PT - JOURNAL ARTICLE AU - Marco Mariotti AU - Didac Santesmasses AU - Salvador Capella-Gutierrez AU - Andrea Mateo AU - Carme Arnan AU - Rory Johnson AU - Salvatore D’Aniello AU - Sun Hee Yim AU - Vadim N Gladyshev AU - Florenci Serras AU - Montserrat Corominas AU - Toni Gabaldón AU - Roderic Guigé TI - Evolution of selenophosphate synthetases: emergence and relocation of function through independent duplications and recurrent subfunctionalization AID - 10.1101/014928 DP - 2015 Jan 01 TA - bioRxiv PG - 014928 4099 - http://biorxiv.org/content/early/2015/02/05/014928.short 4100 - http://biorxiv.org/content/early/2015/02/05/014928.full AB - SPS catalyzes the synthesis of selenophosphate, the selenium donor for the synthesis of the amino acid selenocysteine (Sec), incorporated in selenoproteins in response to the UGA codon. SPS is unique among proteins of the selenoprotein biosynthesis machinery in that it is, in many species, a selenoprotein itself, although, as in all selenoproteins, Sec is often replaced by cysteine (Cys). In metazoan genomes we found, however, SPS genes with lineage specific substitutions other than Sec or Cys. Our results show that these non-Sec, non-Cys SPS genes originated through a number of independent gene duplications of diverse molecular origin from an ancestral selenoprotein SPS gene. Although of independent origin, complementation assays in fly mutants show that these genes share a common function, which most likely emerged in the ancestral metazoan gene. This function appears to be unrelated to selenophosphate synthesis, since all genomes encoding selenoproteins contain Sec or Cys SPS genes (SPS2), but those containing only non-Sec, non-Cys SPS genes (SPS1) do not encode selenoproteins. Thus, in SPS genes, through parallel duplications and subsequent convergent subfunctionalization, two functions initially carried by a single gene are recurrently segregated at two different loci. RNA structures enhancing the readthrough of the Sec-UGA codon in SPS genes, which may be traced back to prokaryotes, played a key role in this process. The SPS evolutionary history in metazoans constitute a remarkable example of the emergence and evolution of gene function. We have been able to trace this history with unusual detail thanks to the singular feature of SPS genes, wherein the amino acid at a single site determines protein function, and, ultimately, the evolutionary fate of an entire class of genes.SecselenocysteineSeseleniumSeUselenouridineSePselenophosphateSPSselenophosphate synthetaseSelDselenophosphate synthetase (prokaryotes)SelAselenocysteine synthase (prokaryotes)ybbBselenouridine synthase (prokaryotes)CyscysteineArgarginineThrthreonineGlyglycineLeuleucine