showing 5 related works from this author
Selection for Robustness in Mutagenized RNA Viruses
2007
Mutational robustness is defined as the constancy of a phenotype in the face of deleterious mutations. Whether robustness can be directly favored by natural selection remains controversial. Theory and in silico experiments predict that, at high mutation rates, slow-replicating genotypes can potentially outcompete faster counterparts if they benefit from a higher robustness. Here, we experimentally validate this hypothesis, dubbed the ‘‘survival of the flattest,’’ using two populations of the vesicular stomatitis RNA virus. Characterization of fitness distributions and genetic variability indicated that one population showed a higher replication rate, whereas the other was more robust to mut…
The cost of replication fidelity in an RNA virus
2005
It is often argued that high mutation rates are advantageous for RNA viruses, because they confer elevated rates of adaptation. However, there is no direct evidence showing a positive correlation between mutation and adaptation rates among RNA viruses. Moreover, theoretical work does not argue in favor of this prediction. We used a series of vesicular stomatitis virus clones harboring single amino acid substitutions in the RNA polymerase to demonstrate that changes inducing enhanced fidelity paid a fitness cost, but that there was no positive correlation between mutation an adaptation rates. We demonstrate that the observed mutation rate in vesicular stomatitis virus can be explained by a t…
Relationship between within-host fitness and virulence in the vesicular stomatitis virus: correlation with partial decoupling.
2012
ABSTRACT Given the parasitic nature of viruses, it is sometimes assumed that rates of viral replication and dissemination within hosts (within-host fitness) correlate with virulence. However, there is currently little empirical evidence supporting this principle. To test this, we quantified the fitness and virulence of 21 single- or double-nucleotide mutants of the vesicular stomatitis virus in baby hamster kidney cells (BHK-21). We found that, overall, these two traits correlated positively, but significant outliers were identified. Particularly, a single mutation in the conserved C terminus of the N nucleocapsid (U1323A) had a strongly deleterious fitness effect but did not alter or even …
The cost of replication fidelity in human immunodeficiency virus type 1.
2006
Mutation rates should be governed by at least three evolutionary factors: the need for beneficial mutations, the benefit of minimizing the mutational load and the cost of replication fidelity. RNA viruses show high mutation rates compared with DNA micro-organisms, and recent findings suggest that the cost of fidelity might play a role in the evolution of increased mutation rates. Here, by analysing previously published data from HIV-1 reverse transcriptase in vitro assays, we show a trade-off between enzymatic accuracy and the maximum rate of polymerization, thus providing a biochemical basis for the fitness cost of fidelity in HIV-1. This trade-off seems to be related to inefficient exten…
GENOMIC EPIDEMIOLOGY OF TUBERCULOSIS: FROM WITHIN HOST EVOLUTION TO GLOBAL MIGRATION PATTERNS
2018
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