The evolution of keratins was closely linked to the evolution of epithelia and epithelial appendages such as hair. The characterization of keratins in model species and recent comparative genomics studies have led to a comprehensive scenario for the evolution of keratins including the following key events. The primordial keratin gene originated as a member of the ancient gene family encoding intermediate filament proteins. Gene duplication and changes in the exon-intron structure led to the origin of type I and type II keratins which evolved further by nucleotide sequence modifications that affected both the amino acid sequences of the encoded proteins and the gene expression patterns. The diversification of keratins facilitated the emergence of new and epithelium type-specific properties of the cytoskeleton. In a common ancestor of reptiles, birds, and mammals, a rise in the number of cysteine residues facilitated extensive disulfide bond-mediated cross-linking of keratins in claws. Subsequently, these cysteine-rich keratins were co-opted for an additional function in epidermal follicular structures that evolved into hair, one of the key events in the evolution of mammals. Further diversification of keratins occurred during the evolution of the complex multi-layered organisation of hair follicles. Thus, together with the evolution of other structural proteins, epithelial patterning mechanisms, and development programmes, the evolution of keratins underlied the evolution of the mammalian integument.
Keywords: Claw; Cysteine; Epithelium; Evolution; Gene duplication; Hair; Molecular phylogenetics; Nail; Sequence motif; Tongue.