Calculated ΔΔG of observed polymorphic amino mutations from the ancestral amino acid residue compared relative to median of all possible mutations at each position.
<p>Free energy changes of polymorphisms in TH2 and TH3 are shown relative to the median change from all 19 substitutions from the predicted ancestral allele determined from <i>Plasmodium sp.</i> phylogeny. Mutations that have higher energy than the median are shown in red, while those with lower energy are shown in blue. Positive values represent increases in free energy and thermodynamic instability while negative values represent decline in free energy and greater stability. Neutral sequence where energetics have no effect would be expected to occur 50/50 above and below the median, while conservation of intramolecular function would be expected to minimize entropy and lead to lower energy states. Intermolecular interactions can lead to selection for less favorable states which are significantly enriched in the observed polymorphisms (17 increased vs 5 decreased, p = 0.00845).</p
