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

Abstract

Pterin (also known as pteridine) pigments are responsible for many of the bright colours observed across the animal kingdom. Yet, unlike melanin, the genetics of pterin-based pigmentation has received relatively little attention in animal colouration studies. Here, we use a lineage of axanthic ball pythons (Python regius) found in captivity as a model system for studying pterin pigmentation in vertebrates. We crowd-sourced ball python shed skin from commercial breeders and applied a case-control study design. Using whole-genome pool sequencing (pool-seq) and variant annotation, we found a premature stop codon in GTP cyclohydrolase 1 (gch1) associated with the axanthic phenotype. The enzyme GCH1 plays a key role in pterin pigment biosynthesis as well as neurochemistry, catalyzing the first rate-limiting step of tetrahydrobiopterin (BH4) biosynthesis. Our work provides the first identification of an axanthism-associated gene in vertebrates and highlights the utility of ball pythons as a model system to study pterin-based pigmentation.