Journal of Molecular Evolution

, Volume 86, Issue 8, pp 546–553 | Cite as

Ancestral and Compensatory Mutations that Promote Antiviral Resistance in Influenza N1 Neuraminidase Revealed by a Phylonumerics Approach

  • Elma H. Akand
  • Kevin M. DownardEmail author
Original Article


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.


Antiviral resistance Mutation Influenza Neuraminidase Phylogenetics Mass spectrometry 

Supplementary material

239_2018_9866_MOESM1_ESM.pdf (684 kb)
Supplementary Figure S1 Mutation annotated mass tree for 6406 type A H1N1 human neuraminidase sequences (PDF 683 KB)
239_2018_9866_MOESM2_ESM.docx (15 kb)
Supplementary Table S1 (DOCX 15 KB)
239_2018_9866_MOESM3_ESM.pdf (9 mb)
Supplementary Figure S2 Partial annotated mass tree for node 94 containing S299A mutants of N1 neuraminidase (PDF 9196 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Infectious Disease Responses Laboratory, Prince of Wales Clinical SchoolUniversity of New South WalesSydneyAustralia

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