Allele-specific nonstationarity in evolution of influenza A virus surface proteinsстатья
Статья опубликована в высокорейтинговом журнале
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 27 ноября 2019 г.
Аннотация:Influenza A virus (IAV) is a major public health problem and a pandemicthreat. Its evolution is largely driven by diversifying positiveselection so that relative fitness of different amino acid variantschanges with time due to changes in herd immunity or genomiccontext, and novel amino acid variants attain fitness advantage.Here, we hypothesize that diversifying selection also has anothermanifestation: the fitness associated with a particular amino acidvariant should decline with time since its origin, as the herd immunityadapts to it. By tracing the evolution of antigenic sites at IAVsurface proteins, we show that an amino acid variant becomes progressivelymore likely to become replaced by another variant withtime since its origin—a phenomenon we call “senescence.” Senescenceis particularly pronounced at experimentally validated antigenicsites, implying that it is largely driven by host immunity. Bycontrast, at internal sites, existing variants become more favorablewith time, probably due to arising contingent mutations at otherepistatically interacting sites. Our findings reveal a previously undescribedfacet of adaptive evolution and suggest approaches for predictionof evolutionary dynamics of pathogens.