Comparative genomics on Wnt11 gene

Non-canonical WNTs activate the planar cell polarity (PCP) pathway to induce cell motility and metastasis, while canonical WNTs activate the β-catenin-TCF pathway to induce carcinogenesis. WNT11 gene at human chromosome 11q13.5 encodes non-canonical WNT11 protein, which is applicable for regenerative medicine of heart diseases. Here, we identified and characterized rat Wnt11 gene by using bioinformatics. Rat Wnt11 gene, consisting of five exons, was identified within AC120107.3 genome sequence. Rat Wnt11 (354 aa) was a secreted protein with 24 conserved Cys residues and five Asn-linked glycosylation sites. Rat Wnt11 showed 99.4%, 97.5%, 84.5% and 76.0% total-amino-acid identity with mouse Wnt11, human WNT11, chicken wnt11 and zebrafish wnt11, respectively. Comparative proteomics revealed that the number of Asn-linked glycosylation sites increased during molecular evolution of Wnt11 orthologs. Comparative genomics revealed that exon 1, but not 5'-flanking region, was well conserved between rat Wnt11 and human WNT11 genes. Although conserved transcription-factor-binding site was not identified within 5'-flanking region of rat Wnt11 and human WNT11 genes, Nkx2-5-binding site within exon 1 was evolutionarily conserved among mammalian Wnt11 orthologs. Because Nkx2-5 and Wnt11 are key regulators of heart development, Wnt11 was predicted as a target gene of Nkx2-5 transcription factor during cardiac myocyte differentiation. This is the first report on rat Wnt11 gene as well as on comparative genomics for Wnt11 orthologs.