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Selection on non-antigenic gene segments of seasonal influenza A virus and its impact on adaptive evolution

View ORCID ProfileJayna Raghwani, Robin Thompson, View ORCID ProfileKatia Koelle
doi: https://doi.org/10.1101/166082
Jayna Raghwani
1Department of Zoology, University of Oxford, Oxford, United Kingdom
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  • For correspondence: jayna.raghwani@zoo.ox.ac.uk
Robin Thompson
1Department of Zoology, University of Oxford, Oxford, United Kingdom
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Katia Koelle
2Department of Biology, Duke University, Durham, United States
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ABSTRACT

Most studies on seasonal influenza A/H3N2 virus adaptation have focused on the main antigenic gene, haemagglutinin. However, there is increasing evidence that the genome-wide genetic background of novel antigenic variants can influence these variants’ emergence probabilities and impact their patterns of dominance in the population. This suggests that non-antigenic genes may be important in shaping the viral evolutionary dynamics. To better understand the role of selection on non-antigenic genes in the adaptive evolution of seasonal influenza viruses, we here develop a simple population genetic model that considers a virus with one antigenic and one non-antigenic gene segment. By simulating this model under different regimes of selection and reassortment, we find that the empirical patterns of lineage turnover for the antigenic and non-antigenic gene segments are best captured when there is both limited viral coinfection and selection operating on both gene segments. In contrast, under a scenario of only neutral evolution in the non-antigenic gene segment, we see persistence of multiple lineages for long periods of time in that segment, which is not compatible with the observed molecular evolutionary patterns. Further, we find that reassortment, occurring in coinfected individuals, can increase the speed of viral adaptive evolution by primarily reducing selective interference and genetic linkage effects mediated by the non-antigenic gene segment. Together, these findings suggest that, for influenza, with 6 internal or non-antigenic gene segments, the evolutionary dynamics of novel antigenic variants are likely to be influenced by the genome-wide genetic background as a result of linked selection among both beneficial and deleterious mutations.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 21, 2017.
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Selection on non-antigenic gene segments of seasonal influenza A virus and its impact on adaptive evolution
Jayna Raghwani, Robin Thompson, Katia Koelle
bioRxiv 166082; doi: https://doi.org/10.1101/166082
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Selection on non-antigenic gene segments of seasonal influenza A virus and its impact on adaptive evolution
Jayna Raghwani, Robin Thompson, Katia Koelle
bioRxiv 166082; doi: https://doi.org/10.1101/166082

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