Structure and evolution of apolipoprotein genes
Abstract
The aim of this dissertation is to study the structure and evolution of apolipoprotein genes by a combination of experimental and statistical approaches. Apolipoproteins are biologically and clinically important because they are the protein components of plasma lipoproteins, which are the major carriers of various lipids in human blood. The results obtained are as follows: (1) The cDNAs for three dog apolipoproteins (apoA-I, apoC-I and apoE) are cloned and sequenced. (2) The mature peptide regions of the genes for apoA-I, A-II, A-IV, C-I, C-II, C-III and E are almost completely made up of tandem repeats of 11 codons. The part of the mature peptide region encoded by exon 3 contains a common block of 33 codons comprising three repeats of 11 codons, whereas the part encoded by exon 4 contains a much more variable number of internal repeats of 11 codons. These genes have apparently evolved from a primordial gene through multiple partial (internal) and complete gene duplications. (3) ApoA-II, C-I, C-II and C-III have evolved rapidly and apoA-I, A-IV and E also have evolved at high rates but some regions are better conserved than the others. Structural requirements in domains for LPL activation (apoC-II) and receptor binding (apoE) are stringent whereas those for LCAT activation and lipid binding domains are not. (4) Both synonymous and nonsynonymous rates of nucleotide substitution are much higher in the rat lineage than in the human and dog lineages. (5) An evolutionary tree for the apolipoprotein genes is proposed and rough estimates of the divergence times are obtained.
Subject Area
Genetics
Recommended Citation
Luo, Chi-Cheng, "Structure and evolution of apolipoprotein genes" (1987). Texas Medical Center Dissertations (via ProQuest). AAI8804370.
https://digitalcommons.library.tmc.edu/dissertations/AAI8804370