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Next, we asked if evolutionary dynamics of promoter and enhancer signatures is correlated to the divergence time between species. For this, we focused on all maintained regulatory regions (The recently evolved and maintained regulomes across species (Fig. (Fig.3a))3a)) between pairs of species and asked how often they align to a regulatory region with another regulatory signature (Evolutionary dynamic regulatory signatures (Fig. (Fig.4b4b and Figure S5)). The comparisons were limited to 1-to-1 aligned regulatory regions.

PWi, j—fraction of maintained active promoters switching regulatory activity between species i and j, i.e., aligned to a regulatory active region, defined as evolutionarily dynamic promoter signatures. See also Eq. 5

PWi → j—number of active promoters in species i aligned to an active or primed enhancer in species j

PMi → j—number of active promoters in species i aligned to any regulatory region in species j; see also Eq. 3

PWj → i—number of active promoters in species j aligned to an active or primed enhancer in species i

PMj → i—number of active promoters in species j aligned to any regulatory region in species i; see also Eq. 3

AAEWi, j—fraction of maintained active enhancers switching regulatory activity between species i and j, i.e., aligned to a regulatory active region, defined as evolutionarily dynamic enhancer signatures. See also Eq. 5

AEWi → j—number of active enhancers in species i aligned to a primed enhancer in species j

AEMi → j—number of active enhancers in species i aligned to any regulatory region in species j; see also Eq. 3

Figure 4c shows the PW, j and AEWi, j between all pairs of species (45 comparisons) for every pair of species at divergence > 0 MYA (45 comparisons) and at divergence = 0 the average intra-species dynamic activity (Intra-species dynamic regulatory signatures (Figs. (Figs.4a4a and S5)). All divergence times between species were taken from Ensembl version 98 [90]. We plotted the resulting graphs in R version 3.6.2 [91] using ggplot2 version 3.1.1 [92] and performed linear regression using the geom_smooth() ggplot2 method

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