Fig. 5.

Substitutions in HARs and HGEs differ in their effects on enhancer activity. (A) Both hSubs and fragments in HGEs (green) and HARs (orange) differ in their level of constraint. (B) hSubs in HGEs have significantly larger effect sizes than hSubs in HARs (Left). However, hSubs in HARs that show evidence of activity in hNSCs based on chromatin signatures do not have significantly larger effects than hSubs in inactive HARs (Middle). hSubs in fragments with evidence of constraint in HGEs show larger effects than hSubs in unconstrained fragments (Right). (C) HARs (orange) and HGEs (green) differ in effect size of their hSubs (shown on the y axis in the scatterplot and in the box plots on the Right) and in evolutionary conservation (measured as the LOD score of phastCons elements overlapping MPRA fragments; shown on the x axis in the scatterplot and in the box plots at the Top of the figure), but these two aspects are uncorrelated.