Long-Term context-dependent genetic adaptation of the viral genetic cloud

Tzipi Braun, Antonio V. Bordería, Cyril Barbezange, Marco Vignuzzi, Yoram Louzoun

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Motivation: RNA viruses generate a cloud of genetic variants within each host. This cloud contains high-frequency genotypes, and many rare variants. The dynamics of these variants is crucial to understand viral evolution and their effect on their host. Results: We use an experimental evolution system to show that the genetic cloud surrounding the Coxsackie virus master sequence slowly, but steadily, evolves over hundreds of generations. This movement is determined by strong context-dependent mutations, where the frequency and type of mutations are affected by neighboring positions, even in silent mutations. This context-dependent mutation pattern serves as a spearhead for the viral population's movement within the adaptive landscape and affects which new dominant variants will emerge. The non-local mutation patterns affect the mutated dinucleotide distribution, and eventually lead to a non-uniform dinucleotide distribution in the main viral sequence. We tested these results on other RNA viruses with similar conclusions. Supplementary information: Supplementary data are available at Bioinformatics online.

Original languageEnglish
Article numberbty891
Pages (from-to)1907-1915
Number of pages9
Issue number11
StatePublished - 1 Jun 2019

Bibliographical note

Funding Information:
This work has received funding from the European Research Council (ERC) under grant agreement No. 242719. T.B. acknowledges funding of the Israel ministry of agriculture NewCastle research grant (11–111–14). The raw data used for this project can be found in the BioProject database under the accession identifier PRJNA420867.

Publisher Copyright:
© 2018 The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.


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