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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
Published on: June 16, 2011
Contingent neutrality in competing viral populations
J Quer1, C L Hershey, E Domingo
1Department of Biology and Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093-0116, USA.
Journal of Virology
|July 20, 2001
Summary
Environmental stress accelerates wild-type vesicular stomatitis virus dominance over a genetically marked (MARM-C) population. This suggests MARM-C
Area of Science:
- Virology
- Evolutionary Biology
- Genetics
Background:
- Vesicular stomatitis virus (VSV) populations exhibit complex fitness dynamics.
- A genetically marked VSV (MARM-C) population initially competes equally with wild-type (wt) virus.
- Prolonged competition typically results in wt virus dominance over MARM-C.
Purpose of the Study:
- To investigate the contingent nature of MARM-C's neutral fitness.
- To determine how environmental perturbations affect MARM-C vs. wt virus competition.
- To elucidate the genomic basis for MARM-C's fitness characteristics.
Main Methods:
- Competition assays between MARM-C and wt VSV in BHK-21 cells.
- Introduction of environmental perturbations: defective interfering particles, 5-fluorouracil (5-FU), and elevated temperature (40.5°C).
- Genomic consensus sequencing of the MARM-C population.
Main Results:
- Environmental perturbations significantly accelerated wt VSV dominance over MARM-C.
- MARM-C possesses six identified mutations in its consensus genome.
- Independent passage in 5-FU did not alter MARM-C or wt fitness or subsequent competition ability.
Conclusions:
- MARM-C's neutral fitness is contingent on environmental conditions.
- Environmental stress hinders MARM-C's ability to generate compensatory mutations compared to wt VSV.
- A model of contingent neutrality is proposed, where MARM-C occupies a neutral fitness landscape vulnerable to stress.
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