135 Comparative genomics of skin barrier proteins reveals environment-dependent dispensability of the suprabasal epidermal keratins K1, K2, and K10

Abstract

The epidermis has been shaped by evolutionary adaptations to the environment. In humans, the most abundant proteins of the suprabasal epidermis are keratins K1, K2 and K10 which together form the cytoskeleton at the skin barrier. Mutations in K1 and K10 cause epidermolytic hyperkeratosis. Here, we performed comparative genomics to determine whether mutations in keratin genes were tolerated under different environmental constraints. Genome sequences of a phenotypically diverse set of mammalian species were screened by bioinformatic methods. The basal epidermal keratins K5 and K14 as well as the hyperproliferation-associated keratins K6 and K17 are highly conserved among mammals. By contrast, the late differentiation-associated keratin K2 has been lost in at least 4 phylogenetic lineages, indicating dispensability of K2 for skin barrier formation. K1 and K10 have been conserved in terrestrial mammals, but both have been inactivated in fully aquatic mammals of the phylogenetic clade comprising dolphins and whales. The results of this study identify specific components of the epidermal cytoskeleton that are associated with the skin barrier function in a terrestrial environment.