2019
DOI: 10.1101/794867
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Range expansion shifts clonal interference patterns in evolving populations

Abstract: The movement of a population through space can have profound impacts on its evolution, as observed theoretically, experimentally, and clinically. Furthermore, it has been observed that mutants emerging at the spreading front develop higher frequencies in the population than their counterparts further from the front. Here we use fundamental arguments from population genetics regarding expected time scales of beneficial mutant establishment and fixation in a population undergoing range expansion to characterize … Show more

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Cited by 5 publications
(4 citation statements)
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“…We assume that selection under drug therapy represents a strong-selection and weak mutation regime in order to compute transition matrices for our models. It is likely that other selection regimes emerge in cases of real-world pharmacokinetics or spatial regimes where the drug concentration fluctuates dramatically ( 54 , 55 ). While we relax some of the strongest assumptions in the SSWM regime via a previously studied phenomenological model ( 27 , 56 ), we still do not capture the possibility of deleterious or multiple simultaneous mutations to fix.…”
Section: Discussionmentioning
confidence: 99%
“…We assume that selection under drug therapy represents a strong-selection and weak mutation regime in order to compute transition matrices for our models. It is likely that other selection regimes emerge in cases of real-world pharmacokinetics or spatial regimes where the drug concentration fluctuates dramatically ( 54 , 55 ). While we relax some of the strongest assumptions in the SSWM regime via a previously studied phenomenological model ( 27 , 56 ), we still do not capture the possibility of deleterious or multiple simultaneous mutations to fix.…”
Section: Discussionmentioning
confidence: 99%
“…We assume that selection under drug therapy represents a strong-selection and weak mutation regime in order to compute transition matrices for our models. While this is likely true in most cases, it is possible that other selection regimes emerge in cases of real world pharmacokinetics or spatial regimes where the drug concentration fluctuates dramatically 48,49 . In addition, we chose to keep drug concentration constant throughout are analysis, largely owing to the lack of robust empirical data linking genotype to phenotype under dose varying conditions (sometimes called a fitness seascape) 50 .…”
Section: Discussionmentioning
confidence: 99%
“…This occurs in the large population, frequent mutation regime: if the typical mutation rate scale is µ, meaning m βα ∼ O(µ) for all nonzero mutation rates where α = β, then this corresponds to µN 1, N 1 [37][38][39][40] . In this regime multiple genotypes can generally coexist in the population at equilibrium (though one may be quite dominant), which is particularly relevant for pathogenic populations, especially ones spreading through space [41][42][43] . Remarkably, there is a simple analytical expression that provides an excellent approximation to s λ(t),…”
Section: /19mentioning
confidence: 99%