Evolutionary relationships of CYP26 family members in zebrafish and mouse.

<p>(A) Phylogenetic analyses inferred by maximum likelihood (ML) indicate that Cyp26 paralogs of teleosts (i.e. zebrafish (Dre), medaka (Ola), stickleback (Gac) and fugu (Tru)) grouped with their correspondingly named Cyp26 paralogs of tetrapods (i.e. mouse (Mmu), human (Hsa) and chicken (Gga)). Numbers indicate bootstrap values supporting each node (n=100), and no significant differences were found between ML and NJ analyses. (B) A circleplot shows graphically orthologous relationships of <i>cyp26</i> genomic neighborhoods shared between zebrafish and mouse. Grey circumferential arcs represent chromosomes, with <i>Cyp26b1</i> in green on <i>Mmu</i>6, <i>Cyp26a1</i> in red on Mmu19, and <i>Cyp26c1</i> in blue on <i>Mmu</i>19. Colored lines link orthologous regions in zebrafish chromosomes <i>Dre</i>7, <i>Dre</i>12 and <i>Dre</i>17, the sites of <i>cyp26b1</i>, <i>cyp26a1</i> and <i>cyp26c1</i> genes, respectively. (C–E) Clusters of synteny conservation reveal the presence of many gene neighbor orthologs shared between each <i>Cyp26</i> genomic neighborhood in mouse and zebrafish <i>cyp26b1</i> (C: cluster ID#265419 according to the Synteny Database), <i>cyp26a1</i> (D: cluster ID#258723) and <i>cyp26c1</i> (E: cluster ID#265367). These results rule out the possibility of reciprocal gene losses in zebrafish and mouse that could mask actual orthologous relationships in artifactual phylogenetic trees, and provide strong support for the conclusion that the zebrafish/mouse gene pairs called <i>cyp26a1/Cyp26a1</i> and <i>cyp26b1/Cyp26b1</i> are in fact orthologs. F: Gene clusters of synteny conservation (cluster ID#191383) between <i>Dre12</i> and <i>Dre17</i> reveal that the genomic neighborhoods of <i>cyp26a1</i> and <i>cyp26c1</i> are paralogous due to the teleost genome duplication (TGD, R3) that preceded the divergence of the teleost lineage after it split from the tetrapod branch. Duplicates of <i>cyp26a1</i> and <i>cyp26c1</i> in <i>Dre</i>17 and <i>Dre</i>12 were lost reciprocally after the teleost genome duplication (labeled with crosses) in contrast to, for instance, <i>reep3</i> paralogs (in pink) that were maintained adjacent to <i>cyp26</i> paralogs.