text: The natural selection power for dephosphorylation is less understood. A recent study has found that IRF9, which is from the interferon-regulatory factors family (IRFs), a critical family for anti-viral immune response, could be influenced by natural selection during Human species evolution. The positive selection has been found on the amino acid site Val129 (NP_006075.3:p.Ser129Val) of human IRF9. The ancestral state (Ser129) is conserved among mammals, while the novel state (Val129) was fixed before the "out-of-Africa" event ~ 500,000 years ago. This young amino acid (Val129) may serve as a dephosphorylation site of IRF9. The dephosphorylation may affect the immune activity of IRF9.