Comparative genomics on FGF7, FGF10, FGF22 orthologs, and identification of fgf25.

FGF family members are key molecules for the integrome network in the fields of oncology and regenerative medicine. Based on the comparative genomics on the CCND1-ORAOV1-FGF19-FGF4 locus, we demonstrated that rodent Fgf15 is the ortholog of human FGF19 in 2003. FGF7 (KGF), FGF10, and FGF22 constitute a subfamily among FGF family members. Here, comparative genomics analyses and comparative proteomics analyses on FGF7, FGF10, and FGF22 orthologs were performed. Chicken fgf22, zebrafish fgf22 and fgf25 genes, consisting of three exons, were identified within AC150066.1, BX927243.9 and CR854981.2 genome sequences, respectively. Zebrafish fgf22 (207 aa) showed 46.9%, 48.6% and 53.5% total amino-acid identity with human FGF7, FGF10 and FGF22, respectively. Zebrafish fgf25 (186 aa) showed 39.2%, 52.9% and 45.9% total amino-acid identity with human FGF7, FGF10 and FGF22, respectively. Phylogenetic analyses revealed that zebrafish fgf25 belongs to the FGF10 ortholog group. Zebrafish fgf25 was a novel FGF family member generated by the duplication of fgf10. FGF10-MRPS30-HCN1 locus at human chromosome 5p12 and FGF22-POLRMT-HCN2 locus at 19p13.3 were paralogous regions within the human genome. FGF7 mRNA was expressed in fetal heart, placenta, lung, kidney, and blood vessels. FGF10 mRNA was expressed in fetal lung, placenta, and uterus. FGF22 mRNA was expressed in hippocampus and ovarian fibrotheoma. FGF7 promoter with bHLH biding site and CCAAT box and FGF10 promoter with double bHLH biding sites were conserved well, while FGF22 promoter was significantly divergent. This is the first report on fgf25 gene and also on the comparative integromics analyses of FGF7, FGF10 and FGF22 orthologs.