Evolution of an amphibian-specific family of epidermal differentiation-associated genes

The surface layer of the skin and hard skin appendages of land-dwelling vertebrates depend on epithelial differentiation-associated proteins which increase the mechanical resilience of cells upon cornification. These proteins, exemplified by keratin-associated proteins (KRTAPs) in mammals and epidermal differentiation complex (EDC) proteins in all tetrapods, have low amino acid sequence complexity and interact with other proteins to form stable supramolecular structures. No KRTAPs and only few EDC proteins exist in amphibians, suggesting an alternative mechanism of epithelial cornification. Here, we used comparative genomics and proteomics to identify a previously uncharacterized group of epidermal differentiation-associated proteins that are specific for amphibians. These proteins are encoded by genes of the amphibian epidermal differentiation cluster (AEDC), which has evolved by tandem duplications and sequence modifications of an ancestral gene at a locus syntenic with that of adipogenesis regulatory factor (ADIRF) in other vertebrates. AEDC genes are specifically expressed in the epithelium of the skin and its appendages such as the cornified spines within nuptial pads of frogs. Internal sequence duplications within AEDC proteins have led to amino acid sequence repeats similar to those of EDC proteins and KRTAPs. We conclude that epidermal differentiation-associated proteins have originated multiple times and evolved similar sequence features in amphibians and other clades of vertebrates.