Vázquez-Mendoza, I.; Rodríguez-Torres, E.E.; Ezadian, M.; Wahl, L.M.; Gerrish, P.J. Estimating the Rate of Mutation to a Mutator Phenotype. Axioms 2024, 13, 117, doi:10.3390/axioms13020117.
Vázquez-Mendoza, I.; Rodríguez-Torres, E.E.; Ezadian, M.; Wahl, L.M.; Gerrish, P.J. Estimating the Rate of Mutation to a Mutator Phenotype. Axioms 2024, 13, 117, doi:10.3390/axioms13020117.
Vázquez-Mendoza, I.; Rodríguez-Torres, E.E.; Ezadian, M.; Wahl, L.M.; Gerrish, P.J. Estimating the Rate of Mutation to a Mutator Phenotype. Axioms 2024, 13, 117, doi:10.3390/axioms13020117.
Vázquez-Mendoza, I.; Rodríguez-Torres, E.E.; Ezadian, M.; Wahl, L.M.; Gerrish, P.J. Estimating the Rate of Mutation to a Mutator Phenotype. Axioms 2024, 13, 117, doi:10.3390/axioms13020117.
Abstract
Somerateofmutationisinevitable,eveningenesthatthemselvesdeterminethemutation rate. Because mutation in these genes can alter the mutation rate, variation in the mutation rate is inevitable. This simple line of reasoning is corroborated by a handful of empirical studies that found mutation-rate variation in natural and laboratory populations. The evolutionary consequences of mutation-rate variation in natural populations can be many and can be difficult to predict, as selection on such variation can be both direct and indirect. For example, lineages with increased mutation rate will have increased adaptability in the long term but decreased overall fitness in the short term because most fitness mutations are immediately deleterious. In spite of its great relevance to basic and applied science, the rate of mutation to mutator phenotype continues to be essentially unknown. The reasons for this gap in our knowledge are largely methodological; in general, a mutator phenotype cannot be observed directly but must instead be inferred from numbers of some neutral “marker” mutation that can be observed directly: different mutation-rate variants will produce this marker mutation at different rates. Here, we derive the expected distribution of numbers of the marker mutants observed, accounting for the fact that some of the mutants will have been produced by a mutator phenotype that itself arose by mutation during the growth of the culture. This development makes possible a novel experimental protocol for estimating the rate of mutation to mutator phenotype. Simulated experiments using biologically-reasonable parameters that employ this protocol show that such experiments in the lab can give us fairly accurate estimates of the rate of mutation to mutator phenotype. Although our ability to estimate mutation-to-mutator rates from simulated experiments is promising, we view this study as a proof-of-concept study and only a first step towards practical empirical estimation.
Biology and Life Sciences, Ecology, Evolution, Behavior and Systematics
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