title: Intrasubtype reassortments cause adaptive amino acid replacements in H3N2 influenza genes.
abstract: Reassortments and point mutations are two major contributors to diversity of Influenza A virus; however, the link between these two processes is unclear. It has been suggested that reassortments provoke a temporary increase in the rate of amino acid changes as the viral proteins adapt to new genetic environment, but this phenomenon has not been studied systematically. Here, we use a phylogenetic approach to infer the reassortment events between the 8 segments of influenza A H3N2 virus since its emergence in humans in 1968. We then study the amino acid replacements that occurred in genes encoded in each segment subsequent to reassortments. In five out of eight genes (NA, M1, HA, PB1 and NS1), the reassortment events led to a transient increase in the rate of amino acid replacements on the descendant phylogenetic branches. In NA and HA, the replacements following reassortments were enriched with parallel and/or reversing replacements; in contrast, the replacements at sites responsible for differences between antigenic clusters (in HA) and at sites under positive selection (in NA) were underrepresented among them. Post-reassortment adaptive walks contribute to adaptive evolution in Influenza A: in NA, an average reassortment event causes at least 2.1 amino acid replacements in a reassorted gene, with, on average, 0.43 amino acid replacements per evolving post-reassortment lineage; and at least ~9% of all amino acid replacements are provoked by reassortments.
authors.affiliation: Federal Budget Institution of Science "Central Research Institute for Epidemiology", Moscow, Russia ; Department of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Alexey D
authors.initials: AD
authors.lastname: Neverov
authors.affiliation: Department of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Ksenia V
authors.initials: KV
authors.lastname: Lezhnina
authors.affiliation: Department of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia ; Life Sciences Institute and Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Alexey S
authors.initials: AS
authors.lastname: Kondrashov
authors.affiliation: Department of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia ; Institute for Information Transmission Problems of the Russian Academy of Sciences (Kharkevich Institute), Moscow, Russia.
authors.forename: Georgii A
authors.initials: GA
authors.lastname: Bazykin
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000472:pathogenicity; D007251:Influenza, Human / Q000235:genetics / Q000821:virology; D010802:Phylogeny; D017354:Point Mutation; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D014764:Viral Proteins