Figure 4

Relative activities of endogenous ligands on five different PRXamide receptors (a), a plot showing relatedness of the sequence diversities and ligand specificities of PRXamide receptors (b) and a simplified diagram showing the asymmetric cross activities of ligands on target receptors (c).
(a) Values in the matrix are for log (EC50) normalized by the lowest EC50 for each receptor. The evolutionary tree based on GPCR amino acid sequence (top) is different from the tree inferred based on the ligand specificity (bottom). Color codes for each cell are low activity (green) to high activity (red). See Materials and Methods for further details. (b) Pairwise distances between receptors. Comparative distances between the distances based on ligand specificity (X-axis) and based on sequence similarity (Y-axis) for each pair of receptors are plotted. Error bars are for the standard error generated in 1000 bootstrapping in the sequence distances. The distance was normalized by the largest distance as 1. Regressed line is with 95% confidence interval (shaded area). Blue arrow implies directions of evolutionary forces for positive or negative pleiotropism. (c) Values in Figure 4a are used to depict a simplified view of asymmetry in pleiotropism. The line color indicates degree of activity; darker lines depict stronger activity.