biostudies-literatureUnknownArcos SNIAID NIH HHSThe influenza A (IAV) RNA polymerase is an essential driver of IAV evolution. Mutations that the polymerase introduces into viral genome segments during replication are the ultimate source of genetic variation, including within the three subunits of the IAV polymerase (PB2, PB1, and PA). Evolutionary analysis of the IAV polymerase is complicated, because changes in mutation rate, replication speed, and drug resistance involve epistatic interactions among its subunits. In order to study the evolution of the human seasonal H3N2 polymerase since the 1968 pandemic, we identified pairwise evolutionary relationships among ∼7000 H3N2 polymerase sequences using mutual information (MI), which measures the information gained about the identity of one residue when a second residue is known. To accobioRxiv : the preprint server for biology2023.02.16.528850https://www.ebi.ac.uk/biostudies/studies/S-EPMC9949103biostudies-literatureMutual information networks reveal evolutionary relationships within the influenza A virus polymerase.PMC9949103T32 AI007528R01 AI170520Te Velthuis AJWRussell CAHan AXLauring ASArcos SfalseMutual information networks reveal evolutionary relationships within the influenza A virus polymerase.The influenza A (IAV) RNA polymerase is an essential driver of IAV evolution. Mutations that the polymerase introduces into viral genome segments during replication are the ultimate source of genetic variation, including within the three subunits of the IAV polymerase (PB2, PB1, and PA). Evolutionary analysis of the IAV polymerase is complicated, because changes in mutation rate, replication speed, and drug resistance involve epistatic interactions among its subunits. In order to study the evolution of the human seasonal H3N2 polymerase since the 1968 pandemic, we identified pairwise evolutionary relationships among ∼7000 H3N2 polymerase sequences using mutual information (MI), which measures the information gained about the identity of one residue when a second residue is known. To acco2023-01-01T00:00:00Z2023 Feb2026-04-08T12:34:17.742Z2025-04-07T03:18:37.01ZS-EPMC99491033682496210.1101/2023.02.16.528850