Ancient lineages of the keratin-associated protein (KRTAP) genes and their co-option in the evolution of the hair follicle.

BLAST searches against the human genome showed that of the 93 keratin-associated proteins (KRTAPs) of Homo sapiens, 53 can be linked by sequence similarity to an H. sapiens metallothionein and 16 others can be linked similarly to occludin, while the remaining KRTAPs can themselves be linked to one or other of those 69 directly-linked proteins. The metallothionein-linked KRTAPs comprise the high-sulphur and ultrahigh-sulphur KRTAPs and are larger than the occludin-linked set, which includes the tyrosine- and glycine-containing KRTAPs. KRTAPs linked to metallothionein appeared in increasing numbers as evolution advanced from the deuterostomia, where KRTAP-like proteins with strong sequence similarity to their mammalian congeners were found in a sea anemone and a starfish. Those linked to occludins arose only with the later-evolved mollusca, where a KRTAP homologous with its mammalian congener was found in snails. The presence of antecedents of the mammalian KRTAPs in a starfish, a sea anemone, snails, fish, amphibia, reptiles and birds, all of them animals that lack hair, suggests that some KRTAPs may have a physiological role beyond that of determining the characteristics of hair fibres. We suggest that homologues of these KRTAPs found in non-hairy animals were co-opted by placodes, formed by the ectodysplasin pathway, to produce the first hair-producing cells, the trichocytes of the hair follicles.