Selenium (Se) is an important micro nutrient that mainly occurs in protein sin the form of selenocy steine and in tRNAs in the form of selenouridine. In the past 20 years, several genes involved in Se utilization have been characterized in both prokaryotes and eukaryotes. However, Se homeostasis and the associated regulatory network are not fully understood. In this study, we conducted comparative genomics and phylogenetic analyses to examine the occurrence of all known Se utilization traits in prokaryotes.Our results revealed a highly mosaic pattern of species that useSe (indifferent forms) in spite that most organisms do not use this element. Further investigation of genomic context of known Se-related genes in different organisms suggested novel candidate genes that may participate in Se metabolism in bacteria and/or archaea. Among them, a membrane protein, YedE, which contains ten trans membrane domains and shows distant similarity to a sulfur transporter, is exclusively foundin Se-utilizing organisms, suggesting that it may be involved in Setransport. ALysR-like tran scription factor subfamily might be important for the regulation of Secbiosyn thesis and/or other Se-related genes. In addition, a small protein family DUF3343 is wide spread inSe-utilizing organisms, which probably serves as an important chaperone for Se trafficking within the cells. Finally, we proposed a simple model of Se homeostasis based on our findings. Our study reveals new candidate genes involved in Se metabolism in prokaryotes and should be useful for a further understanding of the complex metabolism and the roles of Se in biology
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