Lethal mutagenesis and evolutionary epidemiology
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Lethal mutagenesis and evolutionary epidemiology
The lethal mutagenesis hypothesis states that within-host populations of pathogens can be driven to extinction when the load of deleterious mutations is artificially increased with a mutagen, and becomes too high for the population to be maintained. Although chemical mutagens have been shown to lead to important reductions in viral titres for a wide variety of RNA viruses, the theoretical under...
متن کاملLethal mutagenesis of bacteria.
Lethal mutagenesis, the killing of a microbial pathogen with a chemical mutagen, is a potential broad-spectrum antiviral treatment. It operates by raising the genomic mutation rate to the point that the deleterious load causes the population to decline. Its use has been limited to RNA viruses because of their high intrinsic mutation rates. Microbes with DNA genomes, which include many viruses a...
متن کاملLethal mutagenesis in viruses and bacteria.
In this work we study how mutations that change physical properties of cell proteins (stability) affect population survival and growth. We present a model in which the genotype is presented as a set folding free energies of cell proteins. Mutations occur upon replication, so stabilities of some proteins in daughter cells differ from those in the parent cell by amounts deduced from the distribut...
متن کاملTheory of lethal mutagenesis for viruses.
Mutation is the basis of adaptation. Yet, most mutations are detrimental, and elevating mutation rates will impair a population's fitness in the short term. The latter realization has led to the concept of lethal mutagenesis for curing viral infections, and work with drugs such as ribavirin has supported this perspective. As yet, there is no formal theory of lethal mutagenesis, although referen...
متن کاملEvolutionary Search in Lethal Environments
In Natural evolution, a mutation may be lethal, causing an abrupt end to an evolving lineage. This fact has a tendency to cause evolution to “prefer” mutationally robust solutions (which can in turn slow innovation), an effect that has been studied previously, especially in the context of evolution on neutral plateaux. Here, we tackle related issues but from the perspective of a practical optim...
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ژورنال
عنوان ژورنال: Philosophical Transactions of the Royal Society B: Biological Sciences
سال: 2010
ISSN: 0962-8436,1471-2970
DOI: 10.1098/rstb.2010.0058