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PNAS: Allele-specific nonstationarity in evolution of influenza A virus surface proteins

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  • PNAS: Allele-specific nonstationarity in evolution of influenza A virus surface proteins

    Allele-specific nonstationarity in evolution of influenza A virus surface proteins

    Anfisa V. Popova, Ksenia R. Safina, Vasily V. Ptushenko, Anastasia V. Stolyarova, Alexander V. Favorov, Alexey D. Neverov, and Georgii A. Bazykin
    PNAS first published October 2, 2019 https://doi.org/10.1073/pnas.1904246116
    • Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved September 11, 2019 (received for review March 15, 2019)









    Significance

    Control of rapidly evolving pathogens requires prediction of evolution. One obstacle to such predictions is the ever-changing environment, which determines strain fitness. Here, we show that fitness conferred by an amino acid variant at surface proteins of influenza A virus changes systematically with time since this variant appeared. The direction of this change depends on its functional role. At antigenic regions, variants become less fit with time. Conversely, variants at internal regions become more fit with time. This dynamic can be explained by a simple model: while the fitness of amino acids deeply embedded in the protein increases due to substitutions elsewhere, that of amino acids exposed to the immune system drops as herd immunity adapts to them.

    Abstract

    Influenza A virus (IAV) is a major public health problem and a pandemic threat. Its evolution is largely driven by diversifying positive selection so that relative fitness of different amino acid variants changes with time due to changes in herd immunity or genomic context, and novel amino acid variants attain fitness advantage. Here, we hypothesize that diversifying selection also has another manifestation: the fitness associated with a particular amino acid variant should decline with time since its origin, as the herd immunity adapts to it. By tracing the evolution of antigenic sites at IAV surface proteins, we show that an amino acid variant becomes progressively more likely to become replaced by another variant with time since its origin—a phenomenon we call “senescence.” Senescence is particularly pronounced at experimentally validated antigenic sites, implying that it is largely driven by host immunity. By contrast, at internal sites, existing variants become more favorable with time, probably due to arising contingent mutations at other epistatically interacting sites. Our findings reveal a previously undescribed facet of adaptive evolution and suggest approaches for prediction of evolutionary dynamics of pathogens.

    https://www.pnas.org/content/early/2.../01/1904246116













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