HDL receptor/Scavenger receptor B1-Scarb1 and Scarb1-like mediate the carotenoid-based red coloration in fish

Both carotenoids and pteridine pigments can produce colors ranging from red to yellow and participate in mate choice, antioxidant, and immunity processes in animals. Common carp (Cyprinus carpio) variants with red coloration have been selectively bred for more than a thousand years, yet the mechanism that regulates coloration remains poorly understood. Here we provided experimental evidence that the red coloration in common carp varieties was carotenoid-based and was regulated by the carotenoid transport genes Scarb1 and Scarb1-like (high density lipoprotein (HDL) receptor/ scavenger receptor B type 1, also known as SR-BI). We found that carotenoids rather than pteridine pigments were specific to whole red (WR) but absent in whole white (WW) Oujiang color common carp (Cyprinus carpio var. color). Scarb1 and its novel paralog gene Scarb1-like were the most significant carotenoid metabolism-related genes differentially expressed between WR and WW, whereas no difference was detected for the Gch1 (GTP cyclohydrolase 1) gene, which acted as a rate limiting enzyme in the pteridine pathway. Disruption of Scarb1, Scarb1-like, and Gch1 using CRISPR/Cas9 technology resulted in regional red skin fading into white color in Scarb1 and Scarb1-like mutated WR (S^+/−), leading to a decrease and a complete loss of astaxanthin and lutein in the red and white areas, respectively. However, no skin color variations were observed in Gch1 mutated WR fishes. In addition, disruption of the two Scarb1 genes and Gch1 together in WR caused red color variations similar to those observed in S^+/− WR. Finally, carotenoids supplementation recovered the red color but had poorly effects on the white color in S^+/− WR. This study revealed a plausible molecular mechanism responsible for red and white body colors and may benefit selective breeding programs of ornamental and cultured fish.