Pathogenic Variants in Selenoproteins and Selenocysteine Biosynthesis Machinery

Selenium is incorporated into selenoproteins as the 21st amino acid selenocysteine (Sec). There are 25 selenoproteins encoded in the human genome, and their synthesis requires a dedicated machinery. Most selenoproteins are oxidoreductases with important functions in human health. A number of disorders have been associated with deficiency of selenoproteins, caused by mutations in selenoprotein genes or Sec machinery genes. We discuss mutations that are known to cause disease in humans and report their allele frequencies in the general population. The occurrence of protein-truncating variants in the same genes is also presented. We provide an overview of pathogenic variants in selenoproteins genes from a population genomics perspective.

Patients with Osteoarthritis and Kashin-Beck Disease Display Distinct CpG Methylation Profiles in the DIO2, GPX3, and TXRND1 Promoter Regions

Objective We aimed to analyze deoxycytidine-deoxyguanosine dinucleotide (CpGs) methylation profiles in DIO2, GPX3, and TXNRD1 promoter regions in osteoarthritis (OA) and Kashin-Beck disease (KBD) patients. Methods Blood samples were collected from 16 primary OA patients and corresponding 16 healthy individuals and analyzed for methylations in the CpGs of DIO2, GPX3, and TXNRD1 promoter regions using MALDI-TOF-MS. The methylation profiles of these regions were then compared between OA and KBD patients. Results DIO2-1_CpG_2 and DIO2-1_CpG_3 methylations were significantly lower in OA than KBD patients ( P < 0.05). A similar trend was observed for GPX3-1_CpG_4, GPX3-1_CpG_7, GPX3-1_CpG_8.9.10, GPX3-1_CpG_13.14.15 and GPX3-1_CpG_16 ( P < 0.05) as well as TXNRD1-1_CpG_1 and TXNRD1-1_CpG_2 methylation between OA and KBD patients ( P < 0.05). However, there was no difference in methylation levels of other CpGs between the 2 groups ( P > 0.05). Conclusion OA and KBD patients display distinct methylation profiles in the CpG sites of DIO2, GPX3, and TXNRD1 promoter regions. These findings provide a strong background and new perspective for future studies on mechanisms underlying epigenetic regulation of selenoprotein genes associated with OA and KBD diseases.

The algal selenoproteomes

Background Selenium is an essential trace element, and selenocysteine (Sec, U) is its predominant form in vivo. Proteins that contain Sec are selenoproteins, whose special structural features include not only the TGA codon encoding Sec but also the SECIS element in mRNA and the conservation of the Sec-flanking region. These unique features have led to the development of a series of bioinformatics methods to predict and research selenoprotein genes. There have been some studies and reports on the evolution and distribution of selenoprotein genes in prokaryotes and multicellular eukaryotes, but the systematic analysis of single-cell eukaryotes, especially algae, has been very limited. Results In this study, we predicted selenoprotein genes in 137 species of algae by using a program we previously developed. More than 1000 selenoprotein genes were obtained. A database website was built to record these algae selenoprotein genes (www.selenoprotein.com). These genes belong to 42 selenoprotein families, including three novel selenoprotein gene families. Conclusions This study reveals the primordial state of the eukaryotic selenoproteome. It is an important clue to explore the significance of selenium for primordial eukaryotes and to determine the complete evolutionary spectrum of selenoproteins in all life forms.

The algal selenoproteomes

Background: Selenium is an essential trace element, and selenocysteine (Sec, U) is its predominant form in vivo. Proteins that contain Sec are selenoproteins, whose special structural features include not only the TGA codon encoding Sec but also the SECIS element in mRNA and the conservation of the Sec-flanking region. These unique features have led to the development of a series of bioinformatics methods to predict and research selenoprotein genes. There have been some studies and reports on the evolution and distribution of selenoprotein genes in prokaryotes and multicellular eukaryotes, but the systematic analysis of single-cell eukaryotes, especially algae, has been very limited. Results: In this study, we predicted selenoprotein genes in 137 species of algae by using a program we previously developed. More than 1000 selenoprotein genes were obtained. A database website was built to record these algae selenoprotein genes (www.selenoprotein.com). These genes belong to 42 selenoprotein families, including three novel selenoprotein gene families. Conclusions: This study reveals the primordial state of the eukaryotic selenoproteome . It is an important clue to explore the significance of selenium for primordial eukaryotes and to determine the complete evolutionary spectrum of selenoproteins in all life forms.

The algal selenoproteomes

Background:Selenium is an essential trace element, and selenocysteine (Sec, U) is its predominant form in vivo. Proteins that contain Sec are selenoproteins, whose special structural features include not only the TGA codon encoding Sec, but also the SECIS element in mRNA and the conservation of the Sec flanking region. These unique features have led to developing a series of bioinformatics methods to predict and research selenoprotein genes. There are some studies and reports on the evolution and distribution of selenoprotein genes in prokaryotes and multicellular eukaryotes, but the systematic analysis of single-cell eukaryotes, especially algae, is very limited.Results:In this study, we predicted selenoprotein genes in 137 species of algae by using a program we previously developed. More than 1000 selenoprotein genes were obtained. A database website was built to hold these algae selenoprotein genes (www.selenoprotein.com). These genes belong to 42 selenoprotein families, including three novel selenoprotein gene families.Conclusions:This study reveals the primordial state of the eukaryotic selenoproteome. It is an important clue to explore the significance of selenium for primordial eukaryotes and to build the whole evolutionary spectrum of selenoproteins for all life.

The algal selenoproteomes

Background: Selenium is an important trace element, and selenocysteine is its predominant form in vivo. The protein containing selenocysteine is selenoprotein, whose special structural features include not only the TGA codon encoding selenocysteine, but also the SECIS element in mRNA and the conservation of selenocysteine flanking region. These special features have led to the development of a series of bioinformatics methods for the prediction and research of selenoprotein genes. There are some studies and reports on the evolution and distribution of selenoprotein genes in prokaryotes and multicellular eukaryotes, but the systematic analysis of single-cell eukaryotes, especially algae, is very limited. Results: In this study, we predicted selenoprotein genes in 137 species of algae by using a program we previously developed. More than 1000 selenoprotein genes were obtained. A database website was built to hold these algae selenoprotein genes (www.selenoprotein.com). These genes belong to 42 selenoprotein families, including three novel selenoprotein gene families. Conclusions: This study reveals the primordial state of the eukaryotic selenoproteome. It is an important clue to explore the significance of selenium for primordial eukaryotes and to build the whole evolutionary spectrum of selenoproteins for all life.

The algal selenoproteomes

Background: Selenium is an important trace element, and selenoprotein is its predominant form in vivo. The special structural features of selenoprotein genes have led to the development of a series of bioinformatics methods for the prediction and research of selenoprotein genes. There are some studies and reports on the evolution and distribution of selenoprotein genes in prokaryotes and multicellular eukaryotes, but the systematic analysis of single-cell eukaryotes, especially algae, is very limited. Results: In this study, we predicted selenoprotein genes in 137 species of algae by using a program we previously developed. More than 1000 selenoprotein genes were obtained. A database website was built to hold these algae selenoprotein genes (www.selenoprotein.com). These genes belong to 42 selenoprotein families, including three novel selenoprotein gene families. Conclusions: This study reveals the primordial state of the eukaryotic selenoproteome. It is an important clue to explore the significance of selenium for primordial eukaryotes and to build the whole evolutionary spectrum of selenoproteins for all life.