Evolution of two metabolic genes involved in nucleotide and amino acid metabolism in Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is an opportunistic human pathogen causing various severe infections. Understanding genetic mechanisms of its metabolic versatility aids in developing novel antibacterial drugs and therapeutic strategies to address multidrug-resistant P. aeruginosa infections. The metabolism of nucleotides and amino acids contributes to the cycle of two key biological macromolecules in the genetic central dogma. Guanine deaminase (GuaD) catalyzes the deamination of guanine to produce xanthine to maintain the homeostasis of the nucleotide pool, and transporters specific to BCAAs (termed as BraT) import BCAAs to keep its intracellular availability level. However, little is known about the evolution of GuaD and BraT in P. aeruginosa population. Here, two copies turned out to be widespread in P. aeruginosa population for each of GuaD and BraT. The phylogenic analysis demonstrated that GuaD1 and BraB were inherited from the ancestor of Pseudomonas, while GuaD2 and BraZ were additionally acquired via evolutionary events in the ancestors of P. aeruginosa. The functional divergence of two copies was supported by different distribution patterns of dN/dS ratios, divergent expression levels, differentially co-expressed genes, and their functional enrichment modules with few intersections. Besides, some co-expressed genes with known functions are involved in infecting hosts, forming biofilm and resisting antibiotic treatment. Taken together, functional divergence following copy number increase and differentiation of co-expression networks might confer greater metabolic potential to P. aeruginosa, especially in response to host immune responses and antibiotic treatments in clinical settings.