Evolution and complexity of the genes encoding the keratins of human epidermal cells

Abstract

The keratins are a family of proteins (M(r) = 40-70 K) that form 8-nm intermediate filaments in the cytoplasm of most vertebrate epithelial cells. Each epithelial cell expresses its own subset of keratins, which consists of about 2 to 5 polypeptides. In epidermis, the keratins are especially abundant, comprising 30 to 85 percent of the total protein of these cells. Four major keratins (M(r) = 46, 50, 56, and 58 K) are expressed in the basal cells, whereas the larger keratins (60-70 K) are found only in differentiating epidermal cells. We have shown that in human epidermis there are multiple mRNAs for the keratins. These RNAs can be grouped into two distinct classes as judged by their ability to hybridize to one of two separate classes of cloned keratin cDNA sequences. Each of these two classes of sequences is encoded by a multigene family of about 10 genes each, and these two families are coordinately conserved throughout vertebrate evolution. Recently, we have determined the DNA sequence of a cloned cDNA insert that is complementary to greater than 90 percent of the coding region for the 50 K keratin and which shares homology with 46 K keratin mRNA. A comparison of the predicted amino acid sequence of this cytoskeletal keratin with partial sequences of keratins of epidermal appendages, e.g., wool, shows that there is a distinct relation with the fibrous keratins of wool, but little or no relation with the matrix keratins. A comparison of the 50 K keratin sequence with the partial sequences known for other intermediate-filament proteins indicates that the keratins may be the most distantly related of this class of 80- to 100-A filamentous proteins. This is in contrast to the actins and tubulins, which are highly conserved components of vertebrate cytoskeletons. The wide flexibility in the amino acid sequence of intermediate filament proteins suggests that these proteins have evolved to meet subtly different requirements in the cytoskeletal architecture.