The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans

Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns o...

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Main Authors: Katia Koelle, David A Rasmussen
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2015-09-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/07361
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author Katia Koelle
David A Rasmussen
author_facet Katia Koelle
David A Rasmussen
author_sort Katia Koelle
collection DOAJ
description Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates.
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spelling doaj.art-b33f9e28f6f444f3b94d5007c71dc6e32022-12-22T02:05:06ZengeLife Sciences Publications LtdeLife2050-084X2015-09-01410.7554/eLife.07361The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humansKatia Koelle0David A Rasmussen1Department of Biology, Duke University, Durham, United States; Fogarty International Center, National Institutes of Health, Bethesda, United StatesDepartment of Biology, Duke University, Durham, United States; Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, Basel, SwitzerlandRecent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates.https://elifesciences.org/articles/07361influenza evolutiondeleterious mutationsantigenic evolutionphylodynamics
spellingShingle Katia Koelle
David A Rasmussen
The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans
eLife
influenza evolution
deleterious mutations
antigenic evolution
phylodynamics
title The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans
title_full The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans
title_fullStr The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans
title_full_unstemmed The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans
title_short The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans
title_sort effects of a deleterious mutation load on patterns of influenza a h3n2 s antigenic evolution in humans
topic influenza evolution
deleterious mutations
antigenic evolution
phylodynamics
url https://elifesciences.org/articles/07361
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