En1 sweat we trust: How the evolution of an Engrailed 1 enhancer made humans the sweatiest ape
Abstract
Humans cool themselves primarily through the evaporation of water from the skin surface. Human eccrine sweat glands, which are responsible of secreting the water for evaporative cooling, are essential for this mechanism of thermoregulation [1]. Among primates, humans have the highest eccrine sweat gland density. Indeed, human eccrine sweat gland density is on average ten times that of chimpanzees and macaques [2]. The high density of eccrine glands in human skin is one of the most dramatic phenotypic differences that distinguishes humans from other primates, and is a key component that makes possible humans’ exceptional ability to cool off by sweating [1]. In spite of its importance, the genetic mechanisms behind the evolution of this adaptative human trait have been poorly studied. In our recent study [3], we identified the first genetic and developmental mechanism responsible for the evolutionary elaboration of human eccrine glands. Our study built on previous work from us and others showing that the upregulation of the transcription factor Engrailed 1 (En1) promotes the specification of eccrine glands in mice, and the upregulation of EN1 expression is correlated with eccrine gland development in humans [4,5]. We therefore sought to determine if humans have evolved regulatory mutations that lead to a potentiation of EN1 expression in the skin to induce the formation of more eccrine glands. Since the spatial pattern of En1 expression is conserved across mammals in regions…
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