Molecular evolution of the epidermis in amniotes

The epidermis of amniotes, i.e. mammals, reptiles and birds, establishes an essential barrier to the environment and forms important skin appendages such as hair. In the various evolutionary lineages of amniotes the epidermis has undergone adaptations to specific environments and lifestyles. By contrast, some structural principles such as the presence of a layer of cornified, dead cells, i.e. the stratum corneum, have been conserved. The formation and function of the epidermis is under the control of distinct genes, many of which (here referred to as "epidermis- associated genes") are expressed specifically during terminal differentiation of epidermal keratinocytes. The new availability of genome sequences from a broad range of amniotes including reptiles such as the anole lizard, birds such as the chicken and the zebra finch as well as mammals makes it possible, for the first time, to determine the genetic basis of the conservation of core elements of epidermal differentiation and of adaptations to a variety of lifestyles and environmental conditions. This study will investigate the evolution of the epidermis and epidermis- derived skin appendages of amniotes at the molecular level. The first aim is to develop an evolutionary scenario for the origin and adaptation of the complete set of epidermis-associated genes of humans. To this end, homologs of human genes with a epidermis-specific function will be identified in the genome sequences of other species and subsequently mapped onto the phylogenetic tree of amniotes. The second aim is to determine, in detail, the evolutionary history and functional diversification of (1) loricrin, i.e. the main protein of the cornified envelope, (2) filaggrin, i.e. the main keratin filament-aggregating protein, and (3) a novel cysteine-rich protein of reptiles. Gene expression studies and functional assays will be carried out in addition to phylogenetic analyses. The results of this first comprehensive characterization of the molecular evolution of the epidermis of amniotes will deepen our understanding of epidermal barrier formation and of genes implicated in human skin diseases.

The skin of mammals, reptiles and birds forms an essential barrier, which has adapted to different environments and lifestyles. This research project has yielded novel insights into the evolution of genes that regulate the barrier properties of human skin. In addition, important components of reptilian scales and avian feathers were identified. Finally, a novel scenario for the evolution the skin during the early phase of fully terrestrial life and during the diversification of amniotes was developed. The findings of this project are relevant for the evolutionary history of animals and for the characterization of the systems biology of human skin.The starting point of this project were genes that are known to be required for healthy skin in humans and which, upon mutation, are associated with atopic dermatitis, psoriasis and other skin diseases. Recently published genome sequence of numerous species of mammals, reptiles and birds were used to determine which human skin genes have equivalents (homologs) in other species. New variants of the gene encoding the skin barrier protein loricrin were found in birds and reptiles, indicating an evolutionary origin of this gene in a common ancestor that lived more than 300 million years ago. Similar results were obtained for filaggrin-type genes. The origin of these genes in ancestral terrestrial tetrapods and their conservation up to the present suggest important roles in the skin of amniotes. By contrast, homologs of other human skin genes are restricted to mammals, indicating that these genes contribute to features that distinguish mammalian from non-mammalian skin.A surprising result of this study was the discovery of a large number of protein components of reptilian skin, including new components of the turtle shell. Furthermore, we found a novel cysteine-rich protein which contributes to the mechanically resilient structure of feathers in birds. The results of this study have provided the basis for a follow-up project on the evolution of cornification proteins.