Parallel evolution between genomic segments of seasonal human influenza viruses reveals RNA-RNA relationships
- University of Pittsburgh, United States
Abstract
The influenza A virus (IAV) genome consists of eight negative-sense viral RNA (vRNA) segments that are selectively assembled into progeny virus particles through RNA-RNA interactions. To explore putative intersegmental RNA-RNA relationships, we quantified similarity between phylogenetic trees comprising each vRNA segment from seasonal human IAV. Intersegmental tree similarity differed between subtype and lineage. While intersegmental relationships were largely conserved over time in H3N2 viruses, they diverged in H1N1 strains isolated before and after the 2009 pandemic. Surprisingly, intersegmental relationships were not driven solely by protein sequence, suggesting that IAV evolution could also be driven by RNA-RNA interactions. Finally, we used confocal microscopy to determine that colocalization of highly coevolved vRNA segments is enriched over other assembly intermediates at the nuclear periphery during productive viral infection. This study illustrates how putative RNA interactions underlying selective assembly of IAV can be interrogated with phylogenetics.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Scripts have been deposited to GitHub as described in the manuscript. Summary tables have been provided for Figures 2-7 and figure supplements.
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Influenza Research Database: An integrated bioinformatics resource for influenza virus researchInfluenza Research Database, doi: 10.1093/nar/gkw857.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (T32 AI049820)
- Jennifer E Jones
Center for Evolutionary Biology and Medicine, University of Pittsburgh
- Jennifer E Jones
National Institute of Allergy and Infectious Diseases (R01 AI139063)
- Seema S Lakdawala
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Jones et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Parallel evolution between genomic segments of seasonal human influenza viruses reveals RNA-RNA relationships
eLife 10:e66525.
https://doi.org/10.7554/eLife.66525
Further reading
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- Evolutionary Biology
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Gene duplication drives evolution by providing raw material for proteins with novel functions. An influential hypothesis by Ohno (1970) posits that gene duplication helps genes tolerate new mutations and thus facilitates the evolution of new phenotypes. Competing hypotheses argue that deleterious mutations will usually inactivate gene duplicates too rapidly for Ohno’s hypothesis to work. We experimentally tested Ohno’s hypothesis by evolving one or exactly two copies of a gene encoding a fluorescent protein in Escherichia coli through several rounds of mutation and selection. We analyzed the genotypic and phenotypic evolutionary dynamics of the evolving populations through high-throughput DNA sequencing, biochemical assays, and engineering of selected variants. In support of Ohno’s hypothesis, populations carrying two gene copies displayed higher mutational robustness than those carrying a single gene copy. Consequently, the double-copy populations experienced relaxed purifying selection, evolved higher phenotypic and genetic diversity, carried more mutations and accumulated combinations of key beneficial mutations earlier. However, their phenotypic evolution was not accelerated, possibly because one gene copy rapidly became inactivated by deleterious mutations. Our work provides an experimental platform to test models of evolution by gene duplication, and it supports alternatives to Ohno’s hypothesis that point to the importance of gene dosage.
