Comparative genomics and phylogenomic analyses of lysine riboswitch distributions in bacteria

Riboswitches are cis-regulatory elements that regulate the expression of genes involved in biosynthesis or transport of a ligand that binds to them. Among the nearly 40 classes of riboswitches discovered so far, three are known to regulate the concentration of biologically encoded amino acids glycine, lysine, and glutamine. While some comparative genomics studies of riboswitches focusing on their gross distribution across different bacterial taxa have been carried out recently, systematic functional annotation and analysis of lysine riboswitches and the genes they regulate are still lacking. We analyzed 2785 complete bacterial genome sequences to systematically identify 468 lysine riboswitches (not counting hits from multiple strains of the same species) and obtain a detailed phylogenomic map of gene-specific lysine riboswitch distribution across diverse prokaryotic phyla. We find that lysine riboswitches are most abundant in Firmicutes and Gammaproteobacteria where they are found upstream to both biosynthesis and/or transporter genes. They are relatively rare in all other prokaryotic phyla where if present they are primarily found upstream to operons containing many lysine biosynthesis genes. The genome-wide study of the genetic organisation of the lysine riboswitches show considerable variation both within and across different Firmicute orders. Correlating the location of a riboswitch with its genomic context and its phylogenetic relationship with other evolutionarily related riboswitch carrying species, enables identification and annotation of many lysine biosynthesis, transporter and catabolic genes. It also reveals previously unknown patterns of lysine riboswitch distribution and gene/operon regulation and allows us to draw inferences about the possible point of origin of lysine riboswitches. Additionally, evidence of horizontal transfer of riboswitches was found between Firmicutes and Actinobacteria. Our analysis provides a useful resource that will lead to a better understanding of the evolution of these regulatory elements and prove to be beneficial for exploiting riboswitches for developing targeted therapies.