Contributed equally to this work.
Co-orthology of Pax4 and Pax6 to the fly eyeless gene: molecular phylogenetic, comparative genomic, and embryological analyses
Article first published online: 20 SEP 2011
© 2011 Wiley Periodicals, Inc.
Evolution & Development
Volume 13, Issue 5, pages 448–459, September/October 2011
How to Cite
Manousaki, T., Feiner, N., Begemann, G., Meyer, A. and Kuraku, S. (2011), Co-orthology of Pax4 and Pax6 to the fly eyeless gene: molecular phylogenetic, comparative genomic, and embryological analyses. Evolution & Development, 13: 448–459. doi: 10.1111/j.1525-142X.2011.00502.x
- Issue published online: 20 SEP 2011
- Article first published online: 20 SEP 2011
- German Research Foundation (DFG). Grant Number: KU2669/1-1
- Konstanz Research School Chemical Biology. Grant Number: KoRS-CB
- International Max Planck Research School (IMPRS)
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.