title: Composition and evolution of the vertebrate and mammalian selenoproteomes.
abstract: BACKGROUND
  Selenium is an essential trace element in mammals due to its presence in proteins in the form of selenocysteine (Sec). Human genome codes for 25 Sec-containing protein genes, and mouse and rat genomes for 24.
  
  
  RESULTS
  We characterized the selenoproteomes of 44 sequenced vertebrates by applying gene prediction and phylogenetic reconstruction methods, supplemented with the analyses of gene structures, alternative splicing isoforms, untranslated regions, SECIS elements, and pseudogenes. In total, we detected 45 selenoprotein subfamilies. 28 of them were found in mammals, and 41 in bony fishes. We define the ancestral vertebrate (28 proteins) and mammalian (25 proteins) selenoproteomes, and describe how they evolved along lineages through gene duplication (20 events), gene loss (10 events) and replacement of Sec with cysteine (12 events). We show that an intronless selenophosphate synthetase 2 gene evolved in early mammals and replaced functionally the original multiexon gene in placental mammals, whereas both genes remain in marsupials. Mammalian thioredoxin reductase 1 and thioredoxin-glutathione reductase evolved from an ancestral glutaredoxin-domain containing enzyme, still present in fish. Selenoprotein V and GPx6 evolved specifically in placental mammals from duplications of SelW and GPx3, respectively, and GPx6 lost Sec several times independently. Bony fishes were characterized by duplications of several selenoprotein families (GPx1, GPx3, GPx4, Dio3, MsrB1, SelJ, SelO, SelT, SelU1, and SelW2). Finally, we report identification of new isoforms for several selenoproteins and describe unusually conserved selenoprotein pseudogenes.
  
  
  CONCLUSIONS
  This analysis represents the first comprehensive survey of the vertebrate and mammal selenoproteomes, and depicts their evolution along lineages. It also provides a wealth of information on these selenoproteins and their forms.
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Marco
authors.initials: M
authors.lastname: Mariotti
authors.forename: Perry G
authors.initials: PG
authors.lastname: Ridge
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Lobanov
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Pringle
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigo
authors.forename: Dolph L
authors.initials: DL
authors.lastname: Hatfield
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D008322:Mammals / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D020033:Protein Isoforms / Q000145:classification / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D011544:Pseudogenes / Q000235:genetics; D051140:Selenoproteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D020543:Proteome; D051140:Selenoproteins