Theory Article Volume 13, Issue 12 pp 15699—15749

Shifting epigenetic contexts influence regulatory variation and disease risk

Sequence evolution of age-altered regions. (A) Distribution of average per-region sequence conservation (phyloP20ways) in differentially-accessible regions (see color legend). (B) Overlaps of developmental and age-related region sets and human acceleration regions. Overlaps shown relative to set size (per bp of sequence) for background (gray) and target (colored) sets; labels correspond to Supplementary Table 3. (C) Intersections of common human variants (per bp of sequence) for target (colored) and randomized (grey) region sets; labels correspond to results in Supplementary Table 3. (D) Diagram summarizing results of evolutionary sequence analyses. Accessible regions, here diagrammed as an upstream enhancer element (thick blue box), which either gain or lose accessibility over development (left) or ageing (right) exhibit different patterns of evolutionary sequence behavior. Created with BioRender.com. See also Supplementary Figures 7, 8.

Figure 2. Sequence evolution of age-altered regions. (A) Distribution of average per-region sequence conservation (phyloP20ways) in differentially-accessible regions (see color legend). (B) Overlaps of developmental and age-related region sets and human acceleration regions. Overlaps shown relative to set size (per bp of sequence) for background (gray) and target (colored) sets; labels correspond to Supplementary Table 3. (C) Intersections of common human variants (per bp of sequence) for target (colored) and randomized (grey) region sets; labels correspond to results in Supplementary Table 3. (D) Diagram summarizing results of evolutionary sequence analyses. Accessible regions, here diagrammed as an upstream enhancer element (thick blue box), which either gain or lose accessibility over development (left) or ageing (right) exhibit different patterns of evolutionary sequence behavior. Created with BioRender.com. See also Supplementary Figures 7, 8.