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The transition distribution of a sample from a Wright-Fisher diffusion with general small mutation rates

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 Added by Conrad Burden
 Publication date 2018
  fields Biology
and research's language is English




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The transition distribution of a sample taken from a Wright-Fisher diffusion with general small mutation rates is found using a coalescent approach. The approximation is equivalent to having at most one mutation in the coalescent tree of the sample up to the most recent common ancestor with additional mutations occurring on the lineage from the most recent common ancestor to the time origin if complete coalescence occurs before the origin. The sampling distribution leads to an approximation for the transition density in the diffusion with small mutation rates. This new solution has interest because the transition density in a Wright-Fisher diffusion with general mutation rates is not known.



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The stationary distribution of a sample taken from a Wright-Fisher diffusion with general small mutation rates is found using a coalescent approach. The approximation is equivalent to having at most one mutation in the coalescent tree to the first order in the rates. The sample probabilities characterize an approximation for the stationary distribution from the Wright-Fisher diffusion. The approach is different from Burden and Tang (2016,2017) who use a probability flux argument to obtain the same results from a forward diffusion generator equation. The solution has interest because the solution is not known when rates are not small. An analogous solution is found for the configuration of alleles in a general exchangeable binary coalescent tree. In particular an explicit solution is found for a pure birth process tree when individuals reproduce at rate lambda.
The stationary distribution of the diffusion limit of the 2-island, 2-allele Wright-Fisher with small but otherwise arbitrary mutation and migration rates is investigated. Following a method developed by Burden and Tang (2016, 2017) for approximating the forward Kolmogorov equation, the stationary distribution is obtained to leading order as a set of line densities on the edges of the sample space, corresponding to states for which one island is bi-allelic and the other island is non-segregating, and a set of point masses at the corners of the sample space, corresponding to states for which both islands are simultaneously non-segregating. Analytic results for the corner probabilities and line densities are verified independently using the backward generator and for the corner probabilities using the coalescent.
We investigate the properties of a Wright-Fisher diffusion process started from frequency x at time 0 and conditioned to be at frequency y at time T. Such a process is called a bridge. Bridges arise naturally in the analysis of selection acting on standing variation and in the inference of selection from allele frequency time series. We establish a number of results about the distribution of neutral Wright-Fisher bridges and develop a novel rejection sampling scheme for bridges under selection that we use to study their behavior.
Duality plays an important role in population genetics. It can relate results from forwards-in-time models of allele frequency evolution with those of backwards-in-time genealogical models; a well known example is the duality between the Wright-Fisher diffusion for genetic drift and its genealogical counterpart, the coalescent. There have been a number of articles extending this relationship to include other evolutionary processes such as mutation and selection, but little has been explored for models also incorporating crossover recombination. Here, we derive from first principles a new genealogical process which is dual to a Wright-Fisher diffusion model of drift, mutation, and recombination. Our approach is based on expressing a putative duality relationship between two models via their infinitesimal generators, and then seeking an appropriate test function to ensure the validity of the duality equation. This approach is quite general, and we use it to find dualities for several important variants, including both a discrete L-locus model of a gene and a continuous model in which mutation and recombination events are scattered along the gene according to continuous distributions. As an application of our results, we derive a series expansion for the transition function of the diffusion. Finally, we study in further detail the case in which mutation is absent. Then the dual process describes the dispersal of ancestral genetic material across the ancestors of a sample. The stationary distribution of this process is of particular interest; we show how duality relates this distribution to haplotype fixation probabilities. We develop an efficient method for computing such probabilities in multilocus models.
279 - Joshua G. Schraiber 2013
The Wright-Fisher process with selection is an important tool in population genetics theory. Traditional analysis of this process relies on the diffusion approximation. The diffusion approximation is usually studied in a partial differential equations framework. In this paper, I introduce a path integral formalism to study the Wright-Fisher process with selection and use that formalism to obtain a simple perturbation series to approximate the transition density. The perturbation series can be understood in terms of Feynman diagrams, which have a simple probabilistic interpretation in terms of selective events. The perturbation series proves to be an accurate approximation of the transition density for weak selection and is shown to be arbitrarily accurate for any selection coefficient.
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