The new CTD repeats introduced the potential for ac RPB1 due to the appearance of distal repeats with lysine at position seven.
This was followed by a further increase in the number of lysine-containing repeats in developmentally complex clades like Deuterostomia.
We then performed a genome-wide survey of ac RPB1 occupancy and its influence on gene regulation in mice.
Genes with enrichment for ac RPB1 at their promoters and genes dysregulated when ac RPB1 was disrupted were specifically enriched for functions in growth-factor signaling, cell adhesion, vascular development, and cell-cell interaction.
Eukaryotic RNA polymerases evolved from a single ancestral enzyme into three structurally related RNA polymerase enzymes (I–III) with specialized functions in eukaryotes.
The consensus CTD repeat motif and tandem organization represent the ancestral state of eukaryotic RPB1, but across eukaryotes CTDs show considerable diversity in repeat organization and sequence content.
These differences may reflect lineage-specific CTD functions mediated by protein interactions.
In addition, the two sets of ac RPB1 sensitive genes were enriched for evolutionary origins in early eukaryotes through the ancestor of Euteleostomi (bony vertebrates).
Together, our functional and evolutionary results support a model in which K-containing CTDs were selected for in the early history of animal multicellularity.