Mutagenesis scanning uncovers evolutionary constraints on tobacco etch potyvirus membrane-associated 6K2 protein

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• dc.contributor.author González, Rubén
• dc.contributor.author We, Beilei
• dc.contributor.author Li, Xianghua
• dc.contributor.author Martínez, Fernando
• dc.contributor.author Elena, Santiago F.
• dc.date.accessioned 2019-07-19T08:33:32Z
• dc.date.available 2019-07-19T08:33:32Z
• dc.date.issued 2019
• dc.description.abstract RNA virus high mutation rate is a double-edged sword. At the one side, most mutations jeopardize proteins functions; at the other side, mutations are needed to fuel adaptation. The relevant question then is the ratio between beneficial and deleterious mutations. To evaluate this ratio, we created a mutant library of the 6K2 gene of tobacco etch potyvirus that contains every possible single-nucleotide substitution. 6K2 protein anchors the virus replication complex to the network of endoplasmic reticulum membranes. The library was inoculated into the natural host Nicotiana tabacum, allowing competition among all these mutants and selection of those that are potentially viable. We identified 11 nonsynonymous mutations that remain in the viral population at measurable frequencies and evaluated their fitness. Some had fitness values higher than the wild-type and some were deleterious. The effect of these mutations in the structure, transmembrane properties, and function of 6K2 was evaluated in silico. In parallel, the effect of these mutations in infectivity, virus accumulation, symptoms development, and subcellular localization was evaluated in the natural host. The α-helix H1 in the N-terminal part of 6K2 turned out to be under purifying selection, while most observed mutations affect the link between transmembrane α-helices H2 and H3, fusing them into a longer helix and increasing its rigidity. In general, these changes are associated with higher within-host fitness and development of milder or no symptoms. This finding suggests that in nature selection upon 6K2 may result from a tradeoff between within-host accumulation and severity of symptoms.
• dc.description.sponsorship Work in València was supported by the Spanish Agencia Estatal de Investigación - FEDER grant BFU2015-65037-P and Generalitat Valenciana’s grant PROMETEOII/2014/021 to S.F.E. Work in Barcelona was supported by a European Research Council Consolidator grant (616434), the Spanish Ministry of Economy and Competitiveness (grants BFU2011-2606 and SEV-2012-0208), the AXA Research Fund, Agencia de Gestió d’Ajuts Universitaris i Recerca (SGR-831)
• dc.format.mimetype application/pdf
• dc.identifier.citation González R, Wu B, Li X, Martínez F, Elena SF. Mutagenesis scanning uncovers evolutionary constraints on tobacco etch potyvirus membrane-associated 6K2 protein. Genome Biol Evol. 2019 Apr 1; 11(4): 1207-1222. DOI: 10.1093/gbe/evz069
• dc.identifier.doi http://dx.doi.org/10.1093/gbe/evz069
• dc.identifier.issn 1759-6653
• dc.identifier.uri http://hdl.handle.net/10230/42067
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.relation.ispartof Genome Biology and Evolution. 2019 Apr 1;11(4):1207-22
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-65037-P
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/616434
• dc.rights © Rubén González et al. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution License
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Evolució molecular
• dc.subject.other Mutació (Biologia)
• dc.subject.other Potyvirus -- Aspectes genètics
• dc.subject.other Proteïnes virals -- Aspectes genètics
• dc.subject.other Replicació viral
• dc.title Mutagenesis scanning uncovers evolutionary constraints on tobacco etch potyvirus membrane-associated 6K2 protein
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion