A Ball Python Colour Morph Implicates MC1R in Melanophore-Xanthophore Distribution and Pattern Formation

Reptiles showcase an extensive array of skin colours and patterns, yet little is known about the genetics of reptile colouration. Here, we investigate the genetic basis of the Clown colour morph found in captive-bred ball pythons (Python regius) to study skin pigmentation and patterning in snakes. We obtained samples by crowdsourcing shed skin from commercial breeders and hobbyists. We applied a case-control design, whole-genome pool sequencing, variant annotation, histological analyses, and electron microscopy imaging. We identified a missense mutation in a transmembrane region of the melanocortin-1 receptor (MC1R) associated with the Clown phenotype. In classic avian and mammalian model species, MC1R is known for controlling the type and amount of melanin produced. In contrast, our results suggest that MC1R signalling might play a key role in pattern formation in ball pythons, affecting xanthophore-melanophore distribution. This work highlights the varied functions of MC1R across different vertebrate lineages and promotes a novel model system to study reptile colouration.