A role for orange pigments in birds and human redheads

PNAS Nexus

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Male (left) and female (right) zebra finches. The orange feathers displayed by the male are colored by the pigment pheomelanin, which is also present in human skin and red hair. Pheomelanin is associated with an increased risk of melanoma, but also exerts a beneficial physiological function consisting in the avoidance of toxicity that an excess of the amino acid cysteine in the diet may cause. Female zebra finches, which do not produce pheomelanin like males, experience cellular damage when exposed to high dietary levels of cysteine.

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Credit: Ismael Galván

A pigment that makes feathers and hair orange helps prevent cellular damage by removing excess cysteine from cells. Pheomelanin is an orange-to-red pigment that is built with the amino acid cysteine and found in human red hair and fair skin, as well as in bird feathers. Previous research has shown that pheomelanin is associated with increased melanoma risk, raising questions about why evolution has maintained genetic variants that promote pheomelanin production. Ismael Galván and colleagues studied 65 adult zebra finches divided into treatment and control groups. In the treatment group, male zebra finches received dietary cysteine and ML349, a drug that blocks pheomelanin synthesis. Male birds treated with both cysteine and ML349 showed increased oxidative damage in blood plasma compared to males receiving only cysteine, when the authors controlled for overall expression of the regulator of antioxidants by melanocytes. Female birds, which do not produce pheomelanin, tended to show increased oxidative damage when treated with cysteine alone as compared to female controls. According to the authors, pheomelanin synthesis helps maintain cysteine homeostasis by converting excess cysteine into inert pigment, which may explain why pheomelanin-promoting genetic variants persist despite being associated with increased melanoma risk.

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Journal

PNAS Nexus

Article Title

MC1R depalmitoylation inhibition reveals a physiological role for pheomelanin

Article Publication Date

6-Jan-2026