Selenocysteine genes found and active in many mycobacteria

The Mycobacterium genus contains more than 190 species that live in many different environments; some are harmless, while others cause serious diseases in people and animals such as tuberculosis (TB) and leprosy. SelenoCysteine (SeC) is an unusual amino acid found across all domains of life, and it is incorporated into proteins by a specific set of genes and molecular tools. In this study led by corresponding author Leif A. Kirsebom, researchers examined 244 mycobacterial genomes to see which species carry the genetic machinery needed to make and use SeC. They looked specifically for genes called selA, selB, selC and selD that together build the SeC pathway, and for selenoprotein genes such as fdhA that actually use SeC in proteins. The team reports that roughly 40% of the genomes surveyed contain both the SeC-machinery genes and at least one selenoprotein gene, indicating that a substantial fraction of mycobacteria have the capacity to synthesize and use SelenoCysteine.

To explore whether these genes are not only present but also active, the researchers used RNA-Seq to measure transcript levels of the SeC-machinery genes and fdhA. The analysis covered different mycobacterial species and conditions, and showed that these genes are transcribed — meaning they produce RNA — in those species that retain the machinery. The presence of selA, selB, selC and selD and fdhA was found in roughly 40% of the 244 genomes surveyed, and this presence was distributed evenly between slow and rapid growing mycobacteria. The study also found evidence that these genes were acquired through horizontal gene transfer rather than inherited uniformly, and that some lineages subsequently lost the genes over the course of evolution. An intriguing genomic detail is that selC (the tRNASeC gene) sits immediately upstream of selA-selB, and the authors suggest this arrangement may help regulate the expression of selA-selB based on their RNA-Seq observations.

These findings expand our basic understanding of how selenocysteine metabolism is organized and how it has changed within the Mycobacterium genus. Showing that SeC machinery and the selenoprotein fdhA are both present and transcribed in many species means researchers must consider SeC biology when comparing metabolic capabilities across mycobacteria, including those that cause disease and those that do not. The evidence for horizontal gene transfer and for repeated loss of these genes highlights a dynamic evolutionary picture: some species picked up the SeC toolkit and kept it, while others discarded it. The suggested regulatory role of selC placed directly upstream of selA-selB raises new questions about how tRNA genes and protein synthesis factors are co-regulated. Altogether, the work reported by Leif A. Kirsebom and colleagues provides a clearer map of where SeC pathways exist in this diverse genus and points to new directions for studying mycobacterial metabolism and evolution.