title: Evolution of the vertebrate Pax4/6 class of genes with focus on its novel member, the Pax10 gene.
abstract: The members of the paired box (Pax) family regulate key developmental pathways in many metazoans as tissue-specific transcription factors. Vertebrate genomes typically possess nine Pax genes (Pax1-9), which are derived from four proto-Pax genes in the vertebrate ancestor that were later expanded through the so-called two-round (2R) whole-genome duplication. A recent study proposed that pax6a genes of a subset of teleost fishes (namely, acanthopterygians) are remnants of a paralog generated in the 2R genome duplication, to be renamed pax6.3, and reported one more group of vertebrate Pax genes (Pax6.2), most closely related to the Pax4/6 class. We propose to designate this new member Pax10 instead and reconstruct the evolutionary history of the Pax4/6/10 class with solid phylogenetic evidence. Our synteny analysis showed that Pax4, -6, and -10 originated in the 2R genome duplications early in vertebrate evolution. The phylogenetic analyses of relationships between teleost pax6a and other Pax4, -6, and -10 genes, however, do not support the proposed hypothesis of an ancient origin of the acanthopterygian pax6a genes in the 2R genome duplication. Instead, we confirmed the traditional scenario that the acanthopterygian pax6a is derived from the more recent teleost-specific genome duplication. Notably, Pax6 is present in all vertebrates surveyed to date, whereas Pax4 and -10 were lost multiple times in independent vertebrate lineages, likely because of their restricted expression patterns: Among Pax6-positive domains, Pax10 has retained expression in the adult retina alone, which we documented through in situ hybridization and quantitative reverse transcription polymerase chain reaction experiments on zebrafish, Xenopus, and anole lizard.
authors.affiliation: Department of Biology, University of Konstanz, GermanyInternational Max-Planck Research School (IMPRS) for Organismal Biology, University of Konstanz, GermanyPresent address: Department of Zoology, University of Oxford, United Kingdom.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Feiner
authors.affiliation: Department of Biology, University of Konstanz, GermanyInternational Max-Planck Research School (IMPRS) for Organismal Biology, University of Konstanz, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Department of Biology, University of Konstanz, GermanyInternational Max-Planck Research School (IMPRS) for Organismal Biology, University of Konstanz, GermanyPresent address: Genome Resource and Analysis Unit, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Hyogo, Japan shigehiro-kuraku@cdb.riken.jp.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Kuraku
mesh_terms: D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005136:Eye Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008116:Lizards / Q000145:classification / Q000235:genetics; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics; D014714:Vertebrates / Q000145:classification* / Q000235:genetics*; D014981:Xenopus / Q000145:classification / Q000235:genetics; D015027:Zebrafish / Q000145:classification / Q000235:genetics
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C491709:PAX4 protein, human; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins
keywords: Pax10; Pax4; Pax6; conserved synteny; gene duplication; gene loss