title: Evolutionary origin and diversification of epidermal barrier proteins in amniotes.
abstract: The evolution of amniotes has involved major molecular innovations in the epidermis. In particular, distinct structural proteins that undergo covalent cross-linking during cornification of keratinocytes facilitate the formation of mechanically resilient superficial cell layers and help to limit water loss to the environment. Special modes of cornification generate amniote-specific skin appendages such as claws, feathers, and hair. In mammals, many protein substrates of cornification are encoded by a cluster of genes, termed the epidermal differentiation complex (EDC). To provide a basis for hypotheses about the evolution of cornification proteins, we screened for homologs of the EDC in non-mammalian vertebrates. By comparative genomics, de novo gene prediction and gene expression analyses, we show that, in contrast to fish and amphibians, the chicken and the green anole lizard have EDC homologs comprising genes that are specifically expressed in the epidermis and in skin appendages. Our data suggest that an important component of the cornified protein envelope of mammalian keratinocytes, that is, loricrin, has originated in a common ancestor of modern amniotes, perhaps during the acquisition of a fully terrestrial lifestyle. Moreover, we provide evidence that the sauropsid-specific beta-keratins have evolved as a subclass of EDC genes. Based on the comprehensive characterization of the arrangement, exon-intron structures and conserved sequence elements of EDC genes, we propose new scenarios for the evolutionary origin of epidermal barrier proteins via fusion of neighboring S100A and peptidoglycan recognition protein genes, subsequent loss of exons and highly divergent sequence evolution.
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Strasser
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Mlitz
authors.affiliation: Department of Medical Biochemistry, Medical University of Vienna, Vienna, Austria.
authors.forename: Marcela
authors.initials: M
authors.lastname: Hermann
authors.affiliation: Department of Environmental Toxicology and Forensic Science Graduate Program, University of California-Davis.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Rice
authors.affiliation: Proteomics Core Facility, Genome Center, University of California-Davis.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Eigenheer
authors.affiliation: Dipartimento di Scienze Biologiche, Geologiche ed Ambientali (BiGeA), University of Bologna, Bologna, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Alibardi
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria leopold.eckhart@meduniwien.ac.at.
authors.forename: Leopold
authors.initials: L
authors.lastname: Eckhart
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D002645:Chickens / Q000235:genetics; D004817:Epidermis / Q000502:physiology; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D015603:Keratinocytes / Q000378:metabolism; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012104:Reptiles / Q000235:genetics; D030162:Reptilian Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D030161:Avian Proteins; D030162:Reptilian Proteins; D007633:Keratins
keywords: birds; epidermis; gene family; gene fusion; reptiles