a, anole; c, chicken; h, human; m, mouse. aHAS1 through aHAS4 and cHAS1 and cHAS2 Cloflubicyne formed a cluster that was separated from the branch leading to mammalian type I hair keratins and aHA1 and aHA2 (Fig. identified a novel group of reptilian cysteine-rich type I keratins that lack homologues in mammals. Our data show that cysteine-rich CR1 -keratins are not restricted to mammals and suggest that the evolution of mammalian hair involved the co-option of pre-existing structural proteins. Keywords:cytokeratin, epidermis, evolution, reptiles, claw One of the key steps in mammalian evolution was the emergence of hair, which served in protection from mechanical insults and also facilitated homeothermy (1,2). Because hair is a defining feature of mammals and does not occur in other amniotes, it seems to have evolved after divergence of the therapsid lineage (leading to mammals) from the sauropsid lineage (reptiles, birds) approximately 310 to 330 million years ago (3). It has been proposed that hair originated by modification of scales (46); however, there is no paleontologic evidence for intermediate forms. The main constituents of the hair shaft are the hair keratins and keratin-associated proteins. Hair keratins belong to the protein families of the type I (acidic) and type II (basic) -keratins, with diverse members that are expressed in a wide variety of epithelia. Type I and type II keratins heterodimerize by coiled-coil formation of their -helical central domains. The resulting dimers establish higher-order structures via hydrophobic and ionic interactions and ultimately form intermediate filaments (7). In contrast to soft keratins, hair keratins contain numerous cysteine residues, which are used for intermolecular disulfide bond formation during hardening of the hair shaft (8). Hair keratin genes are nested within the type I and type II keratin gene clusters in the genomes of humans (type I keratin genes on chromosomes 17q21.2 and type II keratin genes as well as KRT18 on chromosome 12q13.13) and other mammals. The human genome contains 11 hair-type and 17 other type I keratins, as well as 6 hair-type and 20 other type II keratin genes (9). All hair keratins are expressed Cloflubicyne in the hair shaft, and some are also expressed in claws and nails, on the keratinized surface of the tongue, and within Hassall’s bodies of the thymus (10,11). The critical role in hair biology of hair keratins is revealed by the fact that mutations in single hair keratin genes suffice to cause the inherited hair fragility and alopecia syndrome monilethrix (12,13). Supporting a mammal-specific origin of hair, hair keratin genes have been reported to be absent from chicken and other nonmammalian species (14,15). So-called -keratins, a family of sauropsid-specific proteins structurally unrelated to -keratins but similar to mammalian keratin-associated proteins (16,17), are the main components of hard integumentary structures (scales, claws, beaks, feathers) of sauropsids. However, the role of -keratins in sauropsid epidermis and epidermal appendages has not been explored in depth. Here we performed a comparative genomics analysis to screen for new homologues of hair keratins in amniotes. We identified nonmammalian homologues of Cloflubicyne hair keratins in the newly available, unannotated draft genome sequence of the reptileAnolis carolinensis(green anole lizard) and a hard keratin gene orthologue of the chicken. In addition, we identified a group of sauropsid-specific cysteine-rich type I keratins. Our data suggest a nonmammalian origin of the main structural proteins of hair and, therefore, require a revision of the current concept of hair evolution. == Results == == Identification of Nonmammalian Hair Keratin-like Genes. == The keratin gene clusters of the anole and chicken were analyzed for the presence of orthologues of mammalian hair keratins. The keratin genes flanking the human hair keratins (KRT23 and KRT13/KRT15 at the type I keratin gene locus, as well as KRT7 and KRT75 at the type II keratin gene locus) were conserved and defined the borders of the hair keratin loci in all species investigated (Fig. 1). Six putative orthologues of mammalian hair keratins were identified in the anole genome and one orthologue in chicken. The novelA. carolinensisgenes encoded two type I keratins, tentatively named aHA1 and aHA2 (for anole hard acidic keratins 1 and 2), which were most similar in sequence to keratin 36, and four type II keratins, tentatively named aHB1 through aHB4 (for anole hard basic keratins 1 through 4), which were most similar in sequence to keratins 84 among human keratins. The sequences of all new keratins, sequence alignments with human keratins, and sequence similarities among hard keratins are provided insupporting information (SI) Figs. S1S3andTables S1S4. == Fig. 1. == Comparison of.
Categories:FFA1 Receptors