The hemagglutinin mutation E391K of pandemic 2009 influenza revisited

[tetano]

Mol Phylogenet Evol. 2013 Sep 5. pii: S1055-7903(13)00342-4. doi: 10.1016/j.ympev.2013.08.020. [Epub ahead of print]
The hemagglutinin mutation E391K of pandemic 2009 influenza revisited.
Radomski JP, Płoński P, Zag?rski-Ostoja W.
Source

Interdisciplinary Center for Mathematical and Computational Modeling, Warsaw University, Pawińskiego 5A, Bldg. D, PL-02106 Warsaw, Poland. Electronic address: janr@icm.edu.pl.
Abstract

Phylogenetic analyses based on small to moderately sized sets of sequential data lead to overestimating mutation rates in influenza hemagglutinin (HA) by at least an order of magnitude. Two major underlying reasons are: the incomplete lineage sorting, and a possible absence in the analyzed sequences set some of key missing ancestors. Additionally, during neighbor joining tree reconstruction each mutation is considered equally important, regardless of its nature. Here we have implemented a heuristic method optimizing site dependent factors weighting differently 1st, 2nd, and 3rd codon position mutations, allowing to extricate incorrectly attributed sub-clades. The least squares regression analysis of distribution of frequencies for all mutations observed on a partially disentangled tree for a large set of unique 3243 HA sequences, along all nucleotide positions, was performed for all mutations as well as for non-equivalent amino acid mutations - in both cases demonstrating almost flat gradients, with a very slight downward slope towards the 3'-end positions. The mean mutation rates per sequence per year were 3.8310-4 for the all mutations, and 9.6410-5 for the non-equivalent ones.

Copyright ? 2013 Elsevier Inc. All rights reserved.
KEYWORDS:

Hemagglutinin, Influenza virus, Mutation E391K, Mutation rate, Neighbor joining, Phylogenetic analysis

PMID:
24012880
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/24012880

 

[gsgs]

Re: The hemagglutinin mutation E391K of pandemic 2009 influenza revisited

the abstract doesn't seem to match the headline

mutation rate in influenza is ~2.6*10^-3 per nucleotide position per year
~50% more in human HA 4e-3

 

[gsgs]

Re: The hemagglutinin mutation E391K of pandemic 2009 influenza revisited

3 ****** genomes from 2013, Feb at genbank, from India :
133,144,158 mutations --> 36 mutations per year = 2.76e-3 mutations per year per nucleotide position


1 H3N2 genome from 2013,Jan at genbank, from Singapore :
171 mutations --> 26.6 mutations per year = 2.03e-3 mutations per year per nucleotide -position

the H3N2 genomes from Texas Dec. 2012 have the following differences
to my key-bottleneck-H3N2 viruses, those who are ancesters of
a new strain, that becomes dominant:

differences,differences per year,name,year

1190,26.7,Beijing,1968
1005,24.6,Udorn,1972
0859,25.6,Bangkok,1979
0795,26.8,Hong Kong,1983
0678,28.6,Beijing,1989
0495,31.3,New York,1997
0318,30.3,Fujian,2002
0180,29.0,USA-Index,2007


when you go back in time, the number of differences per year decreases,
since some mutations undo another former mutation and thus reduce
the count by 2 rather than increasing it by one
It may also mutate a bit more in new strains, that are not well
adapted yet

viruses (dots) distant from the green consensus-line are probably
reassortants with other strains (not descending from the
2007-USA-H3N2-index or 2009 panflu resp.) or sequencing errors or
misalignments