Figure 6. Many previously buffered non-adaptive cis-regulatory changes are unmasked by perturbation of the splicing machinery.

(A) Incidence of Retained Introns (RI) and Skipped Exons (SE) increased after pladienolide B (0.1 μM) treatment (one-sided Wilcoxon signed-rank test). (B) Increase in allelic splicing divergence after pladienolide B treatment. x-axis and y-axis are percent spliced in (PSI) divergence between the two alleles in the DMSO treated sample and the pladienolide B–treated sample, respectively. Events are classified into different groups based on PSI divergence in the two samples. The count of events in each group is indicated by numbers in parentheses. (C) Patterns of PSI divergence after pladienolide B treatment are consistent with those in other F1 tissues. Events were classified into different groups based on allelic splicing divergence after pladienolide B treatment, and the maximal ΔPSI between alleles in F1 tissues are compared for the above groups. (D) Divergent events in F1 tissues are also more likely divergent after pladienolide B treatment and with consistent direction. Events were classified into three groups based on the divergence pattern in F1 tissues, and the ΔPSI (BL6-SPR) values were compared between pladienolide B–treated samples and DMSO-treated samples. Outliers in each group are hidden and the y-axis has been limited to −0.35 to 0.35. One-sided Wilcoxon signed-rank test was used to test difference from zero for median values within each group, whereas one-sided Wilcoxon rank-sum test was used for comparing between groups. Box plot elements: center line, median; box limits, lower and upper quartiles; whiskers, lowest and highest value within 1.5 IQR. n.s., not significant; *P < 0.05; **P < 0.01; ***P < 0.001.