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Information Geometry and the Wright-Fisher model of Mathematical Population GeneticsTran, Tat Dat 31 July 2012 (has links) (PDF)
My thesis addresses a systematic approach to stochastic models in population genetics; in particular, the Wright-Fisher models affected only by the random genetic drift. I used various mathematical methods such as Probability, PDE, and Geometry to answer an important question: \"How do genetic change factors (random genetic drift, selection, mutation, migration, random environment, etc.) affect the behavior of gene frequencies or genotype frequencies in generations?”.
In a Hardy-Weinberg model, the Mendelian population model of a very large number of individuals without genetic change factors, the answer is simple by the Hardy-Weinberg principle: gene frequencies remain unchanged from generation to generation, and genotype frequencies from the second generation onward remain also unchanged from generation to generation.
With directional genetic change factors (selection, mutation, migration), we will have a deterministic dynamics of gene frequencies, which has been studied rather in detail. With non-directional genetic change factors (random genetic drift, random environment), we will have a stochastic dynamics of gene frequencies, which has been studied with much more interests. A combination of these factors has also been considered.
We consider a monoecious diploid population of fixed size N with n + 1 possible alleles at a given locus A, and assume that the evolution of population was only affected by the random genetic drift. The question is that what the behavior of the distribution of relative frequencies of alleles in time and its stochastic quantities are.
When N is large enough, we can approximate this discrete Markov chain to a continuous Markov with the same characteristics. In 1931, Kolmogorov first introduced a nice relation between a continuous Markov process and diffusion equations. These equations called the (backward/forward) Kolmogorov equations which have been first applied in population genetics in 1945 by Wright.
Note that these equations are singular parabolic equations (diffusion coefficients vanish on boundary). To solve them, we use generalized hypergeometric functions. To know more about what will happen after the first exit time, or more general, the behavior of whole process, in joint work with J. Hofrichter, we define the global solution by moment conditions; calculate the component solutions by boundary flux method and combinatorics method.
One interesting property is that some statistical quantities of interest are solutions of a singular elliptic second order linear equation with discontinuous (or incomplete) boundary values. A lot of papers, textbooks have used this property to find those quantities. However, the uniqueness of these problems has not been proved. Littler, in his PhD thesis in 1975, took up the uniqueness problem but his proof, in my view, is not rigorous. In joint work with J. Hofrichter, we showed two different ways to prove the uniqueness rigorously. The first way is the approximation method. The second way is the blow-up method which is conducted by J. Hofrichter.
By applying the Information Geometry, which was first introduced by Amari in 1985, we see that the local state space is an Einstein space, and also a dually flat manifold with the Fisher metric; the differential operator of the Kolmogorov equation is the affine Laplacian which can be represented in various coordinates and on various spaces. Dynamics on the whole state space explains some biological phenomena.
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Information Geometry and the Wright-Fisher model of Mathematical Population GeneticsTran, Tat Dat 04 July 2012 (has links)
My thesis addresses a systematic approach to stochastic models in population genetics; in particular, the Wright-Fisher models affected only by the random genetic drift. I used various mathematical methods such as Probability, PDE, and Geometry to answer an important question: \"How do genetic change factors (random genetic drift, selection, mutation, migration, random environment, etc.) affect the behavior of gene frequencies or genotype frequencies in generations?”.
In a Hardy-Weinberg model, the Mendelian population model of a very large number of individuals without genetic change factors, the answer is simple by the Hardy-Weinberg principle: gene frequencies remain unchanged from generation to generation, and genotype frequencies from the second generation onward remain also unchanged from generation to generation.
With directional genetic change factors (selection, mutation, migration), we will have a deterministic dynamics of gene frequencies, which has been studied rather in detail. With non-directional genetic change factors (random genetic drift, random environment), we will have a stochastic dynamics of gene frequencies, which has been studied with much more interests. A combination of these factors has also been considered.
We consider a monoecious diploid population of fixed size N with n + 1 possible alleles at a given locus A, and assume that the evolution of population was only affected by the random genetic drift. The question is that what the behavior of the distribution of relative frequencies of alleles in time and its stochastic quantities are.
When N is large enough, we can approximate this discrete Markov chain to a continuous Markov with the same characteristics. In 1931, Kolmogorov first introduced a nice relation between a continuous Markov process and diffusion equations. These equations called the (backward/forward) Kolmogorov equations which have been first applied in population genetics in 1945 by Wright.
Note that these equations are singular parabolic equations (diffusion coefficients vanish on boundary). To solve them, we use generalized hypergeometric functions. To know more about what will happen after the first exit time, or more general, the behavior of whole process, in joint work with J. Hofrichter, we define the global solution by moment conditions; calculate the component solutions by boundary flux method and combinatorics method.
One interesting property is that some statistical quantities of interest are solutions of a singular elliptic second order linear equation with discontinuous (or incomplete) boundary values. A lot of papers, textbooks have used this property to find those quantities. However, the uniqueness of these problems has not been proved. Littler, in his PhD thesis in 1975, took up the uniqueness problem but his proof, in my view, is not rigorous. In joint work with J. Hofrichter, we showed two different ways to prove the uniqueness rigorously. The first way is the approximation method. The second way is the blow-up method which is conducted by J. Hofrichter.
By applying the Information Geometry, which was first introduced by Amari in 1985, we see that the local state space is an Einstein space, and also a dually flat manifold with the Fisher metric; the differential operator of the Kolmogorov equation is the affine Laplacian which can be represented in various coordinates and on various spaces. Dynamics on the whole state space explains some biological phenomena.
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