Metrics details. During embryogenesis, tight regulation of retinoic acid RA availability is fundamental for normal development. 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. 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.
Furthermore, comparisons of the regulatory regions of CYP26 genes of different bilaterian animals indicated that a CYPdriven negative feedback system was present in the last common ancestor of deuterostomes, but not in that of bilaterians. 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.
During animal development, the vitamin A-derived morphogen retinoic acid RA mediates a number of crucial functions, including, for example, early embryonic patterning and organogenesis, by acting on different cellular processes ranging from proliferation to cell death [ 1 — 7 ]. In vertebrates, normal development requires a very tightly controlled balance of the total amount of available RA, which is maintained through positive and negative feedback loops associated, respectively, with RA production chiefly by RALDH1, 2, and 3, for retinaldehyde dehydrogenase 1, 2, and 3 and RA degradation chiefly by CYP26A1, B1, and C1, for cytochrome P subfamily 26A1, B1, and C1 [ 8 — 12 ].
