Rat apolipoprotein A-IV: application of computational methods for studying the structure, function, and evolution of...

There are a great variety of computational methods available to study protein and nucleic acid sequences. The choice of a computer program appropriate to a particular problem and the critical interpretation of the results can lead to specific, and experimentally testable, predictions of a protein's structure and function and may yield insights into its evolution and the location of its gene. We have shown that rat apoA-IV bears a striking structural similarity to human apoA-I (summarized in Fig. 7). Statistical analyses of homologies between apolipoproteins A-I, A-IV, and E demonstrate conclusively that all three sequences diverged from a common ancestral gene. That apoA-IV largely composed of 22 amino acid amphipathic segments with alpha-helical potential suggests that it possesses the structural requirements for LCAT activation. Analysis of the apoB, E receptor-binding domain of human apoE3 has demonstrated that it evolved from an ancestral repeated sequence. Assuming that the genes for these proteins evolved as a result of a series of intra- and intergenic unequal crossovers, it is likely that their genetic loci were at one time linked. The repeated sequences of which these genes are composed have propagated themselves in an expansionary manner. Given this fact, the existence of other genes or pseudogenes based upon this repeated sequence motif is a distinct possibility.