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Composition and evolution of the vertebrate and mammalian selenoproteomes.

Mariotti M, Ridge PG, Zhang Y, Lobanov AV, Pringle TH, Guigo R, Hatfield DL, Gladyshev VN - PLoS ONE (2012)

Bottom Line: In total, we detected 45 selenoprotein subfamilies. 28 of them were found in mammals, and 41 in bony fishes.Mammalian thioredoxin reductase 1 and thioredoxin-glutathione reductase evolved from an ancestral glutaredoxin-domain containing enzyme, still present in fish.It also provides a wealth of information on these selenoproteins and their forms.

View Article: PubMed Central - PubMed

Affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.

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.

Methodology/principal findings: 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/significance: 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.

Show MeSH
Multiple sequence alignment of selenoprotein genes and pseudogenes.A. GPx1. Multiple sequence alignment of human and chimpanzee GPx1 pseudogenes. B. SelW. The last residue of each exon is marked in black and Sec in red. Residues marked in green are described in the text. C. SECIS elements of SelW and SelW pseudogene.
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pone-0033066-g007: Multiple sequence alignment of selenoprotein genes and pseudogenes.A. GPx1. Multiple sequence alignment of human and chimpanzee GPx1 pseudogenes. B. SelW. The last residue of each exon is marked in black and Sec in red. Residues marked in green are described in the text. C. SECIS elements of SelW and SelW pseudogene.

Mentions: Among the 11 selenoproteins with pseudogenes, SelK had more than any other selenoprotein (27 pseudogenes in 11 organisms), and rodents had the highest number. For example, mouse and rat had 5 and 4 SelK pseudogenes, respectively. SelW was another selenoprotein, which had many pseudogenes (19 in 13 organisms). An interesting GPx1 pseudogene was identified in humans and chimpanzees. The active site (surrounding the Sec) was conserved in both the functional and pseudogene versions of GPx1 and the overall conservation was quite high (Figure 7A). Three codon positions were particularly interesting (positions 6, 114, and 123). At each of these positions the residues translated from the pseudogenes matched, but were different than the residues in the corresponding position in GPx1. Therefore, it appeared the GPx1 pseudogene had been maintained since the human/chimpanzee split with few differences between the human and chimpanzee copies of the pseudogene. Furthermore, SECIS elements were also intact in these pseudogenes. However, a single base mutation at amino acid 161 in the human pseudogene sequence (TGG->TAG) resulted in a premature stop codon downstream of the active site. Due to this mutation and no supporting EST data, it is unlikely that this pseudogene is expressed. The Ka/Ks ratio (used as an indicator of the selective pressure) was 1.58 for this gene, which suggested the possibility of positive selection.


Composition and evolution of the vertebrate and mammalian selenoproteomes.

Mariotti M, Ridge PG, Zhang Y, Lobanov AV, Pringle TH, Guigo R, Hatfield DL, Gladyshev VN - PLoS ONE (2012)

Multiple sequence alignment of selenoprotein genes and pseudogenes.A. GPx1. Multiple sequence alignment of human and chimpanzee GPx1 pseudogenes. B. SelW. The last residue of each exon is marked in black and Sec in red. Residues marked in green are described in the text. C. SECIS elements of SelW and SelW pseudogene.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3316567&req=5

pone-0033066-g007: Multiple sequence alignment of selenoprotein genes and pseudogenes.A. GPx1. Multiple sequence alignment of human and chimpanzee GPx1 pseudogenes. B. SelW. The last residue of each exon is marked in black and Sec in red. Residues marked in green are described in the text. C. SECIS elements of SelW and SelW pseudogene.
Mentions: Among the 11 selenoproteins with pseudogenes, SelK had more than any other selenoprotein (27 pseudogenes in 11 organisms), and rodents had the highest number. For example, mouse and rat had 5 and 4 SelK pseudogenes, respectively. SelW was another selenoprotein, which had many pseudogenes (19 in 13 organisms). An interesting GPx1 pseudogene was identified in humans and chimpanzees. The active site (surrounding the Sec) was conserved in both the functional and pseudogene versions of GPx1 and the overall conservation was quite high (Figure 7A). Three codon positions were particularly interesting (positions 6, 114, and 123). At each of these positions the residues translated from the pseudogenes matched, but were different than the residues in the corresponding position in GPx1. Therefore, it appeared the GPx1 pseudogene had been maintained since the human/chimpanzee split with few differences between the human and chimpanzee copies of the pseudogene. Furthermore, SECIS elements were also intact in these pseudogenes. However, a single base mutation at amino acid 161 in the human pseudogene sequence (TGG->TAG) resulted in a premature stop codon downstream of the active site. Due to this mutation and no supporting EST data, it is unlikely that this pseudogene is expressed. The Ka/Ks ratio (used as an indicator of the selective pressure) was 1.58 for this gene, which suggested the possibility of positive selection.

Bottom Line: In total, we detected 45 selenoprotein subfamilies. 28 of them were found in mammals, and 41 in bony fishes.Mammalian thioredoxin reductase 1 and thioredoxin-glutathione reductase evolved from an ancestral glutaredoxin-domain containing enzyme, still present in fish.It also provides a wealth of information on these selenoproteins and their forms.

View Article: PubMed Central - PubMed

Affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.

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.

Methodology/principal findings: 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/significance: 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.

Show MeSH