An approximate stationary solution for multi-allele neutral diffusion with low mutation rates

TL;DR

This paper introduces an approximate method for calculating the stationary distribution of multi-allele neutral diffusion models with low mutation rates, focusing on edge-based line densities to simplify the complex Kolmogorov equation.

Contribution

It provides a practical approximation for slow mutation rates by parameterizing non-reversible rate matrices, facilitating estimation of evolutionary rate matrices from data.

Findings

Approximate solution using line densities along simplex edges.

Method handles non-reversible mutation matrices.

Potential application in estimating evolutionary rates.

Abstract

We address the problem of determining the stationary distribution of the multi-allelic, neutral-evolution Wright-Fisher model in the diffusion limit. A full solution to this problem for an arbitrary K x K mutation rate matrix involves solving for the stationary solution of a forward Kolmogorov equation over a (K - 1)-dimensional simplex, and remains intractable. In most practical situations mutations rates are slow on the scale of the diffusion limit and the solution is heavily concentrated on the corners and edges of the simplex. In this paper we present a practical approximate solution for slow mutation rates in the form of a set of line densities along the edges of the simplex. The method of solution relies on parameterising the general non-reversible rate matrix as the sum of a reversible part and a set of (K - 1)(K - 2)/2 independent terms corresponding to fluxes of probability along closed paths around faces of the simplex. The solution is potentially a first step in estimat- ing non-reversible evolutionary rate matrices from observed allele frequency spectra.