2 / 2016-03-18 23:32:56

New insights into skin barrier evolution: origin and selection of the filaggrin-like proteins

9594,9595,9596

Mammals have evolved various structural adaptations that allow them to survive better in challenged environments. The adaptation history of the epidermis is modulated to maintain the skin homeostatic barrier function. Filaggrin is a key protein that facilitates formation of the skin barrier. Skin barrier defects caused by filaggrin mutations have been shown to be major predisposing factors for atopic dermatitis. There is little knowledge, however, on the molecular mechanisms underlying epidermal evolution. Here we provide molecular evidences for supporting that epidermal adaptation is a process of natural selection. We first provided a complete identification of the S100-fused-type-protein (SFTP) gene family in humans and mice, including filaggrin, trichohyalin, cornulin, hornerin, filaggrin-2, repetin and trichohyalin-like 1. These genes are closely clustered within the epidermal differentiation complex at human 1q21 and share a conserved gene and protein structure. We found that they are all expressed in the human and mouse skin but are selectively expressed in other less-complex epithelial tissues examined. Secondly, we determined all SFTP orthologs in other vertebrates including fish, frog and chicken. We show that the SFTP family members follow a conserved one-to-one orthologous relationship in mammals while there is only one member (cornulin) in frogs, suggesting that the SFTP family may stem from gene duplication of a cornulin ancestor in a common mammalian ancestor after mammal-bird split (∼200–310 million years ago). These data are not compatible with the previous hypothesis of filaggrin present in all non-mammals. Finally, examining the pattern of evolutionary change in this gene family, we uncovered the signatures of positive selection in three filaggrin-like SFTP members, which are confined to the repeat-containing domain, suggesting a process of natural selection. Together, our data indicate that the adaptation history of mammal epidermis is coincided with the origin and natural selection of the filaggrin-like proteins and may help us understand the functional evolution of skin barrier.