Physiological plasticity in zebra finch color varieties mitigates DNA damage under oxidative stress

Melanins are fundamental vertebrate pigments. Pheomelanin synthesis utilizes cysteine, a precursor for the antioxidant glutathione. Sustained pheomelanin synthesis may thus reduce cysteine availability for antioxidant defenses, resulting in a trade-off most relevant in stressful environments. Here, we investigated how pheomelanin may influence birds' response to oxidative stress. We began by determining the genetic bases of three independent melanin-based zebra finch varieties. Two previously established melanin genes can explain <i>blackcheek</i> (<i>NDP</i>) and <i>white</i> (<i>EDNRB2</i>) mutations, while a novel pigmentation gene (<i>ZNRF3</i>) was associated with the eumelanin-to-pheomelanin shift in the <i>orange-breasted</i> phenotype. <i>Orange-breasted</i> individuals exhibited higher DNA damage and a gene expression profile compatible with cellular redox imbalance. During oxidative stress, these birds minimized DNA damage and changed pheomelanin concentration, consistent with cysteine/glutathione economization. Further analyses revealed downregulation of glutathione S-transferases in pheomelanic morphs across species. We propose that pheomelanic birds might have an adaptive built-in physiological plasticity under environmental oxidative stress.