Domain innovation and deeply conserved intrinsic disorders in eukaryotic argonaute

Argonaute (Ago) proteins are distributed across all domains of life and play central roles in the defence against mobile genetic elements. We performed extensive searches of Ago proteins across eukaryotes. We revealed wide variability in the genomic content of Agos and unprecedented diversity of domain occurrence, with some domain architectures reminiscent of those of prokaryotic defence systems. We also show that most Agos feature intrinsically disordered protein regions (IDRs) at their termini. In this context, we report unusually deep conservation of the primary sequence and ensemble features of C-terminal IDRs across large evolutionary distances. We thus suggest that the C-terminal IDRs of Ago proteins evolved under stabilizing selection to maintain a shared function. Altogether, this study provides insight into the evolution and diversity of Ago proteins in eukaryotes.