A curated catalog of canine and equine keratin genes

Abstract

Keratins represent a large protein family with essential structural and functional roles in epithelial cells of skin, hair follicles, and other organs. During evolution the genes encoding keratins have undergone multiple rounds of duplication and humans have two clusters with a total of 55 functional keratin genes in their genomes. Due to the high similarity between different keratin paralogs and species-specific differences in gene content, the currently available keratin gene annotation in species with draft genome assemblies such as dog and horse is still imperfect. We compared the National Center for Biotechnology Information (NCBI) (dog annotation release 103, horse annotation release 101) and Ensembl (release 87) gene predictions for the canine and equine keratin gene clusters to RNA-seq data that were generated from adult skin of five dogs and two horses and from adult hair follicle tissue of one dog. Taking into consideration the knowledge on the conserved exon/intron structure of keratin genes, we annotated 61 putatively functional keratin genes in both the dog and horse, respectively. Subsequently, curators in the RefSeq group at NCBI reviewed their annotation of keratin genes in the dog and horse genomes (Annotation Release 104 and Annotation Release 102, respectively) and updated annotation and gene nomenclature of several keratin genes. The updates are now available in the NCBI Gene database (https://www.ncbi.nlm.nih.gov/gene).

Fig 1. Comparative map of the keratin type I gene cluster.

Type I keratin genes except KRT18 in the dog, human and horse genomes. Arrows indicate the orientation of the genes. Note that CFA 9 and ECA 11 are represented in reverse orientation with decreasing coordinates from top to bottom. The genes’ nomenclature in the figure corresponds to our updated nomenclature for keratin genes (see Methods). S3 Table details the correspondence of gene symbols to NCBI Gene IDs and RefSeq IDs.

Fig 2. Frameshift deletion in exon 6 of the equine KRT9 gene.

A) Exon 6 alignment of equine KRT9P against the human ortholog KRT9. The yellow block shows the deletion of a single base in the horse exon leading to a frameshift. B) Illumina whole genome sequence and RNA-seq alignment confirms that the equine reference sequence does not contain a sequencing error which supports the claim of deletion. C. Expanded alignment region containing the frameshift deletion.

Fig 3. Comparative map of the keratin type II gene cluster.

Type II keratin genes and KRT18 in the dog (CanFam3.1), human (GRCh38.p2) and horse genomes (EquCab 2.0). Arrows indicate the orientation of the genes. Note that CFA 27 is represented in reverse orientation with decreasing coordinates from top to bottom. The genes’ nomenclature in the figure corresponds to our updated nomenclature for keratin genes (see Methods). S3 Table details the correspondence of gene symbols to NCBI Gene IDs and RefSeq IDs.

Fig 4. Keratin gene structure.

(A) Typical type I keratin gene with eight exons. (B) Typical type II keratin gene with nine exons. The length of conserved exons is given in bp. Untranslated regions are shown as open rectangles.