Infectious Disease Responses Laboratory, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia.
J Mol Evol. 2018 Oct;86(8):546-553. doi: 10.1007/s00239-018-9866-4. Epub 2018 Oct 9.
Implementation of a new phylonumerics approach to construct a mass tree representing over 6000 H1N1 human influenza strains has enabled ancestral and compensatory descendant mutations to be identified in N1 neuraminidase that promote antiviral resistance and restore viral fitness. Adjacent to the H275Y resistance mutation site, mutations S299A and S247N, respectively, lead the evolution of oseltamivir-resistant strains and restore viral fitness to those strains thereafter. Importantly the mass tree phylonumerics approach can identify such mutations globally, without any positional bias, so that functionally linked or compensatory mutations remote in the sequence or structure of the protein can be identified and interrogated. This is achieved using mass map datasets commonly employed for protein identification in proteomics applications, thus avoiding the need for either gene or protein sequences that are central to other phylogenetic methods.
实施一种新的系统发育数值方法来构建一个代表超过 6000 株 H1N1 人流感病毒株的质量树，使得能够鉴定 N1 神经氨酸酶中促进抗病毒耐药性和恢复病毒适应性的祖先和补偿性后代突变。在 H275Y 耐药性突变位点附近，突变 S299A 和 S247N 分别导致奥司他韦耐药株的进化，并使这些株系恢复病毒适应性。重要的是，质量树系统发育数值方法可以在全球范围内识别此类突变，而不会有任何位置偏见，从而可以识别和研究序列或结构上远程的功能相关或补偿性突变。这是通过使用通常用于蛋白质组学应用中蛋白质鉴定的质量图谱数据集来实现的，从而避免了对其他系统发育方法至关重要的基因或蛋白质序列的需要。
