Abstract
By competing for the acquisition of essential nutrients, Helicobacter pylori has the unique ability to persist in the human stomach, also causing nutritional insufficiencies in the host. Although the H. pylori genome apparently encodes selenocysteine synthase (SelA, HP1513), a key pyridoxal phosphate (PLP)-dependent enzyme for the incorporation of selenium into bacterial proteins, nothing is known about the use of this essential element in protein synthesis by this pathogen. We analyzed the evolution of the complete machinery for incorporation of selenium into proteins and the selenoproteome of several H. pylori strains and related Epsilonproteobacteria. Our searches identified the presence of selenoproteins-including the previously unknown DUF466 family-in various Epsilonproteobacteria, but not in H. pylori. We found that a complete system for selenocysteine incorporation was present in the Helicobacteriaceae ancestor and has been recently lost before the split of Helicobacter acinonychis and H. pylori. Our results indicate that H. pylori, at variance with other gastric and enterohepatic Helicobacter, does not use selenocysteine in protein synthesis and does not use selenium for tRNA wobble base modification. However, selA has survived as a functional gene, having lost the domain for the binding of selenocysteine tRNA, but maintaining the ability to bind the PLP cofactor. The evolutionary modifications described for the SelA protein of H. pylori find parallels in other bacterial and archaeal species, suggesting that an alternative enzymatic function is hidden in many proteins annotated as selenocysteinyl-tRNA synthase.