GTP cyclohydrolase II (gch2) and axanthism in ball pythons: A new vertebrate model for pterin-based pigmentation

Pterin pigments are responsible for many of the bright colors observed across the animal kingdom. However, unlike melanin, the genetics of pterin-based pigmentation has received relatively little attention in animal coloration studies. Here, we investigate a lineage of axanthic ball pythons (Python regius) found in captivity as a model system to study pterin pigmentation in vertebrates. By crowdsourcing shed skin samples from commercial breeders and applying a case-control study design, we used whole-genome pool sequencing (pool-seq) and variant annotation. We identified a premature stop codon in the gene GTP cyclohydrolase II (gch2), which is associated with the axanthic phenotype. GCH2 catalyzes the first rate-limiting step in riboflavin biosynthesis. This study provides the first identification of an axanthism-associated gene in vertebrates and highlights the utility of ball pythons as a model to study pterin-based pigmentation.