Complete Genomic Sequence and Analysis of the Prion Protein Gene Region from Three Mammalian Species

• DOI: 10.1101/gr.8.10.1022
• Publication Date: 2017-05-03T00:28:30Z
• Authors: Inyoul Y. Lee; David Westaway; Arian F.A. Smit; Kai Wang; Jason Seto; Lei Chen; Chetana Acharya; Mike Ankener; Dale Baskin; Carol Cooper; Hong Yao; Stanley B. Prusiner; Leroy E. Hood
• Keywords: Viral Structural Proteins; 0301 basic medicine; Base Composition; 0303 health sciences; Sheep; Base Sequence; Genes, Viral; Prions; Molecular Sequence Data; Mice, Inbred Strains; Sequence Analysis, DNA; Mice; 03 medical and health sciences; Long Interspersed Nucleotide Elements; Retroviridae; Animals; Humans; CpG Islands; Amino Acid Sequence; Sequence Alignment; Short Interspersed Nucleotide Elements

The prion protein (PrP), first identified in scrapie-infected rodents, is encoded by a single exon of a single-copy chromosomal gene. In addition to the protein-coding exon, PrP genes in mammals contain one or two 5′-noncoding exons. To learn more about the genomic organization of regions surrounding the PrP exons, we sequenced 105 bp of DNA from clones containing human, sheep, and mouse PrP genes isolated in cosmids or λ phage. Our findings are as follows: (1) Although the human PrP transcript does not include the untranslated exon 2 found in its mouse and sheep counterparts, the large intron of the human PrP gene contains an exon 2-like sequence flanked by consensus splice acceptor and donor sites. (2) The mouse Prnpa but not thePrnpb allele found in 44 inbred lines contains a 6593 nucleotide retroviral genome inserted into the anticoding strand of intron 2. This intracisternal A-particle element is flanked by duplications of an AAGGCT nucleotide motif. (3) We found that thePrP gene regions contain from 40% to 57% genome-wide repetitive elements that independently increased the size of the locus in all three species by numerous mutations. The unusually long sheepPrP 3′-untranslated region contains a “fossil” 1.2-kb mariner transposable element. (4) We identified sequences in noncoding DNA that are conserved between the three species and may represent biologically functional sites.[The nucleotide sequence data reported in this paper have been submitted to the GenBank sequence database and have been assigned the accession numbers U29185(human), U29186 (mouse), and U67922 (sheep).]