While the genome sequence and gene content are available for an increasing 
number of organisms, eukaryotic selenoproteins remain poorly characterized. The 
dual role of the UGA codon confounds the identification of novel selenoprotein 
genes. Here, we describe a comparative genomics approach that relies on the 
genome-wide prediction of genes with in-frame TGA codons, and the subsequent 
comparison of predictions from different genomes, wherein conservation in 
regions flanking the TGA codon suggests selenocysteine coding function. 
Application of this method to human and fugu genomes identified a novel 
selenoprotein family, named SelU, in the puffer fish. The 
selenocysteine-containing form also occurred in other fish, chicken, sea urchin, 
green algae and diatoms. In contrast, mammals, worms and land plants contained 
cysteine homologues. We demonstrated selenium incorporation into chicken SelU 
and characterized the SelU expression pattern in zebrafish embryos. Our data 
indicate a scattered evolutionary distribution of selenoproteins in eukaryotes, 
and suggest that, contrary to the picture emerging from data available so far, 
other taxa-specific selenoproteins probably exist.