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Selection, recombination, and the ancestral initiation graph

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 Added by Frederic Alberti
 Publication date 2021
  fields Biology
and research's language is English




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Recently, the selection-recombination equation with a single selected site and an arbitrary number of neutral sites was solved by means of the ancestral selection-recombination graph. Here, we introduce a more accessible approach, namely the ancestral initiation graph. The construction is based on a discretisation of the selection-recombination equation. We apply our method to systematically explain a long-standing observation concerning the dynamics of linkage disequilibrium between two neutral loci hitchhiking along with a selected one. In particular, this clarifies the nontrivial dependence on the position of the selected site.



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In a (two-type) Wright-Fisher diffusion with directional selection and two-way mutation, let $x$ denote todays frequency of the beneficial type, and given $x$, let $h(x)$ be the probability that, among all individuals of todays population, the individual whose progeny will eventually take over in the population is of the beneficial type. Fearnhead [Fearnhead, P., 2002. The common ancestor at a nonneutral locus. J. Appl. Probab. 39, 38-54] and Taylor [Taylor, J. E., 2007. The common ancestor process for a Wright-Fisher diffusion. Electron. J. Probab. 12, 808-847] obtained a series representation for $h(x)$. We develop a construction that contains elements of both the ancestral selection graph and the lookdown construction and includes pruning of certain lines upon mutation. Besides being interesting in its own right, this construction allows a transparent derivation of the series coefficients of $h(x)$ and gives them a probabilistic meaning.
137 - Sandra Kluth , Ellen Baake 2013
We reconsider the Moran model in continuous time with population size $N$, two allelic types, and selection. We introduce a new particle representation, which we call the labelled Moran model, and which has the same distribution of type frequencies as the original Moran model, provided the initial values are chosen appropriately. In the new model, individuals are labelled $1,2, dots, N$; neutral resampling events may take place between arbitrary labels, whereas selective events only occur in the direction of increasing labels. With the help of elementary methods only, we not only recover fixation probabilities, but also obtain detailed insight into the number and nature of the selective events that play a role in the fixation process forward in time.
We investigate a continuous time, probability measure-valued dynamical system that describes the process of mutation-selection balance in a context where the population is infinite, there may be infinitely many loci, and there are weak assumptions on selective costs. Our model arises when we incorporate very general recombination mechanisms into a previous model of mutation and selection from Steinsaltz, Evans and Wachter (2005) and take the relative strength of mutation and selection to be sufficiently small. The resulting dynamical system is a flow of measures on the space of loci. Each such measure is the intensity measure of a Poisson random measure on the space of loci: the points of a realization of the random measure record the set of loci at which the genotype of a uniformly chosen individual differs from a reference wild type due to an accumulation of ancestral mutations. Our motivation for working in such a general setting is to provide a basis for understanding mutation-driven changes in age-specific demographic schedules that arise from the complex interaction of many genes, and hence to develop a framework for understanding the evolution of aging. We establish the existence and uniqueness of the dynamical system, provide conditions for the existence and stability of equilibrium states, and prove that our continuous-time dynamical system is the limit of a sequence of discrete-time infinite population mutation-selection-recombination models in the standard asymptotic regime where selection and mutation are weak relative to recombination and both scale at the same infinitesimal rate in the limit.
We study a continuous-time dynamical system that models the evolving distribution of genotypes in an infinite population where genomes may have infinitely many or even a continuum of loci, mutations accumulate along lineages without back-mutation, added mutations reduce fitness, and recombination occurs on a faster time scale than mutation and selection. Some features of the model, such as existence and uniqueness of solutions and convergence to the dynamical system of an approximating sequence of discrete time models, were presented in earlier work by Evans, Steinsaltz, and Wachter for quite general selective costs. Here we study a special case where the selective cost of a genotype with a given accumulation of ancestral mutations from a wild type ancestor is a sum of costs attributable to each individual mutation plus successive interaction contributions from each $k$-tuple of mutations for $k$ up to some finite ``degree. Using ideas from complex chemical reaction networks and a novel Lyapunov function, we establish that the phenomenon of mutation-selection balance occurs for such selection costs under mild conditions. That is, we show that the dynamical system has a unique equilibrium and that it converges to this equilibrium from all initial conditions.
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