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Madgwick, P. G.

Publications and source records attributed to Madgwick, P. G..

2 recordsLinked to original sources

A synoptic solution to a Wright-Fisher model with recurrent mutation, drift and selection

The time to fixation (conditional upon fixation) and probability of fixation are key summary statistics of classical population genetics. Here, they are integrated to solve the time to fixation unconditional on fixation in a Wright-Fisher model with recurrent mutation, drift and selection. In its derivation, minor improvements to the probability of fixation and the probability distributions of emergence and spread (or passage) are made. The solution is an exponentially modified Gaussian (ex-Gaussian) distribution with a mean and variance that is the sum of the mean and variance of the underlying exponential and normal (i.e. Gaussian) distributions. To demonstrate its value as a synoptic solution to the Wright-Fisher model, the ex-Gaussian distribution is used to partition the effects of the evolutionary forces of mutation, drift, selection and (to some extent) migration on chosen points of the probability distribution of fixation times. Further, the solution is used to derive (and show the quantitative meaning of) the stochastic drift barrier to nearly neutral mutations with very low selection coefficients, and its consequences on the probability distribution of phenotypic and/or fitness effects that contribute to adaptation. In this way, the probability distribution of the time to fixation unconditional on fixation provides an elegant summary of some key results from classical population genetics, and is also likely to have many other theoretical and applied uses.

evolutionary biology↗

Tuning Spatial Distributions of Selection Pressure to Suppress Emergence of Resistance

Control measures such as insecticides or antimicrobials are used to contain biological agents such as pathogenic bacteria and vectors of human and plant diseases, respectively. Following control measure application, a resistant subpopulation may eventually rise to such frequency that the control measure will be rendered ineffective: The timescale over which this occurs is the effective lifetime of the control measure. Prolonging this timescale relaxes urgency at which novel control measure needs to be developed. Spatial heterogeneity in control measure application can influence the rate at which resistance to the control measure evolves; in the agricultural context, this fact is exploited by distributing insecticides in mosaics across cropping regions in order to slow the rate of resistance evolution. Contemporary and historical modeling practices, which aim to inform agricultural practices, often employ assumptions which squeeze out the impact of the spatio-temporal heterogeneity endemic to nature. In this paper, we present a minimal model of continuous dispersal and spatio-temporal heterogeneity in selection pressure distribution which exhibits a novel dynamic: The spatial distribution of selection pressure may be tuned in order to minimize the initial rate at which resistance evolves, thus increasing the effective lifetime of a pesticide. Author summaryThere are many contexts in which humans apply control measures to biological agents: pesticides are applied in fields to kill the pests that damage crops, mosquito nests are distributed to prevent the spread of malaria, and cancer drugs are applied to kill off tumors in humans. These control measures are examples of selection pressures, which select against strains which are susceptible to them. If a mutation occurs which confers resistance, the control agent will select for the resistant strain, thus reducing the efficacy of the control agent as the frequency of resistance increases in the population. This necessitates more of the control agent to be applied, or for a novel control agent to be developed. The former may have unintended consequences on the local environment, and the latter is expensive and time-intensive. It is preferable to carefully tune how the control agent is applied - perhaps instead of one massive compact region of control measure application, it is better to apply the control measure over multiple smaller regions? Here, we use a toy model of motile organisms to demonstrate that an optimal distribution exists for a variety of scenarios.

evolutionary biology↗