Abstract
Intermediate filament (IntFil) genes arose during early metazoan evolution, to provide mechanical support for plasma membranes contacting/interacting with other cells and the extracellular matrix. Keratin genes comprise the largest subset of IntFil genes. Whereas the first keratin gene appeared in sponge, and three genes in arthropods, more rapid increases in keratin genes occurred in lungfish and amphibian genomes, concomitant with land animal-sea animal divergence (~ 440 to 410 million years ago). Human, mouse and zebrafish genomes contain 18, 17 and 24 non-keratin IntFil genes, respectively. Human has 27 of 28 type I “acidic” keratin genes clustered at chromosome (Chr) 17q21.2, and all 26 type II “basic” keratin genes clustered at Chr 12q13.13. Mouse has 27 of 28 type I keratin genes clustered on Chr 11, and all 26 type II clustered on Chr 15. Zebrafish has 18 type I keratin genes scattered on five chromosomes, and 3 type II keratin genes on two chromosomes. Types I and II keratin clusters—reflecting evolutionary blooms of keratin genes along one chromosomal segment—are found in all land animal genomes examined, but not fishes; such rapid gene expansions likely reflect sudden requirements for many novel paralogous proteins having divergent functions to enhance species survival following sea-to-land transition. Using data from the Genotype-Tissue Expression (GTEx) project, tissue-specific keratin expression throughout the human body was reconstructed. Clustering of gene expression patterns revealed similarities in tissue-specific expression patterns for previously described “keratin pairs” (i.e., KRT1/KRT10, KRT8/KRT18, KRT5/KRT14, KRT6/KRT16 and KRT6/KRT17 proteins). The ClinVar database currently lists 26 human disease-causing variants within the various domains of keratin proteins.
Highlights
Evolutionary expansion of keratin genes Keratins were the first group of intermediate filament (IntFil) to have their X-ray diffraction pattern discovered [1]
We created phylogenetic trees for type I and type II keratin proteins from a broad representation of animal species (Fig. 5). These data suggest that the clade containing the KRT18 and the KRT80 and KRT8 proteins is least divergent from the ancient IntFil protein lamin, and most closely resembles precursors for the other members of the keratin group
With respect to posttranslational keratin filament assembly, we know that discrete molecular interactions can regulate higher-order keratin structures
Summary
Intermediate filaments: historical background By end of the Cambrian explosion (~ 500 million years ago), intermediate filament (IntFil) genes had become well established in the Animalia Kingdom and began expanding rapidly, encoding novel proteins that were. In contrast to vimentin, for keratins both longitudinal and lateral filament assembly apparently happen concomitantly These assembly mechanisms were proposed, based on data from negative-stain electron microscopy studies which characterized the in vitro formation of keratins, lamin, and vimentin under physiological conditions [20,21,22]. This forms the major interface between heterodimers in the tetrameric complex [16]; this hydrophobic interface contains a “knob-pocket tetramerization mechanism” on the type II keratin, which is key for driving the A 11 tetrameric alignment This interface between heterodimers is crucial for mature IntFil assembly, as demonstrated by an in vitro study of mutations in type II keratin proteins, which resulted in defective IntFil formation [16]. We direct the readers to other informative reviews for a thorough discussion of types III [28], IV [29], V [30] and VI [31] IntFil families
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