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

Abstract Color patterns in nonavian 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 EDNRB2: (1) frameshift variants in EDNRB2 are associated with conversion of the normal mottled color pattern to skin that is almost fully white, (2) missense variants affecting conserved sites of the EDNRB2 protein are associated with dorsal, longitudinal stripes, and (3) substitutions at EDNRB2 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 (fully white) to moderate (dorsal striping) to mild (subtle changes in patterning). Our study is the first to describe variants affecting endothelin signaling in a nonavian 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. Pet ball pythons (Python regius) have been bred to exhibit color morphs that differ dramatically from the wildtype form. This study describes an allelic series of morphs that converts the normal mottled color pattern to stripes or all-white skin. The authors show that these morphs are associated with variants in an endothelin receptor gene. This study belongs to a course-based research experience for undergraduates and showcases the ability of undergraduates to contribute to real discoveries in a classroom setting.