tetano
Editor, Senior Moderator
Mol Biol Evol. 2014 Dec 9. pii: msu332. [Epub ahead of print]
Episodic nucleotide substitutions in seasonal influenza virus H3N2 can be explained by stochastic genealogical process without positive selection.
Kim K1, Kim Y2.
Author information
Abstract
Nucleotide substitutions in the HA1 domain of seasonal influenza virus H3N2 occur in temporal clusters, which was interpreted as a result of recurrent selective sweeps underlying antigenic drift. However, classical theory by Watterson suggests that episodic substitutions are mainly due to stochastic genealogy combined with unique genetic structure of influenza virus: high mutation rate over a non-recombining viral segment. This explains why even larger variance in the number of allelic fixations per year is observed in non-antigenic gene segments of H3N2 than in antigenic (HA and NA) segments. Using simulation, we confirm that allelic substitutions at non-recombining segments with high mutation rate become temporally clustered without selection. We conclude that temporal clustering of fixations, as it is primarily caused by inherent randomness in genealogical process at linked sites, cannot be used as an evidence of positive selection in the H3N2 population. This effect of linkage and high mutation rate should be carefully considered in analyzing the genomic patterns of allelic substitutions in asexually reproducing systems in general.
? The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
KEYWORDS:
genealogy; index of dispersion; influenza virus; positive selection; substitution
PMID:
25492497
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25492497
Episodic nucleotide substitutions in seasonal influenza virus H3N2 can be explained by stochastic genealogical process without positive selection.
Kim K1, Kim Y2.
Author information
Abstract
Nucleotide substitutions in the HA1 domain of seasonal influenza virus H3N2 occur in temporal clusters, which was interpreted as a result of recurrent selective sweeps underlying antigenic drift. However, classical theory by Watterson suggests that episodic substitutions are mainly due to stochastic genealogy combined with unique genetic structure of influenza virus: high mutation rate over a non-recombining viral segment. This explains why even larger variance in the number of allelic fixations per year is observed in non-antigenic gene segments of H3N2 than in antigenic (HA and NA) segments. Using simulation, we confirm that allelic substitutions at non-recombining segments with high mutation rate become temporally clustered without selection. We conclude that temporal clustering of fixations, as it is primarily caused by inherent randomness in genealogical process at linked sites, cannot be used as an evidence of positive selection in the H3N2 population. This effect of linkage and high mutation rate should be carefully considered in analyzing the genomic patterns of allelic substitutions in asexually reproducing systems in general.
? The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
KEYWORDS:
genealogy; index of dispersion; influenza virus; positive selection; substitution
PMID:
25492497
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25492497