Update of the keratin gene family: evolution, tissue-specific expression patterns, and relevance to clinical disorders

Human Genomics

Minh Ho¹  Christopher G. Bunick²  Vasilis Vasiliou³  Brian Thompson³  Daniel W. Nebert⁴  Elspeth A. Bruford⁵  Jeffrey Nicholas Fisk⁶ 

[1] Department of Dermatology, Yale University, PO Box 208059, 333 Cedar St., LCI 501, 06520-8059, New Haven, CT, USA;Department of Dermatology, Yale University, PO Box 208059, 333 Cedar St., LCI 501, 06520-8059, New Haven, CT, USA;Department of Molecular Biophysics and Biochemistry, Yale University, 06520, New Haven, CT, USA;Department of Environmental Health Sciences, Yale School of Public Health, 06511, New Haven, CT, USA;Departments of Pediatrics and Molecular and Developmental Biology, Cincinnati Children’s Research Center, 45229, Cincinnati, OH, USA;Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine, 45267, Cincinnati, OH, USA;HUGO Gene Nomenclature Committee (HGNC), EMBL-EBI, Wellcome Genome Campus, CB10 1SD, Hinxton, Cambridge, UK;Department of Haematology, University of Cambridge, CB2 0XY, Cambridge, UK;Program of Computational Biology and Bioinformatics, Yale University, 06511, New Haven, CT, USA;

关键词: Keratin;    Intermediate filament;    Evolutionary blooms;    Gene expression;    Gene duplications;    Synteny;    Markov-chain Monte Carlo (MCMC);    MrBayes program to estimate phylogeny;   

DOI  :  10.1186/s40246-021-00374-9

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY