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Background  During embryogenesis, tight regulation of retinoic acid (RA) availability is fundamental for normal development. In parallel to RA synthesis, a negative feedback loop controlled by RA catabolizing enzymes of the cytochrome P450 subfamily 26 (CYP26) is crucial. In vertebrates, the functions of the three CYP26 enzymes (CYP26A1, CYP26B1, and CYP26C1) have been well characterized. By contrast, outside vertebrates, little is known about CYP26 complements and their biological roles. In an effort to characterize the evolutionary diversification of RA catabolism, we studied the  CYP26  genes of the cephalochordate amphioxus ( Branchiostoma lanceolatum ), a basal chordate with a vertebrate-like genome that has not undergone the massive, large-scale duplications of vertebrates.    Results  In the present study, we found that amphioxus also possess three  CYP26  genes ( CYP26-1 ,  CYP26 -2, and  CYP26-3 ) that are clustered in the genome and originated by lineage-specific duplication. The amphioxus  CYP26  cluster thus represents a useful model to assess adaptive evolutionary changes of the RA signaling system following gene duplication. The characterization of amphioxus  CYP26  expression, function, and regulation by RA signaling demonstrated that, despite the independent origins of  CYP26  duplicates in amphioxus and vertebrates, they convergently assume two main roles during development: RA-dependent patterning and protection against fluctuations of RA levels. Our analysis suggested that in amphioxus RA-dependent patterning is sustained by CYP26-2, while RA homeostasis is mediated by CYP26-1 and CYP26-3. Furthermore, comparisons of the regulatory regions of  CYP26  genes of different bilaterian animals indicated that a CYP26-driven negative feedback system was present in the last common ancestor of deuterostomes, but not in that of bilaterians.    Conclusions  Altogether, this work reveals the evolutionary origins of the RA-dependent regulation of  CYP26  genes and highlights convergent functions for CYP26 enzymes that originated by independent duplication events, hence establishing a novel selective mechanism for the genomic retention of gene duplicates.    Electronic supplementary material  The online version of this article (doi:10.1186/s12862-016-0863-1) contains supplementary material, which is available to authorized users.

bmc evolutionary biology

Lineage-specific duplication of amphioxus retinoic acid degrading enzymes (CYP26) resulted in sub-functionalization of patterning and homeostatic roles