The evolutionarily conserved C-terminal domain of a domesticated transposase-derived protein regulates its DNA integration ability

THAP9 is a transposable element-derived gene that encodes a protein structurally similar to the active Drosophila P-element transposase (DmTNP). Both THAP9 and DmTNP contain a functionally uncharacterized C-terminal domain (CTD) which has a novel fold unique to THAP9 homologs. Phylogenetic analysis revealed that THAP9-CTD homologs are more widespread in the animal kingdom compared to DmTNP-CTD homologs, which are confined to arthropods.

These THAP9-CTD homologs are also more conserved, particularly among mammals and birds, with increasing average length specific to each class. Despite sharing similar secondary structure elements in their CTDs, the evolutionary path and degree of conservation suggest a distinct history for these two CTDs. When the CTDs were removed through truncation mutants, both THAP9 and DmTNP retained the ability to excise and integrate DNA, indicating that the CTDs are not essential for these processes.

However, the removal of the CTD in THAP9 appeared to favor DNA integration, suggesting that the acquisition of this domain during evolution may have contributed to the domestication of THAP9, similar to other transposable element-derived genes like Rag1 and piggybac, which also possess analogous terminal regulatory domains.