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X. Xu, S.S. Zhang, C.J. Barnstable, J. Tombran–Tink; Phylogenetic Studies Of The Pedf Gene . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1762.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study was to use bioinformatic tools to detect, to assemble and compare PEDF genes in various species.
All sequence data were downloaded from NCBI databases and UCSC Genome Bioinformatics Site. BLAST, BLAT, ClustalW, and some python tools were used to detect, assemble and analyze the sequence data. The phylogenetic trees were constructed using "drawgram" from PHYLIP package.
The PEDF gene is located on human chromosome 17p13.3. In situ hybridization localized the PEDF gene to mouse chromosome 11. The fine structure of this region is preserved in other species including mouse, chick, xenopus and fish. We identified 19 novel serpins of which 9 represent PEDF genes. All PEDF genes showed the same 8 exon–7 intron structure with strong conservation of exon size but much greater variation in introns. The overall gene size varied from 43.8 kb in xenopus to 2.9 kb in fugu and tetraodon. The 5’ ag and 3’ gt intron/exon splice junctions were conserved in all the species. All PEDF genes encoded a secreted protein. This, plus specific features of the Reactive Center Loop, are characteristic of the PEDF subgroup of serpins. Only the proximal 200 bp shows extensive homology. The promoter region and introns of mammalian PEDF genes contain a large number of repetitive DNA elements. Phylogenetic clustering shows that PEDF is most closely related to serpin F2/a2–antiplasmin and to C1 inhibitor, both protease inhibitors. Homologous genes flanking PEDF were organized in the same order in xenopus, chick, and mammal but in fugu, tetraodon, and zebrafish they are organized into two or three subgroups dispersed onto separate chromosomes.
PEDF is highly conserved throughout the vertebrate kingdom. The arrangement of flanking genes suggests that the chromosome duplication in a common ancestor of fishes allowed dispersal of genes maintained in synteny in all other vertebrates examined. Because functional constraints tend to conserve essential biological sequences between distantly related organisms, the molecular phylogeny of PEDF provides new insights into its functional domains.
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