Abstract:Using a previously undescribed approach, we develop an analytic model that predicts whether an asexual population accumulates advantageous or deleterious mutations over time and the rate at which either process occurs. The model considers a large number of linked identical loci, or nucleotide sites; assumes that the selection coefficient per site is much less than the mutation rate per genome; and includes back and compensating mutations. Using analysis and Monte Carlo simulations, we demonstrate the accuracy … Show more
“…Under this assumption a deterministic description suffices and we can write down the time evolution equation for the average population fraction X(σ, t) of sequence σ at time t. Although this is often unrealistic, the analysis is simpler in this limit which in many cases can be adapted to the finite population case to provide quantitative agreement with experiments [25,26,27]. The infinite population limit can be justified if the population is known to be localized in a small region of sequence space around a fitness peak, if one is interested in a short piece of the genome such as a single regulatory binding site [16] (see also Sect.…”
Section: Mutation-selection Modelsmentioning
confidence: 99%
“…Note that the model is well defined only for N µ < 1. At large times, Z(σ, t + 1) ≈ ΛZ(σ, t) where Λ is the largest eigenvalue of the evolution matrix on the right hand side of (27). In the delocalised phase, the population is spread over the entire sequence space with mean fitness W = 1, so that Λ = 1 whereas in the localised phase, a finite fraction has fitness W 0 > 1 and hence Λ > 1.…”
Section: Exact Solution Of a Sharp Peak Modelmentioning
confidence: 99%
“…In addition, the continuum limit of (75) should be carried out on the level of ln Y rather than for Y itself, which leads to a nonlinear drift-diffusion equation replacing (76) [27]. Recent applications of fitness space models that go beyond the present discussion include studies of the in vitro evolution of DNA sequences selected for protein binding [46], viral populations undergoing serial population transfers [91], and the effects of recombination in asexual populations [92].…”
Section: Dynamics In Smooth Fitness Landscapesmentioning
confidence: 99%
“…Finally, we note that under certain conditions populations of RNA viruses display a linear increase or decrease of fitness with time [27,110], which can be analyzed within the framework of the fitness space models discussed in Sect. 5.3.…”
Section: Dynamics Of Microbial Evolutionmentioning
“…Under this assumption a deterministic description suffices and we can write down the time evolution equation for the average population fraction X(σ, t) of sequence σ at time t. Although this is often unrealistic, the analysis is simpler in this limit which in many cases can be adapted to the finite population case to provide quantitative agreement with experiments [25,26,27]. The infinite population limit can be justified if the population is known to be localized in a small region of sequence space around a fitness peak, if one is interested in a short piece of the genome such as a single regulatory binding site [16] (see also Sect.…”
Section: Mutation-selection Modelsmentioning
confidence: 99%
“…Note that the model is well defined only for N µ < 1. At large times, Z(σ, t + 1) ≈ ΛZ(σ, t) where Λ is the largest eigenvalue of the evolution matrix on the right hand side of (27). In the delocalised phase, the population is spread over the entire sequence space with mean fitness W = 1, so that Λ = 1 whereas in the localised phase, a finite fraction has fitness W 0 > 1 and hence Λ > 1.…”
Section: Exact Solution Of a Sharp Peak Modelmentioning
confidence: 99%
“…In addition, the continuum limit of (75) should be carried out on the level of ln Y rather than for Y itself, which leads to a nonlinear drift-diffusion equation replacing (76) [27]. Recent applications of fitness space models that go beyond the present discussion include studies of the in vitro evolution of DNA sequences selected for protein binding [46], viral populations undergoing serial population transfers [91], and the effects of recombination in asexual populations [92].…”
Section: Dynamics In Smooth Fitness Landscapesmentioning
confidence: 99%
“…Finally, we note that under certain conditions populations of RNA viruses display a linear increase or decrease of fitness with time [27,110], which can be analyzed within the framework of the fitness space models discussed in Sect. 5.3.…”
Section: Dynamics Of Microbial Evolutionmentioning
“…For asexual models of this type, the dynamics are fairly easily solved for very small populations or for infinite populations. However, even with very simple assumptions regarding the fitness landscape, the evolution dynamics of a large but finite population far from equilibrium turned out to be a difficult problem, as the evolution rate diverges for large populations [9]; only recently have general analytical results emerged [10].…”
Recent studies of in vitro evolution of DNA via protein binding indicate that the evolution behavior is qualitatively different in different parameter regimes. I here present a general theory that is valid for a wide range of parameters, and which reproduces and extends previous results. Specifically, the mean-field theory of a general translation-invariant model can be reduced to the basic diffusion equation with a dynamic boundary condition. The simple analytical form yields both quantitatively accurate predictions and valuable insight into the principles involved. In particular, I introduce a cutoff criterion for finite populations that illustrates both of these qualities.
Despite several decades of computational and experimental work across many systems, evolvability remains on the periphery with regards to its status as a widely accepted and regularly applied theoretical concept. Here we propose that its marginal status is partly a result of large gaps between the diverse but disconnected theoretical treatments of evolvability and the relatively narrower range of studies that have tested it empirically. To make this case, we draw on a range of examples—from experimental evolution in microbes, to molecular evolution in proteins—where attempts have been made to mend this disconnect. We highlight some examples of progress that has been made and point to areas where synthesis and translation of existing theory can lead to further progress in the still‐new field of empirical measurements of evolvability.
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