Stripes and loss of color in ball pythons (Python regius) are associated with variants affecting endothelin signaling

Abstract

Color patterns in non-avian reptiles are beautifully diverse, but little is known about the genetics and development of these patterns. Here we investigated color patterning in pet ball pythons (Python regius), which have been bred to show color phenotypes that differ dramatically from the wildtype form. We report that several color phenotypes in pet animals are associated with putative loss-of-function variants in the gene encoding endothelin receptor EDNRB1: (i) frameshift variants in EDNRB1 are associated with conversion of the normal mottled color pattern to all-white skin (leucism), (ii) missense variants affecting conserved sites of the EDNRB1 protein are associated with dorsal, longitudinal stripes, and (iii) substitutions at EDNRB1 splice donors are associated with subtle changes in patterning compared to wildtype. We propose that these phenotypes are caused by loss of specialized color cells (chromatophores), with loss ranging from severe (leucism) to moderate (dorsal striping) to mild (subtle changes in patterning). Our study is the first to describe variants affecting endothelin signaling in a non-avian reptile and suggests that reductions in endothelin signaling in ball pythons can produce a variety of color phenotypes, depending on the degree of color cell loss.

Skin Ultrastructural Analysis Reveals a Lack of Iridophores in Adult Individuals of Differently-Colored Species of Galápagos Iguanas

“…This observation is interesting, as a black-striped pattern is visible in adult C. marthae, the only species of iguana in the Galápagos whose hatchlings present green areas in their skin. Recently, Dao and collaborators (40) showed that several color phenotypes in the snake Python regius, including dorsal striping, are associated with putative loss-of-function variants in the gene encoding endothelin receptor EDNRB2. Overall, these studies provide an important conceptual background for future investigation of the peculiar phenotypic color traits in the pink iguana.…”

A frameshift variant in the melanophilin gene is associated with loss of pigment from shed skin in ball pythons (Python regius)

“…An emerging model for genetic studies in reptiles is the ball python (P. regius) (Brown et al 2022;Garcia-Elfring et al 2023;Dao et al 2023). Ball pythons are native to west Africa, but have become common as pets.…”

“…Our approach was to collect samples of pet ball pythons (shed skins) from across the United States and search for putative loss-of-function variants in the melanophilin gene. A similar approach has been used previously by our group to identify variants controlling melanin production (Brown et al 2022) and patterning (Dao et al 2023).…”