Independent Mutations in the LRP2 Gene Mediating Telescope Eyes and Celestial Eyes in Goldfish

After intensive artificial selection, the development of celestial eyes in goldfish involves the eyeballs protuberating and turning upwards. Thus, the celestial eye goldfish is an excellent model for both evolutionary and human ocular disease studies. Here, two mapping populations of goldfish with segregating eye phenotypes in the offspring were constructed. Through whole-genome sequencing and RNA-seq for eyeball samples, a premature stop codon in Exon 38 of the <i>LRP2</i> gene was identified as the top candidate mutation for the celestial eye in goldfish. Fatty acid metabolism and epidermal cells, especially keratocyte-related functions, were inhibited in the eyeballs of celestial eye goldfish, while inflammatory reactions and extracellular matrix secretions were stimulated. These results suggest the dysfunction of the cornea in the celestial eye goldfish, and the same for the retina, which could be the results of the truncated LRP2 protein. In addition, the same gene, <i>LRP2</i>, is in charge of similar phenotypes (celestial eye and telescope eye) in goldfish, but these phenotypes have no shared mutations. In conclusion, the candidate mutation for the celestial eye in goldfish was identified by this study for the first time, and parallel evolutions of similar phenotypes at the molecular level under artificial selection were observed. These findings provide insights into the developmental and evolutionary processes of morphological changes in the eyes of goldfish.