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Kenneth W. Wachter

Publications and source records attributed to Kenneth W. Wachter.

4 recordsLinked to original sources

A mutation-selection model for general genotypes with recombination

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.

q-bio.PE

Vital rates from the action of mutation accumulation

New models for evolutionary processes of mutation accumulation allow hypotheses about the age-specificity of mutational effects to be translated into predictions of heterogeneous population hazard functions. We apply these models to questions in the biodemography of longevity, including proposed explanations of Gompertz hazards and mortality plateaus, and use them to explore the possibility of melding evolutionary and functional models of aging.

q-bio.PE

The Age-Specific Force of Natural Selection and Walls of Death

W. D. Hamilton's celebrated formula for the age-specific force of natural selection furnishes predictions for senescent mortality due to mutation accumulation, at the price of reliance on a linear approximation. Applying to Hamilton's setting the full non-linear demographic model for mutation accumulation of Evans et al. (2007), we find surprising differences. Non-linear interactions cause the collapse of Hamilton-style predictions in the most commonly studied case, refine predictions in other cases, and allow Walls of Death at ages before the end of reproduction. Haldane's Principle for genetic load has an exact but unfamiliar generalization.

q-bio.PE

A generalized model of mutation-selection balance with applications to aging

A probability model is presented for the dynamics of mutation-selection balance in a haploid infinite-population infinite-sites setting sufficiently general to cover mutation-driven changes in full age-specific demographic schedules. The model accommodates epistatic as well as additive selective costs. Closed form characterizations are obtained for solutions in finite time, along with proofs of convergence to stationary distributions and a proof of the uniqueness of solutions in a restricted case. Examples are given of applications to the biodemography of aging, including instabilities in current formulations of mutation accumulation.

q-bio.PE