Frequency of fixation of adaptive mutations is higher in evolving diploid than haploid yeast populations

Paquin, Charlotte E.; Adams, Julian

doi:10.1038/302495a0

Cited by 214 publications

(188 citation statements)

References 37 publications

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“…A second implication of our results is that antifungal loid advantages in the rate of adaptation. For example, diploid populations had a clear advantage over haploid drugs could potentially be deployed to manage resistance in fungal pathogens if the fitness effects of their populations in adapting to glucose limitation in chemostats (Paquin and Adams 1983), while haploid popularesistance mutations in the host mirror those of S. cerevisiae seen here. For example, as noted above, haploid tions had at least a transient advantage over diploid populations in adapting to a minimal medium in serially populations may be expected to evolve high resistance in one step in high drug concentrations through loss transferred batch cultures (Zeyl et al 2003).…”

Section: Discussionmentioning

confidence: 80%

Haploidy, Diploidy and Evolution of Antifungal Drug Resistance in Saccharomyces cerevisiae

2004

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We tested the hypothesis that the time course of the evolution of antifungal drug resistance depends on the ploidy of the fungus. The experiments were designed to measure the initial response to the selection imposed by the antifungal drug fluconazole up to and including the fixation of the first resistance mutation in populations of Saccharomyces cerevisiae. Under conditions of low drug concentration, mutations in the genes PDR1 and PDR3, which regulate the ABC transporters implicated in resistance to fluconazole, are favored. In this environment, diploid populations of defined size consistently became fixed for a resistance mutation sooner than haploid populations. Experiments manipulating population sizes showed that this advantage of diploids was due to increased mutation availability relative to that of haploids; in effect, diploids have twice the number of mutational targets as haploids and hence have a reduced waiting time for mutations to occur. Under conditions of high drug concentration, recessive mutations in ERG3, which result in resistance through altered sterol synthesis, are favored. In this environment, haploids consistently achieved resistance much sooner than diploids. When 29 haploid and 29 diploid populations were evolved for 100 generations in low drug concentration, the mutations fixed in diploid populations were all dominant, while the mutations fixed in haploid populations were either recessive (16 populations) or dominant (13 populations). Further, the spectrum of the 53 nonsynonymous mutations identified at the sequence level was different between haploids and diploids. These results fit existing theory on the relative abilities of haploids and diploids to adapt and suggest that the ploidy of the fungal pathogen has a strong impact on the evolution of fluconazole resistance.T HE predicted advantages and disadvantages of hapotide site, and their level of dominance can be measured loidy and diploidy, like those of recombination (Kondirectly. drashov 1993), hinge on the ability of populations (a)Two factors are preeminent in determining the effect to cope with deleterious mutation (Kondrashov and of ploidy on the rate of adaptation (Orr and Otto 1994): Crow 1991) and (b) to adapt to new environments (Orr the waiting time for mutations to appear and the fixation and Otto 1994). Our goal in this study was to make a time required for mutations to spread to high frequency direct comparison of ploidy states by measuring the in a population in response to directional selection. Under relative abilities of isogenic haploids and diploids of the conditions of finite population size where the waiting yeast Saccharomyces cerevisiae to adapt to the presence of time for beneficial mutations is the rate-limiting step in the antifungal drug fluconazole (FLC). We followed the adaptation, diploids should, at first glance, have the faster initial, rather than the long-term, responses of haploid rate of adaptation. This is because diploids have twice the and diploid populations to pinpoint the relati...

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Section: Discussionmentioning

confidence: 80%

Haploidy, Diploidy and Evolution of Antifungal Drug Resistance in Saccharomyces cerevisiae

2004

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“…Several of the rearrangements recur in multiple strains. We propose that these rearrangements underlie some of the observed increases in fitness in the evolved strains (1).…”

Section: Discussionmentioning

confidence: 92%

“…Isogenic haploid and diploid clones were propagated asexually for 100-500 generations in glucose-limited continuous culture. Paquin and Adams (1) found that diploids evolve more rapidly than haploids; other research found that usually the ''evolved'' clones assimilate glucose more rapidly than the ancestral strains from which they were derived (3,4). More recently, Ferea et al (5) used DNA microarrays to study genomewide gene expression differences associated with the evolution of one of the Paquin and Adams cultures as well as two others similarly derived by Rosenzweig (5).…”

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confidence: 99%

Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae

Dunham

Badrane

Ferea

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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530

453

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Genome rearrangements, especially amplifications and deletions, have regularly been observed as responses to sustained application of the same strong selective pressure in microbial populations growing in continuous culture. We studied eight strains of budding yeast (Saccharomyces cerevisiae) isolated after 100 -500 generations of growth in glucose-limited chemostats. Changes in DNA copy number were assessed at single-gene resolution by using DNA microarray-based comparative genomic hybridization. Six of these evolved strains were aneuploid as the result of gross chromosomal rearrangements. Most of the aneuploid regions were the result of translocations, including three instances of a shared breakpoint on chromosome 14 immediately adjacent to CIT1, which encodes the citrate synthase that performs a key regulated step in the tricarboxylic acid cycle. Three strains had amplifications in a region of chromosome 4 that includes the high-affinity hexose transporters; one of these also had the aforementioned chromosome 14 break. Three strains had extensive overlapping deletions of the right arm of chromosome 15. Further analysis showed that each of these genome rearrangements was bounded by transposon-related sequences at the breakpoints. The observation of repeated, independent, but nevertheless very similar, chromosomal rearrangements in response to persistent selection of growing cells parallels the genome rearrangements that characteristically accompany tumor progression.

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“…Our theory makes an explicit connection between the shape of the fitness landscape and observable features of adaptation, and it therefore allows us to infer important properties of the fitness landscapes from data. Experimental studies of microbial evolution typically report the mean fitness of the population (21,22) and the mean number of accumulated substitutions (23,24) over time; therefore we develop a theory that predicts these dynamic quantities, which we call the fitness and substitution trajectories, in terms of the underlying fitness landscape.…”

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confidence: 99%

The dynamics of adaptation on correlated fitness landscapes

Kryazhimskiy¹,

Tkačik

Plotkin³

2009

Proc. Natl. Acad. Sci. U.S.A.

120

189

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Evolutionary theory predicts that a population in a new environment will accumulate adaptive substitutions, but precisely how they accumulate is poorly understood. The dynamics of adaptation depend on the underlying fitness landscape. Virtually nothing is known about fitness landscapes in nature, and few methods allow us to infer the landscape from empirical data. With a view toward this inference problem, we have developed a theory that, in the weak-mutation limit, predicts how a population's mean fitness and the number of accumulated substitutions are expected to increase over time, depending on the underlying fitness landscape. We find that fitness and substitution trajectories depend not on the full distribution of fitness effects of available mutations but rather on the expected fixation probability and the expected fitness increment of mutations. We introduce a scheme that classifies landscapes in terms of the qualitative evolutionary dynamics they produce. We show that linear substitution trajectories, long considered the hallmark of neutral evolution, can arise even when mutations are strongly selected. Our results provide a basis for understanding the dynamics of adaptation and for inferring properties of an organism's fitness landscape from temporal data. Applying these methods to data from a long-term experiment, we infer the sign and strength of epistasis among beneficial mutations in the Escherichia coli genome.epistasis | fitness trajectory | substitution trajectory | weak mutation | evolution E volutionary theory predicts that mean fitness will increase over time when a population encounters a new environment. This behavior is observed in natural and laboratory populations. Yet evolutionary theory offers few quantitative predictions for the dynamics of adaptation (1). The primary difficulty is that adaptation depends on the shape of the underlying fitness landscape. Unfortunately, mapping out an organism's fitness landscape is virtually impossible because of its vast dimensionality and the coarse resolution of fitness measurements. Moreover, because of the scarcity of such measurements, most theoretical work has been pursued in isolation from data.Much of the theory of adaptation is concerned with understanding the dynamics on uncorrelated, or "rugged", fitness landscapes. This approach, pioneered by Kingman (2) and Kauffman and Levin (3), has generated many important results (e.g. refs. (4-7)). But many of these results do not extend to landscapes that are correlated. One striking example is the expected length of an adaptive walk: It is extremely short on rugged landscapes (3, 8), but it can be very long on correlated landscapes (9). Although data are scarce, a long-term evolution experiment in Escherichia coli has found that adaptation continues to proceed even after 20,000 generations in a constant environment (10). This observation suggests that fitness landscapes in nature are correlated.A second body of work examines relatively realistic, complex genotype-to-fitness maps-e.g. an RNA folding...

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Frequency of fixation of adaptive mutations is higher in evolving diploid than haploid yeast populations

Cited by 214 publications

References 37 publications

Haploidy, Diploidy and Evolution of Antifungal Drug Resistance in Saccharomyces cerevisiae

Haploidy, Diploidy and Evolution of Antifungal Drug Resistance in Saccharomyces cerevisiae

Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae

The dynamics of adaptation on correlated fitness landscapes

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