Regulatory changes in pterin and carotenoid genes underlie balanced color polymorphisms in the wall lizard

Abstract

Significance Reptiles show an amazing color diversity based on variation in melanins, carotenoids, and pterins. This study reveals genes controlling differences between three color morphs (white, orange, and yellow) in the common wall lizard. Orange pigmentation, due to high levels of orange/red pterins in skin, is caused by genetic changes in the sepiapterin reductase gene. Yellow skin, showing high levels of yellow carotenoids, is controlled by the beta-carotene oxygenase 2 locus. Thus, the color polymorphism in the common wall lizard is associated with changes in two small regions of the genome containing genes with crucial roles in pterin and carotenoid metabolism. These genes are likely to have pleiotropic effects on behavior and other traits associated with the different color morphs. Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors. These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard (Podarcis muralis), which differ in orange and yellow pigmentation and in their ecology and behavior, are virtually undifferentiated. Genetic differences are restricted to two small regulatory regions near genes associated with pterin [sepiapterin reductase (SPR)] and carotenoid [beta-carotene oxygenase 2 (BCO2)] metabolism, demonstrating that a core gene in the housekeeping pathway of pterin biosynthesis has been coopted for bright coloration in reptiles and indicating that these loci exert pleiotropic effects on other aspects of physiology. Pigmentation differences are explained by extremely divergent alleles, and haplotype analysis revealed abundant transspecific allele sharing with other lacertids exhibiting color polymorphisms. The evolution of these conspicuous color ornaments is the result of ancient genetic variation and cross-species hybridization.