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Vital rates from the action of mutation accumulation

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 Added by Steven N. Evans
 Publication date 2009
  fields Biology
and research's language is English




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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.



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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.
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.
We study evolutionary game dynamics in a well-mixed populations of finite size, N. A well-mixed population means that any two individuals are equally likely to interact. In particular we consider the average abundances of two strategies, A and B, under mutation and selection. The game dynamical interaction between the two strategies is given by the 2x2 payoff matrix [(a,b), (c,d)]. It has previously been shown that A is more abundant than B, if (N-2)a+Nb>Nc+(N-2)d. This result has been derived for particular stochastic processes that operate either in the limit of asymptotically small mutation rates or in the limit of weak selection. Here we show that this result holds in fact for a wide class of stochastic birth-death processes for arbitrary mutation rate and for any intensity of selection.
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 consider a population evolving due to mutation, selection and recombination, where selection includes single-locus terms (additive fitness) and two-loci terms (pairwise epistatic fitness). We further consider the problem of inferring fitness in the evolutionary dynamics from one or several snap-shots of the distribution of genotypes in the population. In the recent literature this has been done by applying the Quasi-Linkage Equilibrium (QLE) regime first obtained by Kimura in the limit of high recombination. Here we show that the approach also works in the interesting regime where the effects of mutations are comparable to or larger than recombination. This leads to a modified main epistatic fitness inference formula where the rates of mutation and recombination occur together. We also derive this formula using by a previously developed Gaussian closure that formally remains valid when recombination is absent. The findings are validated through numerical simulations.
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