Recent advances in exploring the composition and evolution of the prokaryotic selenoproteome.

Selenoproteins, a unique class of proteins critical for cellular antioxidant defense, are characterized by the incorporation of selenocysteine (Sec) in their active sites. Sec is co-translationally inserted into proteins via a specialized mechanism that reprograms the UGA codon to encode Sec, involving a specific RNA structure designated the Sec insertion sequence (SECIS) element and several essential enzymes. Although numerous selenoproteins have been identified in prokaryotes (primarily bacteria), the detection of selenoprotein genes in these organisms remains challenging, largely due to difficulties in distinguishing the Sec-encoding UGA codon from standard termination signals. In recent years, computational approaches for predicting selenoprotein genes, along with comparative genomic analyses of Sec-encoding machinery and selenoproteomes, have emerged as a promising and rapidly evolving field, offering new insights into Sec utilization in bacteria and archaea. This review provides a comprehensive overview of the latest advancements in the study of selenoproteins in prokaryotes. We summarize the molecular mechanisms underlying Sec biosynthesis and incorporation, and the structural diversity of SECIS elements in bacteria and archaea. We then describe current computational strategies for the identification of prokaryotic selenoprotein genes and present an updated, extensive catalog of prokaryotic selenoproteins documented to date, emphasizing those with well-established functions. Finally, we discuss recent progress in understanding the evolutionary dynamics of the Sec-encoding system and selenoproteins across prokaryotes, with a focus on the archaea-to-eukaryote transition of Sec machinery and selenoproteins. Overall, this review offers a unified perspective on the identification, functions, and evolution of selenoproteins in prokaryotes.