Research
Reduced reliance on the trace element selenium during evolution of mammals
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* Corresponding author: Vadim N Gladyshev vgladyshev1@unl.edu
1 Department of Biochemistry, University of Nebraska, Lincoln, NE 68588, USA
2 Section on the Molecular Biology of Selenium, Laboratory of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Genome Biology 2008, 9:R62 doi:10.1186/gb-2008-9-3-r62
Published: 31 March 2008Abstract
Background
Selenium (Se) is an essential trace element that occurs in proteins in the form of selenocysteine (Sec). It is transported throughout the body in the form of Sec residues in Selenoprotein P (SelP), a plasma protein of unclear origin recently proposed as an experimental marker of dietary Se status.
Results
Here, we report that the amino-terminal domain of SelP is distantly related to ancestral bacterial thiol oxidoreductases of the thioredoxin superfamily, and that its carboxy-terminal Se transport domain may have originated in early metazoan evolution by de novo accumulation of Sec residues. Reconstruction of evolutionary changes in the Se transport domain indicates a decrease in Sec content of SelP specifically in the mammalian lineage via replacement of Sec with cysteine (Cys). Sec content of mammalian SelPs varies more than two-fold and is lowest in rodents and primates. Compared to mammals, fish show higher Sec content of SelP, larger selenoproteomes, elevated SelP gene expression, and higher levels of tissue Se. In addition, mammals replaced Sec with Cys in several proteins and lost several selenoproteins altogether, whereas such events are not found in fish.
Conclusion
These data suggest that evolution from fish to mammals was accompanied by decreased use of Sec and that analyses of SelP, selenoproteomes and Sec/Cys transitions provide a genetic marker of utilization of this trace element in vertebrates. The evolved reduced reliance on Se raises questions regarding the need to maximize selenoprotein expression by Se dietary supplements in situations when pathology is not imminent, a currently accepted practice.