title: Co-orthology of Pax4 and Pax6 to the fly eyeless gene: molecular phylogenetic, comparative genomic, and embryological analyses.
abstract: The functional equivalence of Pax6/eyeless genes across distantly related animal phyla has been one of central findings on which evo-devo studies is based. In this study, we show that Pax4, in addition to Pax6, is a vertebrate ortholog of the fly eyeless gene (and its duplicate, twin of eyeless [toy] gene, unique to Insecta). Molecular phylogenetic trees published to date placed the Pax4 gene outside the Pax6/eyeless subgroup as if the Pax4 gene originated from a gene duplication before the origin of bilaterians. However, Pax4 genes had only been reported for mammals. Our molecular phylogenetic analysis, including previously unidentified teleost fish pax4 genes, equally supported two scenarios: one with the Pax4-Pax6 duplication early in vertebrate evolution and the other with this duplication before the bilaterian radiation. We then investigated gene compositions in the genomic regions containing Pax4 and Pax6, and identified (1) conserved synteny between these two regions, suggesting that the Pax4-Pax6 split was caused by a large-scale duplication and (2) its timing within early vertebrate evolution based on the duplication timing of the members of neighboring gene families. Our results are consistent with the so-called two-round genome duplications in early vertebrates. Overall, the Pax6/eyeless ortholog is merely part of a 2:2 orthology relationship between vertebrates (with Pax4 and Pax6) and the fly (with eyeless and toy). In this context, evolution of transcriptional regulation associated with the Pax4-Pax6 split is also discussed in light of the zebrafish pax4 expression pattern that is analyzed here for the first time.
authors.affiliation: Laboratory for Zoology and Evolutionary Biology, Department of Biology, University of Konstanz, Universitätsstrasse 10, 78464, Konstanz, Germany.
authors.forename: Tereza
authors.initials: T
authors.lastname: Manousaki
authors.forename: Nathalie
authors.initials: N
authors.lastname: Feiner
authors.forename: Gerrit
authors.initials: G
authors.lastname: Begemann
authors.forename: Axel
authors.initials: A
authors.lastname: Meyer
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Kuraku
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D005136:Eye Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D020440:Gene Duplication; D018507:Gene Expression Regulation, Developmental; D049750:Genome, Insect / Q000235:genetics; D018398:Homeodomain Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D012097:Repressor Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D029961:Zebrafish Proteins; C113278:ey protein, Drosophila