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

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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