Genetics of white color and iridophoroma in "Lemon Frost" leopard geckos

Coloration patterns promote survival and reproductive success in the animal kingdom. Despite their importance, wide gaps exist in our understanding of the genetic and evolutionary mechanisms that underpin them. The leopard gecko, Eublepharis macularius, is a popular companion animal, and displays a variety of coloration patterns. We investigated a spontaneous semi-dominant mutation, known as "Lemon Frost", that causes extensive white color in leopard gecko skin. Although "Lemon Frost" individuals are aesthetically appealing, more than 80% of them develop tumors of white color (i.e., iridophoroma) 0.5 to 5 years after birth. To identify the gene that regulates white color and is likely also responsible for the iridophoroma, we genotyped 220 animals, including 33 homozygous mutants, with short-read sequencing. We used synteny, linkage analysis and homozygosity mapping to localize the mutation to a strong candidate gene, SPINT1, a tumor suppressor previously implicated in human skin cutaneous melanoma (SKCM) as well as in over-proliferation of epithelial cells in mice and zebrafish. Our work establishes the leopard gecko as a tractable genetic system and suggests that a tumor suppressor in melanocytes in humans can also suppress tumor development in iridophores in lizards.