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.

Filaggrin has evolved from an “S100 fused‐type protein” (SFTP) gene present in a common ancestor of amphibians and mammals

“…The presence of an S100 domain strongly suggests that SFTPs have evolved from an ancestral S100A gene. [1] As the central domains of SFTPs contain sequence repeats and short sequence motifs similar to those present in proteins encoded by other EDC-encoded proteins such as loricrin, [15,25] an origin of the primordial SFTP by "fusion" of different types of pre-existing EDC genes has been hypothesized. However, the absence of EDC genes other than S100As and SFTPs in frogs, which represent phylogenetically basal tetrapods, is more compatible with the alternative hypothesis that SFTPs have originated before other EDC genes.…”

“…[11][12][13] Our recent studies have suggested that SFTPs originated prior to the diversification of amniotes (mammals, reptiles and birds). [14][15][16] However, the evolutionary origin of SFTPs has remained uncertain because of incomplete genome data of the next relatives of amniotes, the amphibians. Here, we performed a comparative genomics study to infer the time of origin of SFTPs and to estimate when sequence elements of SFTPs, such as the carboxy-terminal motif implicated in binding keratin filaments, [14,17] have evolved.…”

Keratin: Structure, mechanical properties, occurrence in biological organisms, and efforts at bioinspiration

“…Keratins are also discussed in terms of mammalian keratin, reptilian keratin and avian keratin. Besides, studies on keratinization in vertebrates and the evolution of epidermal proteins have considered keratins as true keratin (a-keratin) and corneous beta-proteins (b-keratins) [33,34]. .…”

Review: mapping epidermal beta-protein distribution in the lizard Anolis carolinensis shows a specific localization for the formation of scales, pads, and claws

“…Different from the KAPs present in the other vertebrates, keratin-associated beta-proteins form themselves filaments and likely also interfilamentous matrix material (Brush 1983;Fraser and Parry 1996, 2011. These proteins and their genes are however unrelated to keratins of the intermediate filaments, and no phylogenetic study conducted so far has shown a molecular relationship between the two types Strasser et al 2014).…”

“…Therefore, all vertebrates, pisciform and terrestrial, produce filamentous keratins as a basic cytoskeletal framework to which KAPs or other corneous proteins (CPs) are later deposited as matrix material. It is believed that keratins of intermediate filaments originated before other corneous proteins and that the latter evolved later when the stratum corneum and different skin appendages evolved in relation to the formation of an EDC (Eckhart et al 2013;Strasser et al 2014). In sauropsids, among the other corneous proteins originated to form a stratum corneum, some possessed a betasheet region and were capable to form filaments (betakeratins) and not an amorphous matrix like other proteins.…”