Retinoic acid production via the ray-finned fish gene beta-carotene oxygenase 1-like is essential for juvenile development

In vertebrates, vitamin A (VA) is crucial for development, tissue homeostasis, vision, and immunity. Retinal, a form of VA, is produced via enzymatic cleavage of β-carotene by beta-carotene oxygenase 1 ( bco1 ) and bco1-like ( bco1l ). While bco1 is found across vertebrate taxa, bco1l is a paralog of bco1 that we discover to have evolved in the ray-finned fishes, the most abundant, speciose, and commercially important group of fishes. We investigated the function of bco1l in ray-finned Siamese fighting fish, commonly known as betta, an emerging model for genetics and development. Using CRISPR-Cas9 knockouts, we find that lack of bco1l results in reduced VA and elevated β-carotene in larvae, starting when animals have exhausted their yolk supply of retinal, followed by stunted growth and death during juvenile development. Exogenous retinoic acid rescues the mutation, demonstrating its deficiency causes these defects. bco1l is 4× more abundant than bco1 in the intestine. This, coupled with the inability of bco1 to sustain VA production in the bco1l mutant, indicates that bco1l is the primary enzyme for dietary carotenoid conversion into retinal. Our results show that VA production by bco1l is required for post-embryonic development, and that bco1l became essential after evolving via duplication of bco1 .