title: Evolutionary Characterization of the Retinitis Pigmentosa GTPase Regulator Gene.
abstract: OBJECTIVE
  The evolutionary conservation of the retinitis pigmentosa GTPase regulator (RPGR) gene was examined across vertebrate and invertebrate lineages to elucidate its function.
  
  
  METHODS
  Orthologous RPGR sequences from vertebrates and invertebrates were selected. Multiple sequence alignments, phylogenetic analyses, synteny, and gene structure comparisons were carried out. Expression of the alternatively spliced constitutive (RPGR(const) or RPGR(ex1-19)) and RPGR(ORF15) isoforms was examined in developing and adult zebrafish.
  
  
  RESULTS
  Phylogenetic analyses and syntenic relationships were consistent with the selected sequences being true orthologues, although whole genome duplications in teleost fish resulted in a more complex picture. The splice form RPGR(const) was present in all vertebrate and invertebrate species but the defining carboxyl (C)-terminal exon of RPGR(ORF15) was absent from all invertebrates. The regulator of chromosome condensation (RCC1)-like domain adopts a seven-bladed β-propeller structure, which was present in both major splice forms and strongly conserved across evolution. The repetitive acidic region of RPGR(ORF15) showed a high rate of in-frame deletions/insertions across nine primate species, compared with flanking sequences, consistent with an unstable and rapidly evolving region. In zebrafish, RPGR(const) transcripts were most strongly expressed in early development, while the RPGR(ORF15) isoform showed highest expression in adult eye.
  
  
  CONCLUSIONS
  The regulator of chromosome condensation 1-like domain of RPGR was conserved in vertebrates and invertebrates, but RPGR(ORF15) was unique to vertebrates, consistent with a proposed role in the ciliary-based transport of cargoes such as rhodopsin, which is ∼10 times more abundant in vertebrate than invertebrate photoreceptors. The repetitive acidic region of RPGR(ORF15) shows a rapid rate of evolution, consistent with a mutation "hot spot."
authors.affiliation: Department of Life Sciences Glasgow Caledonian University, Glasgow, United Kingdom.
authors.forename: Rakesh Kotapati
authors.initials: RK
authors.lastname: Raghupathy
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gautier
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Dinesh C
authors.initials: DC
authors.lastname: Soares
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.affiliation: Department of Life Sciences Glasgow Caledonian University, Glasgow, United Kingdom.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Shu
mesh_terms: D000818:Animals; D016645:Aotidae; D002144:Callithrix; D002415:Cats; D006224:Cricetinae; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D005091:Exons; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D006071:Gorilla gorilla; D006922:Hylobates; D008252:Macaca fascicularis; D002679:Pan troglodytes; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D011817:Rabbits; D051381:Rats; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism; D012756:Sheep; D013552:Swine; D015027:Zebrafish
chemical_list: D005136:Eye Proteins; C099929:RPGR protein, human; D012313:RNA; D004247:DNA