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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 SelI and its homologs.The multiple sequence alignment of the active site and preceding regions of CHPT1, CEPT1, and SelI is shown. Homologs are labeled with the annotated name. Proteins in the bottom section comprise a large group of diverse proteins containing the same domain. The most critical residues are marked in red. The residue in green marks the end of the first transmembrane domain. The cysteine residue near the active site emerged specifically in SelI proteins is marked in orange.The full length alignment is provided in Supplementary Figure S37 and the corresponding phylogenetic tree in Supplementary Figure S38.
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pone-0033066-g005: Multiple sequence alignment of SelI and its homologs.The multiple sequence alignment of the active site and preceding regions of CHPT1, CEPT1, and SelI is shown. Homologs are labeled with the annotated name. Proteins in the bottom section comprise a large group of diverse proteins containing the same domain. The most critical residues are marked in red. The residue in green marks the end of the first transmembrane domain. The cysteine residue near the active site emerged specifically in SelI proteins is marked in orange.The full length alignment is provided in Supplementary Figure S37 and the corresponding phylogenetic tree in Supplementary Figure S38.

Mentions: Selenoprotein I (SelI) is one of the least studied selenoproteins. It contains a highly conserved CDP-alcohol phosphatidyltransferase domain. This domain is typically encountered in choline phosphotransferases (CHPT1) and choline/ethanolamine phosphotransferases (CEPT1). CHPT1 catalyzes the transfer of choline to diacylglycerol from CDP-choline [52]. CEPT1 catalyzes an analogous reaction but accepts both choline and ethanolamine. SelI has seven predicted transmembrane domains, which correspond to the predicted topologies of CHPT1 and CEPT1. The most critical portion of this structure is located between the first and second transmembrane domains, and there are three aspartic acids, which are critical for function. Figure 5 shows an alignment of the active site region of SelI and its closest sequence homologs. The full alignment is shown in Supplementary Figure S37, and a phylogenetic tree based on that alignment is shown in Supplementary Figure S38. Not only are the three aspartic acids conserved in all SelI proteins, but the entire active region is highly similar between SelI and its homologs. The most prominent difference between SelI and its homologs is a C-terminal extension in SelI, which contains Sec. The function of this extension is unknown. We were unable to find Cys forms with homology to the SelI C-terminal extension.


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 SelI and its homologs.The multiple sequence alignment of the active site and preceding regions of CHPT1, CEPT1, and SelI is shown. Homologs are labeled with the annotated name. Proteins in the bottom section comprise a large group of diverse proteins containing the same domain. The most critical residues are marked in red. The residue in green marks the end of the first transmembrane domain. The cysteine residue near the active site emerged specifically in SelI proteins is marked in orange.The full length alignment is provided in Supplementary Figure S37 and the corresponding phylogenetic tree in Supplementary Figure S38.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0033066-g005: Multiple sequence alignment of SelI and its homologs.The multiple sequence alignment of the active site and preceding regions of CHPT1, CEPT1, and SelI is shown. Homologs are labeled with the annotated name. Proteins in the bottom section comprise a large group of diverse proteins containing the same domain. The most critical residues are marked in red. The residue in green marks the end of the first transmembrane domain. The cysteine residue near the active site emerged specifically in SelI proteins is marked in orange.The full length alignment is provided in Supplementary Figure S37 and the corresponding phylogenetic tree in Supplementary Figure S38.
Mentions: Selenoprotein I (SelI) is one of the least studied selenoproteins. It contains a highly conserved CDP-alcohol phosphatidyltransferase domain. This domain is typically encountered in choline phosphotransferases (CHPT1) and choline/ethanolamine phosphotransferases (CEPT1). CHPT1 catalyzes the transfer of choline to diacylglycerol from CDP-choline [52]. CEPT1 catalyzes an analogous reaction but accepts both choline and ethanolamine. SelI has seven predicted transmembrane domains, which correspond to the predicted topologies of CHPT1 and CEPT1. The most critical portion of this structure is located between the first and second transmembrane domains, and there are three aspartic acids, which are critical for function. Figure 5 shows an alignment of the active site region of SelI and its closest sequence homologs. The full alignment is shown in Supplementary Figure S37, and a phylogenetic tree based on that alignment is shown in Supplementary Figure S38. Not only are the three aspartic acids conserved in all SelI proteins, but the entire active region is highly similar between SelI and its homologs. The most prominent difference between SelI and its homologs is a C-terminal extension in SelI, which contains Sec. The function of this extension is unknown. We were unable to find Cys forms with homology to the SelI C-terminal extension.

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