iScience 2025 Aug 19;289:113369. doi: 10.1016/j.isci.2025.113369.

Evolutionary adaptations of TRPA1 thermosensitivity and skin thermoregulation in vertebrates.

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Skin pigmentation contributes to thermoregulation in ectothermic vertebrates, while homeotherms rely on insulation such as feathers, fur, or blubber. Heat-sensing in vertebrates largely depends on transient receptor potential (TRP) channels, with TRPA1 showing evolutionary shifts in sensitivity. The exploration of a role for TRP channels in skin physiology has largely focused on human pigmentation and overlooked the evolution of different thermoregulatory structures in the integument of distinct vertebrates. We investigated heat-induced skin darkening in the ectotherm Xenopus laevis and found TRPA1 mediates melanosome dispersion. Conversely, TRPA1 mediates cold sensation in rodents and UV-induced tanning in humans. In Euarchontoglires, a switch to TRPA1 cold thermal sensitivity correlates with a change in an essential amino acid (V→G878). Aquatic mammals (manatees, whales) that rely on blubber for insulation show reduced TRPA1 selection pressure as compared to their terrestrial relatives. Our findings highlight TRPA1's adaptive evolution across vertebrates, linking thermal sensing to integumentary specialization.

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