Graphic Representation of the Evolutionary Relationship between Mouse, Human, and Chimpanzee ABCA1 Proteins

<p>ABCA1 amino acid position 883 genotype is displayed under the species name. An “X” represents the likely point in evolutionary history at which the V883→M883 and M883→I883 mutation events occurred. The M883→I883 mutation likely occurred since the divergence of the last common ancestor between humans and chimpanzees, and the increased activity of the I883 allele suggests that this may have been one of the adaptive changes that occurred during the evolution of modern humans.</p

Comparison of subPSEC Scores for <i>ABCA1</i> cSNPs, Mutations, Recently Described Variants in a Cohort of Individuals with Low HDL Cholesterol from the General Population [14], and a Random Distribution of Low Frequency Alleles

<p><i>ABCA1</i> cSNPs (open circles) have significantly greater subPSEC scores than do mutations (filled squares) (<i>p</i> < 0.0001, Mann-Whitney U test). subPSEC scores for <i>ABCA1</i> variants described in the general population (filled triangles) are significantly different from those of both <i>ABCA1</i> cSNPs and mutations (<i>p</i> < 0.01, Mann-Whitney U test), as well as from the random distribution of <i>ABCA1</i> variants (<i>p</i> < 0.001), indicating that this group of variants consists of both functional and neutral variants.</p

Conservation of ABCA1 Amino Acid Position 1091 in Related Proteins and Functional Effect of Mutation at This Site

<div><p>(A) Multiple sequence alignment adapted from the view of family PTHR19229 available on the PANTHER Web site, showing the ABCA1, ABCA2, ABCA4, and ABCA7 subfamilies. Human ABCA1 position 1091 is highlighted in red; other conserved positions are highlighted in blue.</p><p>(B) Cholesterol efflux was assessed in 293 cells stably transfected with wild-type, M1091T, M1091L, or M1091V ABCA1 alleles. *<i>p</i> < 0.001.</p></div