Associations of MC1R Substitutions With Body Color Variation in a Desert Lizard

Body color variation is widespread among animals, and the melanocortin 1 receptor (MC1R) acts as a vital switch gene in regulating pigmentation. A small number of amino acid substitutions, or even a single one, in MC1R are known to influence the body coloration of animals. To investigate the associations between MC1R variants and body color variation in melanistic and non-melanistic populations of a toad-headed lizard, P. versicolor, we obtained the complete coding sequences of the MC1R gene. Sequence analysis identified two amino acid substitutions-V165I and V237I, located in transmembrane domains 4 (TM4) and 6 (TM6), respectively-that were significantly associated with color variation in P. versicolor. In silico structural analysis incorporating these two substitutions demonstrated that the melanistic MC1R exhibited stronger binding affinity for α-MSH, as characterized by a smaller binding surface area and volume, a greater number of hydrogen bonds, more favorable binding free energy, a higher binding constant, and a lower dissociation constant. These changes may ultimately enhance melanin synthesis in melanistic populations. Our results provide insights into how amino acid substitutions affect receptor-ligand-binding capacity by altering the pocket size of MC1R in P. versicolor.