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Measuring Microbial Mutation Rates with the Fluctuation Assay
Published on: November 28, 2019
Two optimal mutation rates in obligate pathogens subject to deleterious mutation
1Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. brendano@u.washington.edu
Journal of Theoretical Biology
|February 5, 2011
Summary
Pathogen mutation rates significantly impact disease spread. High mutation rates can lead to increased pathogen prevalence, but the relationship is complex, with two distinct peaks observed in this study.
Area of Science:
- Evolutionary biology
- Epidemiology
- Microbial genetics
Background:
- Pathogens with high mutation rates accumulate deleterious mutations, reducing their within-host reproductive potential.
- Deleterious mutation load can alter pathogen growth rates, influencing epidemiological factors like prevalence and infection duration.
Purpose of the Study:
- To investigate the complex relationship between pathogen mutation rate and epidemiological properties using an epidemiological model.
- To explore how multiple segregating mutations affecting within-host replication influence disease dynamics.
Main Methods:
- Development and analysis of an epidemiological model incorporating multiple segregating mutations.
- Examination of pathogen mutation rate effects on within-host replication efficiency.
- Stochastic forward simulations to analyze both chronic and acute infection dynamics.
Main Results:
- Two distinct pathogen mutation rates were identified that are associated with high pathogen prevalence.
- Low mutation rate peak: characterized by low genetic diversity, stable prevalence, and inter-host genetic variation.
- High mutation rate peak: exhibited high intra- and inter-host genetic diversity, frequent virulent type invasions, resembling RNA virus quasispecies dynamics.
Conclusions:
- Pathogen mutation rate is a critical factor shaping epidemiological outcomes, with non-linear effects on prevalence.
- A 'valley' in mutation rate exists where selection favors optimal within-host states, potentially increasing virulence and host mortality.
- The study highlights the importance of considering pathogen genetic diversity and mutation dynamics in epidemiological modeling.
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