The Origin And Evolution Of RPE65
RPE65 is a protein expressed at high levels in vertebrate retinal pigment epithelium, and has recently been revealed as the isomerohydrolase of the vertebrate visual cycle (Jin, Li, et al., Cell 122:449-59 2005). RPE65 is a member of the carotenoid oxygenase family, proteins that typically cleave and oxygenate carotenoids along their polyene backbone. The other family members in vertebrates are BCO1 and BCO2, which cleave beta-carotene at the 15-15' and 9-10 positions respectively.
Carotenoid oxygenase genes are found in insects and C. elegans, althoguh sequence relationships suggest they are more distantly related than BCO1, BCO2 and RPE65 are to each other. A number of other, more distant, family members are known from plants, e.g VP14, important in the synthesis of abscissic acid; fungi; and bacteria, including lignostilbene dioxygenase, which cleaves lignostilbene rather than a carotenoid. RPE65 is the only member of this family known to catalyse an isomerase reaction rather than a cleavage/oxygenase reaction.
As the visual cycle appears to be specific to vertebrates, and possibly related to the development of night vision and rods, the origin and evolutionary relationships of RPE65 are of interest. Thus, we investigated the carotenoid oxygenase gene representation in vertebrates and Ciona intestinalis, a relatively close relative of vertebrates, whose genome has recently been sequenced.
It appears that the Ciona genome contains two members of this gene family, one corresponding to the vertebrate BCO1, and the other to the common ancestor of RPE65 and BCO2. We provide evidence that this second gene is more likely to have a BCO2-like function. All vertebrates appear to have all three genes, suggesting that the Ciona-like gene duplicated early in vertebrate evolution, corresponding to the origin of the vertebrate visual cycle. Furthermore, after rapid initial divergence, RPE65 is evolving more slowly than BCO1 and BCO2, throwing further light on the unusual functionality of RPE65.