The Metazoan Selenoproteome

Selenoproteins incorporate selenocysteine (Sec), a noncanonical amino acid analogous to cysteine with selenium in place of sulfur. Sec is inserted co-translationally via a unique recoding process that redefines the UGA stop codon in selenoprotein transcripts, marked by the Sec insertion sequence (SECIS) element in the 3′ untranslated region. Metazoans display striking diversity in their selenoproteomes. Although many animals, including mammals, depend on selenoproteins for critical roles in redox homeostasis and signaling, thyroid hormone metabolism, and stress responses, other lineages have lost the entire Sec pathway. We summarize the molecular biology of Sec, covering its biosynthesis, metabolism, insertion, and regulatory mechanisms. We then examine the evolutionary dynamics of selenoproteins across metazoa, including gene duplications, losses, and substitutions of Sec to cysteine. Finally, we present an updated survey of known metazoan selenoprotein families, detailing their structure, function, and phylogenetic distribution. Altogether, we offer a comprehensive view of selenoprotein evolution and function in animals.