition of synonymous variants of the gentamicin resistance gene aacC1 impacts bacterial evolution and horizontal gene transfer outcomes.We first show synonymous variants of aacC1 confer a large range of resistance to gentamicin in all of the three species (A. baylyi, E. coli and P. aeruginosa) in which we transformed the gene. We determined that different variants rank better or worse depending on the host species, unveiling a species-variant interaction. Importantly, we found no significant relation between the similarity in codon preferences between the donor gene and receiving genome and the resistance levels we observe. We examined codon preferences on a local level, including intragenic sequence motifs but again found no overarching commonality between species, suggesting that codon choice affects phenotype on multiple levels in a species-specific manner. We did, however, determine that part of this species effect on resistance levels is due to differences in copy number of the plasmid carrying the resistance gene.To further understand if these immediate effects persist over time, we evolved a subset of aacC1 variants on a plasmid in the presence or absence of gentamicin for 365 generations. We show that in the presence of gentamicin, our synonymous variants converge in resistance phenotype. Inversely, in the absence of gentamicin, our synonymous variants maintain or lose resistance depending on variant, with the same variant differentially losing or maintaining resistance depending on the host species. We show that plasmid copy number evolves differently depending on the evolution condition and we determine a number of localised mutations in the OriV of pBBR1 linked to PCN evolution. We then identify a number of genes under selection in the presence of gentamicin, suggesting a positive epistatic relationship between the original resistance conferring gene aacC1 and a number of resistance-linked genes (GltA, CpxA, MexZ). Overall, our results show that differences in synonymous variation drive HGT and bacterial evolution outcomes, in a species-specific manner, dependent on environmental conditions.