Two copies of the human apolipoprotein C-I gene are linked closely to the apolipoprotein E gene.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Lauer, S J; Walker, D; Elshourbagy, N A; Reardon, C A; Levy-Wilson, B; Taylor, J M
Year of Publication: 1988
Journal: J Biol Chem
Volume: 263
Issue: 15
Pagination: 7277-86
Date Published: 1988 May 25
Publication Language: eng
ISSN: 0021-9258
Keywords: Amino Acid Sequence, Apolipoprotein C-I, Apolipoproteins, Apolipoproteins C, Apolipoproteins E, Base Sequence, Biological Evolution, Cloning, Molecular, DNA Restriction Enzymes, Exons, Genes, Genetic Linkage, Humans, Liver, Macrophages, Male, Molecular Sequence Data, Organ Specificity
Abstract:

The gene for human apolipoprotein (apo) C-I was selected from human genomic cosmid and lambda libraries. Restriction endonuclease analysis showed that the gene for apoC-I is located 5.5 kilobases downstream of the gene for apoE. A copy of the apoC-I gene, apoC-I', is located 7.5 kilobases downstream of the apoC-I gene. Both genes contain four exons and three introns; the apoC-I gene is 4653 base pairs long, the apoC-I' gene 4387 base pairs. In each gene, the first intron is located 20 nucleotides upstream from the translation start signal; the second intron, within the codon of Gly-7 of the signal peptide region; and the third intron, within the codon for Arg39 of the mature plasma protein coding region. The upstream apoC-I gene encodes the known apoC-I plasma protein and differs from the downstream apoC-I' gene in about 9% of the exon nucleotide positions. The most important difference between the exons results in a change in the codon for Gln-2 of the signal peptide region, which introduces a translation stop signal in the downstream gene. Major sequence differences are found in the second and third introns of the apoC-I and apoC-I' genes, which contain 9 and 7.5 copies, respectively, of Alu family sequences. The apoC-I gene is expressed primarily in the liver, and it is activated when monocytes differentiate into macrophages. In contrast, no mRNA product of the apoC-I' gene can be detected in any tissue, suggesting that it may be a pseudogene. The similar structures and the proximity of the apoE and apoC-I genes suggest that they are derived from a common ancestor. Furthermore, they may be considered to be constituents of a family of seven apolipoprotein genes (apoE, -C-I, -C-II, -C-III, -A-I, -A-II, and -A-IV) that have a common evolutionary origin.

Alternate Journal: J. Biol. Chem.
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