Evolutionary dynamics of the N1 neuraminidases of the main lineages of influenza A viruses.
ABSTRACT Influenza A virus infects a wide range of hosts including birds, humans, pigs, horses, and other mammals. Because hosts differ in immune system structure and demography, it is therefore expected that host populations leave different imprints on the viral genome. In this study, we investigated the evolutionary trajectory of the main lineages of N1 type neuraminidase (NA) gene sequences of influenza A viruses by estimating their evolutionary rates and the selection pressures exerted upon them. We also estimated the time of emergence of these lineages. The Eurasian (avian-like) and North American (classical) swine lineages, the human (seasonal) and avian H5N1 lineages, and a long persisting avian lineage were studied and compared. Nucleotide substitution rates ranged from 1.9x10(-3) to 4.3x10(-3) substitutions per site per year, with the H5N1 lineage estimated to have the greatest rate. The evolutionary rates of the H1N1 human lineage appeared to be slightly greater after it re-emerged in 1977 than before it disappeared in the 1950s. Comparing across the lineages, substitution rates appeared to correlate with the number of positively selected sites and with the degree of asymmetry of the phylogenetic trees. Some lineages had strongly asymmetric trees, implying repeated genotype replacement and narrow genetic diversity. Positively selected sites were identified in all lineages, with the H5N1 lineage having the largest number. A great number of isolates of the H5N1 lineage were sequenced in a short time period and the phylogeny of the lineage was more symmetric. We speculate that the rate and selection estimations made for this lineage could have been influenced by sampling and may not represent the long-term trends.
Article: Evolutionary history and phylodynamics of influenza A and B neuraminidase (NA) genes inferred from large-scale sequence analyses.[show abstract] [hide abstract]
ABSTRACT: Influenza neuraminidase (NA) is an important surface glycoprotein and plays a vital role in viral replication and drug development. The NA is found in influenza A and B viruses, with nine subtypes classified in influenza A. The complete knowledge of influenza NA evolutionary history and phylodynamics, although critical for the prevention and control of influenza epidemics and pandemics, remains lacking. Evolutionary and phylogenetic analyses of influenza NA sequences using Maximum Likelihood and Bayesian MCMC methods demonstrated that the divergence of influenza viruses into types A and B occurred earlier than the divergence of influenza A NA subtypes. Twenty-three lineages were identified within influenza A, two lineages were classified within influenza B, and most lineages were specific to host, subtype or geographical location. Interestingly, evolutionary rates vary not only among lineages but also among branches within lineages. The estimated tMRCAs of influenza lineages suggest that the viruses of different lineages emerge several months or even years before their initial detection. The d(N)/d(S) ratios ranged from 0.062 to 0.313 for influenza A lineages, and 0.257 to 0.259 for influenza B lineages. Structural analyses revealed that all positively selected sites are at the surface of the NA protein, with a number of sites found to be important for host antibody and drug binding. The divergence into influenza type A and B from a putative ancestral NA was followed by the divergence of type A into nine NA subtypes, of which 23 lineages subsequently diverged. This study provides a better understanding of influenza NA lineages and their evolutionary dynamics, which may facilitate early detection of newly emerging influenza viruses and thus improve influenza surveillance.PLoS ONE 01/2012; 7(7):e38665. · 4.09 Impact Factor