Isolation and characterization of a processed gene for human ceruloplasmin.
A processed pseudogene for human ceruloplasmin has been isolated that contains DNA corresponding to the functional gene sequence encoding the carboxy-terminal 563 amino acid residues and the 3' untranslated region. The pseudogene appears to have arisen from a processed RNA species, since intervening sequences coincident with those of the functional gene have been removed, with the exception of a short segment of intronic sequence which denotes the 5' boundary of the pseudogene. The nucleotide sequence of the pseudogene is highly homologous (97% sequence identity) with that of the wild-type gene, suggesting that pseudogene formation was a relatively recent evolutionary event. In addition to single base substitutions, there is a large 213 base pair (bp) deletion in the pseudogene sequence which corresponds to the location of an intron-exon junction in the functional gene. A 4 bp duplication that occurs at amino acid residue 683 of the wild-type coding sequence results in a frameshift mutation and introduces a premature translational termination codon at this point. This is concordant with the inability to detect a human liver transcript corresponding to the pseudogene by nuclease S1 mapping analysis. The 3' end of the pseudogene is characterized by a 62 bp segment composed mainly of repeated TC dinucleotides. On the basis of genomic Southern blot analysis performed under high-stringency conditions, the pseudogene that we have identified seems to comprise the only sequence in the human genome that is closely related to the wild-type gene. Using somatic cell hybridization, we have mapped the pseudogene to human chromosome 8.(ABSTRACT TRUNCATED AT 250 WORDS)
Koschinsky
M L
ML
Department of Biochemistry, University of British Columbia, Vancouver, Canada.
Chow
B K
BK
Schwartz
J
J
Hamerton
J L
JL
MacGillivray
R T
RT
D001483:Base Sequence; D002570:Ceruloplasmin / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification*; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011544:Pseudogenes; D014158:Transcription, Genetic
D004247:DNA; D002570:Ceruloplasmin