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, Georgii A. Bazykin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 unde-scribed facet of adaptive evolution and suggest approaches for prediction of evolutionary dynamics of pathogens.

Original languageEnglish (US)
Pages (from-to)21104-21112
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number42
StatePublished - Oct 15 2019


  • Influenza
  • Nonstationary evolution
  • Selection

ASJC Scopus subject areas

  • General


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