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Molecular Biology and Evolution, Vol 5, 97-108, Copyright © 1988 by Society for Molecular Biology and Evolution

ORIGINAL ARTICLE

Inactivation of human keratin genes: the spectrum of mutations in the sequence of an acidic keratin pseudogene

ES Savtchenko, IM Freedberg, IY Choi and M Blumenberg
Department of Dermatology, New York University Medical Center, New York 10016.

Keratins are cytoskeletal proteins encoded by a multigene family. We have identified the first human keratin pseudogene and determined its complete nucleotide sequence. Sequence comparisons indicate that the pseudogene arose from a very recent duplication of the 50-kd keratin (K14) gene. The coding and the intron sequences of the two genes are 95% and 93% identical, respectively. Although the sequence of the regulatory region in the pseudogene is virtually identical to that in the 50-kd functional gene, several deleterious mutations have been identified in the pseudogene. There are three frameshifts in the coding regions, one of which is a perfect 8-bp duplication. A single-base-pair deletion in the first exon and a single-base-pair insertion in the penultimate exon also result in frameshifts. The three remaining deleterious mutations interfere with the mRNA processing signals: two alter the intron/exon boundaries, and the third disrupts the polyadenylation signal. These mutations clearly identify the sequence as a human keratin pseudogene.
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