Figure 6.

Compensatory promoter turnover and positive selection. (A) Human, mouse, and horse alignments at the PDE4C locus. Four promoters are shown, which are conserved (promoters 1 and 3), human-deleted (promoter 2), or mouse-deleted (promoter 4). Gene models supported by the CAGE promoters are shown in the blue boxes, where solid boxes represent coding exons and empty boxes noncoding exons. The histograms in red describe the log₂-transformed expression level of the annotated promoters. Orthologous sequence identified between species is highlighted by the green boxes between these sequences. (B) Frequencies of 1:1 orthologous genes in human and mouse categorized by the type of promoter sequence turnover events. The blue circles represent genes with a greater proportion of promoter births than deaths, while the purple circles similarly represent genes with a greater proportion of promoter deaths. Genes with an equal number of promoter births and deaths are shown in the yellow circles. All genes are shown in the outer circles, while the numbers in the inner circles shows those with evidence for compensatory promoter turnovers. Genes with only expression turnover at their promoters are shown in the orange segment, while the remainder of the green circle indicates the number of genes with a conserved promoter architecture (C,D). Enrichments of human orthologous genes with different turnover events and expression profiles relative to genes with a conserved promoter architecture. χ² test, (*) P < 0.05, (**) P < 0.01, (***) P < 0.001. (E) Enrichments of orthologous genes with coding sequence positive selection. Genes are classified by the possible different evolutionary outcomes of their associated promoters relative to genes with a conserved promoter architecture. χ² test, (*) P < 0.05, (**) P < 0.01, (***) P < 0.001.