Muller's ratchet decreases fitness of a DNA-based microbe.

Abstract

Muller proposed that an asexual organism will inevitably accumulate deleterious mutations, resulting in an increase of the mutational load and an inexorable, ratchetlike, loss of the least mutated class [Muller, H. J. (1964) Mutat. Res. 1,[2][3][4][5][6][7][8][9]. The operation of Muller's ratchet on real populations has been experimentally demonstrated only in RNA viruses. However, these cases are exceptional in that the mutation rates of the RNA viruses are extremely high. We have examined whether Muller's ratchet operates in Salmonella typhimurium, a DNA-based organism with a more typical genomic mutation rate. Cells were grown asexually under conditions expected to result in high genetic drift, and the increase in mutational load was determined. S. typhimurium accumulated mutations under these conditions such that after 1700 generations, 1% of the 444 lineages tested had suffered an obvious loss of fitness, as determined by decreased growth rate. These results suggest that in the absence of sex and with high genetic drift, genetic mechanisms, such as back or compensatory mutations, cannot compensate for the accumulation of deleterious mutations. In addition, we measured the appearance of auxotrophs, which allowed us to calculate an average spontaneous mutation rate of approximately 0.3-1.5x 10-9 mutations per base pair per generation. This rate is measured for the largest genetic target studied so far, a collection of about 200 genes.Sex is genetically and ecologically an expensive and cumbersome means of reproduction, suggesting that it must provide some significant advantage(s) for those systems which utilize it (see, for example, refs. 1-3). One of several theories which have been proposed to explain the prevalence of sex is that sex may rearrange the genetic load in the population to continually generate some individuals with a fit combination of alleles. This theory is encapsulated in the hypothesis known as Muller's ratchet (4, 5). According to this hypothesis, the accumulation of deleterious mutations can lead to the loss of the most fit (mutation-free) class from a population. Muller (4) noted that this problem is most acute in asexual lines of descent. This problem will be exacerbated by high mutation rates and by small population sizes. Such lineages will accumulate deleterious mutations, and in a population of finite size, genetic drift will inevitably result in the irreversible loss of the least mutated class, unless back mutations occur at a high rate. As a result, the mutational load will increase in a rachet-like manner with the successive loss of the least mutated class. For any particular set of circumstances, the effects of Muller's ratchet can be slowed or stopped four different ways: (i) Increasing population size minimizes the effects of the ratchet by allowing selection to operate on the individuals that escape deleterious mutation, ensuring that the least mutated class is always present. (ii) Reducing the mutation rate decreases the accumulation of added load and makes it mor...

Dynamic Mutation–Selection Balance as an Evolutionary Attractor

“…The repetitive action of the ratchet leads to the accumulation of deleterious mutations, despite the action of purifying selection. This ratchet effect has been extensively analyzed (Gessler 1995;Charlesworth and Charlesworth 1997;Gordo and Charlesworth 2000a,b;) and has been observed in experiments (Chao 1990;Duarte et al 1992;Andersson and Hughes 1996;Zeyl et al 2001) and in nature (Rice 1994;Lynch 1996;Howe and Denver 2008). In small populations when deleterious mutation rates are high or selection pressures are weak, the ratchet can proceed quickly, causing rapid degradation of asexual genomes Lynch et al , 1995.…”

Lethal Mutagenesis in Viruses and Bacteria

“…The effect has frequently been described within the paradigm of Muller's ratchet (Muller 1964;Haigh 1978;Andersson and Hughes 1996), where the genome of an asexual organism accumulates stochastic deleterious mutations in an irreversible manner, leading to the systematic decrease in the fitness of the organism. The concept of Muller's ratchet applies to finite, asexual populations.…”

Evidence of Muller’s ratchet in herpes simplex virus type 1

“…Its operation has found experimental confirmation mainly in studies carried out with RNA viruses (Chao, 1990; Clarke et al, 1993;de la Iglesia & Elena, 2007;Duarte et al, 1992Duarte et al, , 1994Escarmís et al, 1996Escarmís et al, , 2009Novella, 2004; Novella & EbendickCorpus, 2004; reviewed by Escarmís et al, 2006), and also with plants, protozoa, mitochondrial DNA and bacteria (Allen et al, 2009;Andersson & Hughes, 1996;Bell, 1988;Coates, 1992; Engelstädter, 2008;Loewe, 2006;Moran, 1996). The effects of Muller's ratchet are accentuated when an asexual genome population undergoes severe bottleneck events.…”