Convergent Evolution of Cysteine-Rich Keratins in Horny Teeth of Jawless Vertebrates and in Cornified Skin Appendages of Amniotes

Cornified skin appendages, such as claws and hair, of amniotes consist of keratins with high numbers of cysteine residues, which serve as sites of protein cross-linking through disulfide bonds. Here, we show by proteomic analysis that cysteine-rich keratins are also components of the horny teeth of the sea lamprey (Petromyzon marinus), a jawless vertebrate. The cysteine-rich keratins of the lamprey are conserved in hagfish, which diverged from lampreys around 460 million years ago. Phylogenetic analysis confirmed the orthology of the cysteine-rich keratins of lampreys and hagfish (cyclostomes) and showed that cysteine-rich keratins of amniotes belong to different clades of keratins. We conclude that keratins with elevated cysteine content evolved not only in amniotes but also, and much earlier, in jawless vertebrates. The convergent evolution of a high abundance of cysteine residues is in line with a critical role of intermolecular disulfide bonds in hard epithelial structures of vertebrates.