Fig. 3

Tissue-specific regulatory regions have higher evolutionary turnover than tissue-shared regions. a The number of tissue-shared and tissue-specific regulatory regions that are either maintained or recently evolved across all ten species (see Additional file 1: Figure S5). The majority of tissue-shared regulatory regions are maintained across species: 73% of active promoters, 80% of active enhancers, and 75% of primed enhancers. The majority of tissue-specific regions are recently evolved, although 11% of active promoters, 12% of active enhancers and 10% of primed enhancers are maintained. b Evolutionary rates of alignable tissue-shared and tissue-specific regulatory regions estimated by linear regression of activity maintenance between all pairs of species and zero points estimated from interindividual variation (Materials and methods). For tissue-shared regions, the slope of the regression line for active promoters is lower than that of active enhancers or primed enhancers (two-way ANOVA of linear regression: active promoters vs active enhancers p value 0.0063; active promoters vs primed enhancers p value 0.0056). For all tissue-specific regions, the rates of evolution are either indistinguishable or greater than that for tissue-specific primed enhancers (two-way ANOVA of linear regression: active promoters slope vs primed enhancer slope, p value 0.011; active enhancers slope vs primed enhancers slope, p value 0.021). c Evolutionary rates of tissue-specific regulatory regions further stratified by tissue of activity. The slope of the regression line for testis-specific active promoters is significantly higher than for promoters with activity specific to the liver, muscle, or brain (two-way ANOVA of linear regression: testis-specific active promoters vs all other tissue-specific active promoters p value 3 × 10⁻⁸). However, all tissue-specific promoters evolve more rapidly than tissue-shared promoters, regardless of their tissue of activity (two-way ANOVA of linear regression: all tissue-specific active promoters (Fig. 3b) vs tissue-shared active promoters (Fig. 3b) p value 4 × 10⁻⁸)