Comparative genomics on Fzd8 orthologs

Abstract

WNT signaling pathway networks with Hedgehog, Notch and FGF signaling pathways during carcinogenesis and embryogenesis. FZD8 is up-regulated in HeLa S3 and A549 cells. Here we identified and characterized rat Fzd8 gene by using bioinformatics. Rat Fzd8 gene was identified within AC131883.2 genome sequence. Rat Fzd8 (684 aa) showed 99.1, 96.8, 71.8 and 71.6% total amino-acid identity with mouse Fzd8, human FZD8, zebrafish fzd8 and Xenopus fzd8, respectively. Vertebrate Fzd8 orthologs were seven-transmembrane receptors with Frizzled (Fz) domain within the N-terminal extracellular region, leucine zipper motif around the fifth transmembrane domain, and Dishevelled (Dvl)-binding motif within the C-terminal cytoplasmic region. Two Asn-linked glycosylation sites within the N-terminal extracellular region were conserved among vertebrate Fzd8 orhologs. One Asn-linked glycosylation site within the second extracellular loop was conserved among mammalian Fzd8 orthologs, but not in Xenopus and zebrafish fzd8 orthologs. These facts indicate the molecular evolution of Fzd8 orthologs. The 5'-flanking region and exonic region were well conserved among mammalian Fzd8 orthologs. Nucleotide position 92950-94221 of AC131883.2 genome sequence was identified as the evolutionarily conserved promoter region of rat Fzd8 gene, and nucleotide position 133421-132134 of AL121749.14 genome sequence as the evolutionarily conserved promoter region of human FZD8 gene. Match program revealed that ELK1- and PAX4-binding sites were conserved between rat Fzd8 and human FZD8 promoters. This is the first report on the rat Fzd8 gene as well as on comparative genomics for Fzd8 orthologs.