Muller's ratchet with compensatory mutations

TL;DR

This paper models the evolution of deleterious mutations in large populations, showing that compensatory mutations lead to a stable Poisson distribution of mutation load, extending Muller's ratchet theory.

Contribution

It introduces a stochastic differential equation model for Muller's ratchet with compensatory mutations and derives the explicit equilibrium distribution.

Findings

Unique weak solution for the system of equations.

Equilibrium state is a Poisson distribution with specific parameter.

Explicit solution in the infinite population limit.

Abstract

We consider an infinite-dimensional system of stochastic differential equations describing the evolution of type frequencies in a large population. The type of an individual is the number of deleterious mutations it carries, where fitness of individuals carrying k mutations is decreased by \alpha k for some \alpha>0. Along the individual lines of descent, new mutations accumulate at rate \lambda per generation, and each of these mutations has a probability \gamma per generation to disappear. While the case \gamma=0 is known as (the Fleming-Viot version of) Muller's ratchet, the case \gamma>0 is associated with compensatory mutations in the biological literature. We show that the system has a unique weak solution. In the absence of random fluctuations in type frequencies (i.e., for the so-called infinite population limit) we obtain the solution in a closed form by analyzing a probabilistic particle system and show that for \gamma>0, the unique equilibrium state is the Poisson distribution with parameter \lambda/(\gamma+\alpha).