Markin Alexey, Macken Catherine A, Baker Amy L, Anderson Tavis K
Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, Iowa 50010, USA.
Bioinformatics Institute, University of Auckland, Auckland, New Zealand.
Mol Biol Evol. 2025 Jul 30;42(8). doi: 10.1093/molbev/msaf133.
Reassortment among influenza A viruses (IAV) facilitates evolution and has been associated with interspecies transmission and pandemics. We introduce a novel tool called TreeSort that accurately identifies recent and ancestral reassortment events on datasets with thousands of IAV whole genomes. TreeSort uses the phylogeny of a selected IAV segment as a reference and finds the branches on the phylogeny where reassortment has occurred with high probability. The tool reports the particular gene segments that were involved in reassortment and how different they are from prior gene pairings. Using TreeSort, we studied reassortment patterns of different IAV subtypes isolated in avian, swine, and human hosts. Avian IAV demonstrated more reassortment than human and swine IAV, with the avian H7 subtype displaying the most frequent reassortment. Reassortment in the swine and human H3 subtypes was more frequent than in the swine and human H1 subtypes, respectively. The highly pathogenic avian influenza H5N1 clade 2.3.4.4b had elevated reassortment rates in the 2020 to 2023 period; however, the surface protein-encoding genes (HA, NA, and MP) co-evolved together with almost no reassortment among these genes. We observed similar co-evolutionary patterns with very low rates of reassortment among the surface proteins for the human H1 and H3 lineages, suggesting that strong co-evolution and preferential pairings among surface proteins are a consequence of high viral fitness. Our algorithm enables real-time tracking of IAV reassortment within and across different hosts and can identify novel viruses for pandemic risk assessment. TreeSort is available at https://github.com/flu-crew/TreeSort.
甲型流感病毒（IAV）之间的基因重配促进了病毒进化，并与跨物种传播和大流行有关。我们引入了一种名为TreeSort的新工具，它可以准确识别包含数千个IAV全基因组的数据集上的近期和祖先基因重配事件。TreeSort以选定的IAV片段的系统发育为参考，在系统发育树上找到重配发生概率很高的分支。该工具报告参与重配的特定基因片段以及它们与先前基因配对的差异程度。使用TreeSort，我们研究了在禽类、猪和人类宿主中分离出的不同IAV亚型的重配模式。禽IAV的重配比人类和猪IAV更多，其中禽H7亚型的重配最为频繁。猪和人类H3亚型中的重配比猪和人类H1亚型中的重配分别更为频繁。高致病性禽流感H5N1进化枝2.3.4.4b在2020年至2023年期间重配率升高；然而，编码表面蛋白的基因（HA、NA和MP）共同进化，这些基因之间几乎没有重配。我们在人类H1和H3谱系的表面蛋白中观察到了类似的共同进化模式，重配率非常低，这表明表面蛋白之间强烈的共同进化和优先配对是高病毒适应性的结果。我们的算法能够实时跟踪不同宿主内部和之间的IAV重配，并可以识别用于大流行风险评估的新型病毒。TreeSort可在https://github.com/flu-crew/TreeSort上获取。
