Composition and Evolution of the Vertebrate and Mammalian Selenoproteomes

Abstract

BackgroundSelenium 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 FindingsWe 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/SignificanceThis 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.

Selenoproteins and heat shock proteins play important roles in immunosuppression in the bursa of Fabricius of chickens with selenium deficiency

“…The selenoproteins belonging to the GPx family (GPx1-GPx6), Txnrd family (Txnrd1, Txnrd2, and Txnrd3), and the Dio family (Dio1, Dio2, and Dio3) play vital roles in redox regulation, antioxidant defense, the conversion of T4 to T3, and immune regulation in human diseases (Bellinger et al 2009;Pappas et al 2008). Other selenoproteins have also been identified in mammals and chickens, such as SPS2, Seli, Selk, Selm, Sel-15, Sepw1, Selh, Selv, Sepn1, Selo, Sepp1, Seli, Sels, and Selt (Mariotti et al 2012;Novoselov et al 2007). …”

“…In chicken, 25 selenoproteins have been identified (Mariotti et al 2012). Selenoproteins are recognized by their different characteristics and functions (Bellinger et al 2009;Pappas et al 2008).…”

Comparative selenoproteome analysis reveals a reduced utilization of selenium in parasitic platyhelminthes

“…Many of these newly predicted selenoproteins have been experimentally verified, implying that these computational approaches are highly efficient for selenoprotein identification. Recent comparative genomics analyses also revealed that many of these selenoproteins are widespread in many eukaryotes including both vertebrates and invertebrates (Jiang et al 2012;Mariotti et al 2012).…”

“…Thus, we considered them as the most indispensable selenoproteins in animals. Another selenoprotein family, SelR, is also included in this group because SelR is also reported to be present in many phyla of animals, especially all vertebrates (Mariotti et al 2012) . However, the fact that only Cys-containing homologs were found in, platyhelminthes, implying that it may have become selenium-independent in this phylum.…”

“…Several bioinformatics tools have been developed to identify the whole set of selenoproteins (or selenoproteome) that one organism may have (Kryukov et al 2003;Hatfield, Gladyshev,2002). These programs have successfully identified many new selenoproteins in bacteria, algae, insects, nematodes, and a variety of both invertebrates and vertebrates, implying that selenium plays an important role in all the three kingdoms of life (Castellano et al 2001;Kryukov & Gladyshev 2000;Lobanov et al 2006a;Lobanov et al 2006b;Mariotti et al 2013;Mariotti et al 2012;Novoselov et al 2002;Zhang et al 2005;Zhang & Gladyshev 2008;Zhang et al 2006). It is obvious that investigation of the selenoproteomes of various organisms is helpful for understanding evolutionary dynamics of selenium utilization as well as its relationship with different living conditions and lifestyles.…”