Exploring variation in the d(N)/d(S) ratio among sites and lineages using mutational mappings: applications to the influenza virus |
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Authors: | Zhai Weiwei Slatkin Montgomery Nielsen Rasmus |
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Institution: | Department of Integrative Biology, University of California Berkeley, Berkeley, CA 94720-3140, USA. weiweizhai@berkeley.edu |
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Abstract: | We use a likelihood-based method for mapping mutations on a phylogeny in a way that allows for both site-specific and lineage-specific
variation in selection intensity. The method accounts for many of the potential sources of bias encountered in mapping of
mutations on trees while still being computationally efficient. We apply the method to a previously published influenza data
set to investigate hypotheses about changes in selection intensity in influenza strains. Influenza virus is sometimes propagated
in chicken cells for several generations before sequencing, a process that has been hypothesized to induce mutations adapting
the virus to the lab medium. Our analysis suggests that there are approximately twice as many replacement substitutions in
lineages propagated in chicken eggs as in lineages that are not. Previous studies have attempted to predict which viral strains
future epidemics may arise from using inferences regarding positive selection. The assumption is that future epidemics are
more likely to arise from the strains in which positive selection on the so-called “trunk lineages” of the evolutionary tree
is most pervasive. However, we find no difference in the strength of selection in the trunk lineages versus other evolutionary
lineages. Our results suggest that it may be more difficult to use inferences regarding the strength of selection on mutations
to make predictions regarding viral epidemics than previously thought.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Reviewing
Editor: Dr. Willie Swanson |
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Keywords: | Mutational mapping Positive selection Lineage variation Influenza Host-mediated mutations |
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