Mutational Meltdown in Laboratory Yeast Populations

Abstract

In small or repeatedly bottlenecked populations, mutations are expected to accumulate by genetic drift, causing fitness declines. In mutational meltdown models, such fitness declines further reduce population size, thus accelerating additional mutation accumulation and leading to extinction. Because the rate of mutation accumulation is determined partly by the mutation rate, the risk and rate of meltdown are predicted to increase with increasing mutation rate. We established 12 replicate populations of Saccharomyces cerevisiae from each of two isogenic strains whose genomewide mutation rates differ by approximately two orders of magnitude. Each population was transferred daily by a fixed dilution that resulted in an effective population size near 250. Fitness declines that reduce growth rates were expected to reduce the numbers of cells transferred after dilution, thus reducing population size and leading to mutational meltdown. Through 175 daily transfers and approximately 2900 generations, two extinctions occurred, both in populations with elevated mutation rates. For one of these populations there is direct evidence that extinction resulted from mutational meltdown: Extinction immediately followed a major fitness decline, and it recurred consistently in replicate populations reestablished from a sample frozen after this fitness decline, but not in populations founded from a predecline sample. Wild-type populations showed no trend to decrease in size and, on average, they increased in fitness.

dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants

“…Although theory and experimental evidence indicate that haploid and diploid mutator cells evolve more rapidly than nonmutators (2,(80)(81)(82)(83)(84)(85)(86)88), prolonged expression of a strong mutator phenotype can also drive extinction (18,19,89,90). We recently empirically defined the maximum mutation rate of diploid yeast (20) using combinations of mutator alleles.…”

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.…”

Accumulation of Deleterious Mutations in Small Abiotic Populations of RNA

“…Eventually a threshold is crossed, and the population spirals into extinction via a ''mutational meltdown,'' as can be seen in ciliated protozoans and fibroblast cultures, for example (Smith and Pereira-Smith 1977;Tagaki and Yoshida 1980). Mutation-accumulation (MA) experiments have been used effectively for .40 years to address questions related to the buildup of deleterious mutations in populations such as those of Arabidopsis, Caenorhabditis elegans, Daphnia, Drosophila, Escherichia coli, Saccharomyces cerevisiae, and others (reviewed in Mukai 1964;Kibota and Lynch 1996;Lynch and Walsh 1998;Schultz et al 1999;Pfrender and Lynch 2000;Zeyl et al 2001;Estes et al 2004). A species lineage is propagated in a very controlled environment over a large number of generations and is typically forced through a bottleneck in size each generation to exacerbate the effects of random genetic drift.…”