Repeated mutation of a developmental enhancer contributed to human thermoregulatory evolution
Daniel Aldea, Yuji Atsuta, Blerina Kokalari, S. F. Schaffner, Rexxi D. Prasasya, Adam Aharoni, Heather L. Dingwall, Bailey N. Warder, Yana G. Kamberov
Abstract
Significance One of the most distinctive physiological traits differentiating humans from other primates is a reliance on sweating to cool off. The effectiveness of human thermoregulatory sweating is underlain by the evolution of a dramatically increased density of water-secreting eccrine sweat glands in human skin relative to that of other primates. Here, we show that the accumulation of human-specific mutations in a developmental enhancer collectively promoted the production of eccrine glands in humans by up-regulating the expression of the Engrailed 1 transcription factor in the skin. This study reveals a mechanism that contributed to the evolution of humans’ signature thermoregulatory capabilities and underscores the importance of regulatory evolution in generating the modern human form.