Hugo Castelan-Sanchez, Art Poon. [preprint]Phylogenetic discordance cannot identify genomic reassortment events: a case study with the avian influenza virus H5Nx. https://doi.org/10.1101/2025.02.24.639875
Recombination plays a central role in the evolution of the RNA virus genome, as it allows the exchange of genetic material between different viral lineages. Reassortment is a form of recombination specific to viruses with segmented genomes that involves the exchange of entire segments between lineages. This process has played a significant role in the adaptation and spread of influenza viruses, where novel combinations of genomic segments are produced from divergent lineages (i.e., antigenic shift). In this study, we investigated reassortment events in a representative sample of n = 11, 765 complete genomes of H5Nx influenza A viruses from avian hosts. Using tanglegrams and subtree-prune-regraft (SPR) methods to quantify discordance between segment trees, we found evidence of widespread reassortment among these genomes that is consistent with previous studies. However, we obtained the comparable numbers of reassortment events when applying the same methods to sequence data simulated in the complete absence of any reassortment. This outcome indicates a high false positive rate in identifying reassortment events due to uncertainty in phylogenetic reconstruction. There was also no significant difference between SPR events inferred from real data versus simulated false positives with respect to subtree size, or the distance between prune and regraft points in the reference tree. Although there is no doubt that reassorment has played a significant role in the origin of new pandemic strains of influenza viruses, these results imply that previous reports of extensive reassortment in the avian influenza virus literature should be interpreted with caution.
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