Evolutionary insights reveal a new role of peptidyl arginine deiminase 2 in transcription regulation

Evolutionary insights reveal a new role of peptidyl arginine deiminase 2 in transcription regulationA systematic evolutionary analysis identified positively selected residues in the non-catalytic domain of PADI2. We established a link between the positive evolution of key residues in the PADI2 and their role in transcription. Specifically, we identified the structurally exposed loop encompassing the positively selected L162 in the PADI2 middle domain and its role in transcription and cellular proliferation. This loop contributes to the PADI2 interaction with the P-TEFb complex and cellular proliferation. Our results showcase the use of combining evolutionary and experimental approaches to dissect the dynamic of evolutionary processes. Hela cells expressing the wild-type (WT) and mutant (L162A/W161A/T159A) peptidyl arginine deiminase 2 (PADI2) were used for single cell sequecing.