Evolution of apolipoprotein E: mouse sequence and evidence for an 11-nucleotide ancestral unit.

AUTOR(ES)

Rajavashisth, T B

RESUMO

Apolipoprotein E (apo E) is responsible for the binding of very low density lipoprotein and chylomicron remnants to cellular receptors thereby removing them from circulation. We have isolated and determined the sequence of a cDNA encoding 285 amino acids and the entire 3' untranslated region of 112 nucleotides of mouse apo E. The remaining coding sequence was determined by sequencing mouse liver mRNA. Comparisons with rat and human apo E sequences showed a high degree of conservation although there were regions in each species that were characterized by unique insertions and deletions. Analysis of the sequence homologies within apo E revealed that the entire sequence is made up of repetitive units. The most primitive unit appeared to be an 11-nucleotide repeat within higher order repeats of 22 or 33 nucleotides. The 11-nucleotide unit -TCGGACGAGGC- is read in all three reading frames, and when tandemly repeated, it encodes the highly conserved amino acid sequence Xaa-(Glu/Asp)-(Glu/Asp)-Xaa-Arg-Xaa-Arg-Leu-Gly-Xaa-Xaa. We postulate that apo E and those other apolipoproteins related to it have arisen by duplications and subsequent modifications of this or a closely related 11-nucleotide ancestral sequence.

Documentos Relacionados

• The complete nucleotide sequence of mouse immunoglobin gamma 2a gene and evolution of heavy chain genes: further evidence for intervening sequence-mediated domain transfer.
• Nucleotide sequence through the 18S-28S intergene region of a vertebrate ribosomal transcription unit.
• Relatedness Among Contractile and Membrane Proteins: Evidence for Evolution from Common Ancestral Genes
• Mouse apolipoprotein A-IV gene: nucleotide sequence and induction by a high-lipid diet.
• Nucleotide sequence and structure of the human apolipoprotein E gene.