Muller's Ratchet and the Pattern of Variation at a Neutral Locus

Abstract

The levels and patterns of variation at a neutral locus are analyzed in a haploid asexual population undergoing accumulation of deleterious mutations due to Muller's ratchet. We find that the movement of Muller's ratchet can be associated with a considerable reduction in genetic diversity below classical neutral expectation. The extent to which variability is reduced is a function of the deleterious mutation rate, the fitness effects of the mutations, and the population size. Approximate analytical expressions for the expected genetic diversity are compared with simulation results under two different models of deleterious mutations: a model where all deleterious mutations have equal effects and a model where there are two classes of deleterious mutations. We also find that Muller's ratchet can produce a considerable distortion in the neutral frequency spectrum toward an excess of rare variants.

The Structure of Genealogies in the Presence of Purifying Selection: A Fitness-Class Coalescent

“…Note that this calculation is identical to the equivalent distribution of mutation timings computed by Gordo et al (2002) following the approach of Hudson and Kaplan (1994).…”

“…In the following sections of this paper we derive Eq. 1 in the two alternative ways mentioned in the Introduction: by explicitly considering the lineage frequency distribution and by following the path summation method of Hudson and Kaplan (1994), Gordo et al (2002), and Barton and Etheridge (2004).…”

“…Purifying selection acting simultaneously at many linked sites ("background selection") can substantially alter the patterns of molecular variation at these sites, and at linked neutral sites (Etheridge and Griffiths, 2009;Etheridge et al, 2010;Gordo et al, 2002;Hahn, 2008;Hill and Robertson, 1966;Hudson andKaplan, 1994, 1995;Kaplan et al, 1988;McVean and Charlesworth, 2000;O'Fallon et al, 2010;Seger et al, 2010). In recent years, evidence from sequence data points to the general importance of weak selective forces among many linked variants in microbial and viral populations, and on short distance scales in the genomes of sexual organisms (Comeron et al, 2008;Hahn, 2008;Seger et al, 2010).…”

“…This approach was first introduced by Kaplan et al (1988) and Hudson (1990) and further developed by Hudson and Kaplan (1994) and Hudson and Kaplan (1995). It has been the basis for computational methods developed by Gordo et al (2002) and Seger et al (2010) and analytical approaches such as those of Barton and Etheridge (2004), Hermisson et al (2002), andO'Fallon et al (2010).…”

“…This provides a simple intuitive framework for computing the structure of genealogies, but is algebraically involved. The second approach is based on tracing paths in the order that events occur as described by Hudson and Kaplan (1994), and implemented numerically by Gordo et al (2002). This approach has the advantage of algebraic simplicity, and it provides a correspondence between our analytical results and earlier structured coalescent methods.…”