<i>Cis</i> regulatory features explain and predict the divergence of RNA editing levels.

<p>(<b>A</b>) The difference in ADAR binding motif scores between sites that are edited (≥10%) in <i>D</i>.<i>mel</i> but not edited (≤1.5%) in other species (green) compared to the difference in sites that are edited (≥10%) in both species (purple). *: <i>p</i> ≤ 0.05, **: <i>p</i> ≤ 0.01, ***: <i>p</i> ≤ 0.001 (one-tailed Mann-Whitney U test) (<b>B</b>) An example of the relationship between structure and editing level changes across species. The editing site is indicated by the purple arrows. (<b>C</b>) The difference in free energy, stem length, and paired bases between sites that are edited (≥10%) in <i>D</i>.<i>mel</i> but not edited (≤1.5%) in other species and control sites that are edited (≥10%) in both species. The numbers of editing sites are indicated above the bars. *: <i>p</i> ≤ 0.05, **: <i>p</i> ≤ 0.01, ***: <i>p</i> ≤ 0.001 (one-tailed Mann-Whitney U test) (<b>D</b>) Relative importance of ADAR motif and dsRNA structural features to predict the establishment of editing (left) and the variation in editing levels (right). In the Presence/Absence editing scenario (left), given that a site was edited (≥10%) in one species, we predicted whether sites were edited (≥10%) or not edited (≤1.5%) in another species. In the Presence/Presence editing scenario (right), given the editing level in one species, we predicted the editing level in another species, requiring that the sites were edited (≥10%) in both species. The <i>D</i>.<i>mel</i>—<i>D</i>.<i>vir</i> comparison is shown. Features with positive and negative relationships with presence of editing (left) or increase of editing level (right) are marked in red and black, respectively. (<b>E</b>) Comparison of predictive accuracy of editing levels of two models (with or without motif and structural features). Given the editing levels in <i>D</i>.<i>mel</i>, editing levels in each of the other species were predicted using the random forests model. Sites with editing level ≥10% in at least one of the paired species were included in the analysis.