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

Tong, H ORCID: 0000-0002-7094-2832, Lin, Q, Shi, S, Wang, K ORCID: 0009-0000-1207-6254, Guo, Y, Brown, RP ORCID: 0000-0003-2401-6077 and Jin, Y ORCID: 0000-0002-1001-2158 (2026) Associations of MC1R Substitutions With Body Color Variation in a Desert Lizard. Ecology and Evolution, 16 (4). ISSN 2045-7758

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	3109 Zoology; 31 Biological Sciences; 0602 Ecology; 0603 Evolutionary Biology; 3103 Ecology; 3104 Evolutionary biology; 4102 Ecological applications
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics Q Science > QL Zoology
Divisions:	Biological and Environmental Sciences (from Sep 19)
Publisher:	Wiley
Date of acceptance:	31 March 2026
Date of first compliant Open Access:	7 May 2026
Date Deposited:	07 May 2026 11:46
Last Modified:	07 May 2026 11:46
DOI or ID number:	10.1002/ece3.73481
URI:	https://researchonline.ljmu.ac.uk/id/eprint/28533

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