tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2019 Oct 2. pii: 201904246. doi: 10.1073/pnas.1904246116. [Epub ahead of print] [h=1]Allele-specific nonstationarity in evolution of influenza A virus surface proteins.[/h]
Popova AV[SUP]1[/SUP], Safina KR[SUP]2,[/SUP][SUP]3[/SUP], Ptushenko VV[SUP]4,[/SUP][SUP]5[/SUP], Stolyarova AV[SUP]2[/SUP], Favorov AV[SUP]6,[/SUP][SUP]7[/SUP], Neverov AD[SUP]1[/SUP], Bazykin GA[SUP]8,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h] 1 Department of Molecular Diagnostics, Central Research Institute for Epidemiology, Moscow, 111123 Russia. 2 Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, 143028 Russia. 3 Institute for Information Transmission Problems (Kharkevich Institute), Russian Academy of Sciences, Moscow, 127051 Russia. 4 A. N. Belozersky Institute of Physical-Chemical Biology, M. V. Lomonosov Moscow State University, Moscow, 119992 Russia. 5 Department of Photochemistry and Photobiology, N. M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, Moscow, 119334 Russia. 6 Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21205. 7 Laboratory of System Biology and Computational Genetics, Vavilov Institute of General Genetics, Moscow, 119991 Russia. 8 Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, 143028 Russia; g.bazykin@skoltech.ru.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] influenza; nonstationary evolution; selection
PMID: 31578251 DOI: 10.1073/pnas.1904246116
Popova AV[SUP]1[/SUP], Safina KR[SUP]2,[/SUP][SUP]3[/SUP], Ptushenko VV[SUP]4,[/SUP][SUP]5[/SUP], Stolyarova AV[SUP]2[/SUP], Favorov AV[SUP]6,[/SUP][SUP]7[/SUP], Neverov AD[SUP]1[/SUP], Bazykin GA[SUP]8,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h] 1 Department of Molecular Diagnostics, Central Research Institute for Epidemiology, Moscow, 111123 Russia. 2 Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, 143028 Russia. 3 Institute for Information Transmission Problems (Kharkevich Institute), Russian Academy of Sciences, Moscow, 127051 Russia. 4 A. N. Belozersky Institute of Physical-Chemical Biology, M. V. Lomonosov Moscow State University, Moscow, 119992 Russia. 5 Department of Photochemistry and Photobiology, N. M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, Moscow, 119334 Russia. 6 Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21205. 7 Laboratory of System Biology and Computational Genetics, Vavilov Institute of General Genetics, Moscow, 119991 Russia. 8 Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, 143028 Russia; g.bazykin@skoltech.ru.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] influenza; nonstationary evolution; selection
PMID: 31578251 DOI: 10.1073/pnas.1904246116