Schneider A, David VA, Johnson WE, et al. How the leopard hides its spots: ASIP mutations and melanism in wild cats. PLoS ONE. 2012; 7: e50386. (free, full text article)
Melanism (dark-colored pigmentation in the skin or pelage) is common in the cat family (Felidae), being reported in 13 of 37 extant felid species. Melanism can reach high frequencies in some cat species, e.g., Panthera pardus a.k.a. black leopard and Pardofelis temminckii a.k.a. Asian golden cat, suggesting this phenotype may be adaptive. However, little is known about the evolutionary history and ecological/behavioral significance of melanism in any felid. Two different genes whose products interact in the regulation of melanin production influence felid melanism. Melanocortin-1 receptor (MC1R) activation by binding alpha melanocyte stimulating hormone leads to eumelanin (dark pigment) synthesis. In contrast, binding the agouti signalling protein (ASIP) can inhibit MC1R activation, which causes a switch to pheomelanin (light pigment) synthesis.
In this study, DNA analysis of blood or skin samples from P. pardus and P. temminckii collected from captive animals of Asian origin identified two different variants of the ASIP gene implicated in melanistic phenotype. Experiments revealed that non-synonymous mutations involving any of 10 cysteine residues of the C-terminal Cys-rich domain adversely affected ASIP activity, suggesting these residues are critical for protein activity and receptor binding to MC1R. In P. temminckii, a change in the 9th normally conserved cysteine residue to tryptophan led to melanism. In P. pardus, a mutation was identified that led to the elimination of most of the C-terminal domain from the 4th normally conserved cysteine onward. Identification of these two novel mutations associated with melanism in wild felids, taken together with three previously reported mutations in either MC1R or ASIP, leads to the conclusion that this mutant phenotype arose at least five times independently in the cat family. Interestingly, three of these mutations are located in ASIP, suggesting that this gene is equally or more often involved in felid melanism than MC1R. [GO]