Adaptive genome duplication affects patterns of molecular evolution in Saccharomyces cerevisiae

Fisher, Kaitlin J.; Buskirk, Sean W.; Vignogna, Ryan C; Marad, Daniel A.; Lang, Gregory I.

doi:10.1371/journal.pgen.1007396

Cited by 80 publications

(158 citation statements)

References 68 publications

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“…representing a total of 1399 LOH events to construct a LOH map for S. cerevisiae S288c strain (Figure 4). The LOH map validated chromosomal regions with enhanced LOH observed in previous studies -e.g chromosome IV right arm and the rDNA cluster on the right arm of Chromosome XII (Smukowski Heil et al 2017;Fisher et al 2018;James et al 2019). Further, we observe additional LOH hotspots from our map.…”

Section: Mutation Accumulation Lines Of S Cerevisiae Hybrid and Homosupporting

confidence: 88%

Loss of Heterozygosity and Base Mutation Rates Vary AmongSaccharomyces cerevisiaeHybrid Strains

Pankajam¹,

Dash²,

Saifudeen³

et al. 2020

G3 Genes|Genomes|Genetics

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A growing body of evidence suggests that mutation rates exhibit intra-species specific variation. We estimated genome-wide loss of heterozygosity (LOH), gross chromosomal changes, and single nucleotide mutation rates to determine intra-species specific differences in hybrid and homozygous strains of Saccharomyces cerevisiae. The mutation accumulation lines of the S. cerevisiae hybrid backgrounds - S288c/YJM789 (S/Y) and S288c/RM11-1a (S/R) were analyzed along with the homozygous diploids RM11, S288c, and YJM145. LOH was extensive in both S/Y and S/R hybrid backgrounds. The S/Y background also showed longer LOH tracts, gross chromosomal changes, and aneuploidy. Short copy number aberrations were observed in the S/R background. LOH data from the S/Y and S/R hybrids were used to construct a LOH map for S288c to identify hotspots. Further, we observe up to a six-fold difference in single nucleotide mutation rates among the S. cerevisiae S/Y and S/R genetic backgrounds. Our results demonstrate LOH is common during mitotic divisions in S. cerevisiae hybrids and also highlight genome-wide differences in LOH patterns and rates of single nucleotide mutations between commonly used S. cerevisiae hybrid genetic backgrounds.

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Section: Mutation Accumulation Lines Of S Cerevisiae Hybrid and Homosupporting

confidence: 88%

Loss of Heterozygosity and Base Mutation Rates Vary AmongSaccharomyces cerevisiaeHybrid Strains

Pankajam¹,

Dash²,

Saifudeen³

et al. 2020

G3 Genes|Genomes|Genetics

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“…The overwhelming success of polyploids over antimutators during the evolution of pol2-4 msh2Δ cultures supports a model in which they emerge based on their ability to buffer the genome from deleterious mutations, as previously observed with chemically mutagenized haploids [31]. Spontaneous diploids have risen to prominence in previous WT haploid evolution studies over longer time scales [32-34]. The efficiency at which this occurs varies, and may depend on the nature of the strain, the culture conditions, and the presence of preexisting diploids within the initial population.…”

Section: Discussionsupporting

confidence: 59%

“…The efficiency at which this occurs varies, and may depend on the nature of the strain, the culture conditions, and the presence of preexisting diploids within the initial population. Two different studies place the increase in fitness of diploids over WT haploids at around 3.5% per generation [33,34]. With strong mutators, the fitness differential between spontaneous polyploids and haploid cells is likely much larger and constantly increasing as mutations accumulate within haploid genomes.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous polyploids and antimutators compete during the evolution of mutator cells

Tracy

Lee

Hearn

et al. 2019

Preprint

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26DNA polymerase (Pol) proofreading and mismatch repair (MMR) defects produce 27 "mutator" phenotypes capable of driving tumorigenesis. "Ultra-mutated" cancers with defects in 28 both pathways exhibit an explosive increase in point mutation burden that appears to reach an 29 upper limit of ~250 mutations/Mb, which may be evidence for negative selection. Simultaneous 30 defects in proofreading and MMR drive error-induced extinction (EEX) of haploid yeast. Some 31 yeast mutants escape extinction through antimutator mutations that suppress the mutator 32 phenotype. We report here that other yeast mutants escape by spontaneous polyploidization. 33 We sought to compare these two adaptive strategies during the evolution of haploid and diploid 34 mutators. We first evolved 89 independently isolated haploid mutator strains with mutation rates 35 an order of magnitude below the lethal threshold. Polyploid cells overtook nearly every culture.36 In a similar manner, we evolved strong diploid mutators, but found only a single tetraploid 37 emerged after ~250 cellular generations. Antimutators dominated these late passage cultures 38 and were present after only 30-40 cellular generations. Whole genome sequencing of 39 independent isolates from the same culture allowed us to construct phylogenetic trees that 40 revealed that a single subclone swept through each culture carrying multiple antimutator 41 mutations affecting the mutator polymerase. Variation in mutation rate between subclones from 42 the same culture suggests some strains carry additional antimutator alleles in other genes. Our 43 findings in diploid mutator yeast suggest that mutator-driven cancer cells may also adapt to the 44 threat of extinction by accumulating multiple antimutator alleles that cooperatively reduce 45 mutation rate to tolerable levels. 46Author summary 47 "Mutator" tumor cells that cannot correct DNA replication errors exhibit an extremely high 48 mutation rate that accelerates their evolution. But this gamble puts them at risk for extinction 3 49 due to the accumulation of harmful mutations. Mutator yeast cells escape extinction through 50 "antimutator" mutations that lower mutation rate. We discovered that yeast cells also adapt by 51 duplicating their genome. To understand which adaptation may emerge in mutator-driven 52 tumors, we evolved haploid and diploid mutator yeast cells by long-term propagation. Haploid 53 mutators primarily adapted by genome duplication, thereby protecting themselves from 54 recessive lethal mutations. In contrast, diploid mutators evolved by acquiring multiple 55 antimutator mutations. Our results suggest that mutator-driven tumors may similarly accumulate 56 combinations of mutations that attenuate their high mutation rates.4 57 58The high fidelity of DNA replication and repair prevents mutations that might otherwise 59 lead to cancer. As first proposed more than 40 years ago, cells with defects in these pathways 60 exhibit an elevated mutation rate ("mutator phenotype") and an accelerated path to malignancy 61...

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“…Further evidence comes from experimental case studies observing that under relaxed selection, diploid S. cerevisiae populations gained significantly more chromosomes than haploid populations (binomial test: p < 10 −10 ; Sharp, Sandell, James, & Otto, ). Another study, which compared haploids with populations that had undergone whole genome duplication (WGD) to become diploid, found aneuploidy exclusively in the diploid populations (Fisher, Buskirk, Vignogna, Marad, & Lang, ). A further study found that haploid and diploid strains were significantly less likely to contain aneuploid chromosomes than >3N populations (Fisher's exact test p < .001; n of strains = 142, (Zhu et al, ).…”

Section: Patterns Of Aneuploidy—chromosome Size Ploidy and The Envimentioning

confidence: 99%

Aneuploidy in yeast: Segregation error or adaptation mechanism?

Gilchrist

Stelkens

2019

Yeast

104

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Aneuploidy is the loss or gain of chromosomes within a genome. It is often detrimental and has been associated with cell death and genetic disorders. However, aneuploidy can also be beneficial and provide a quick solution through changes in gene dosage when cells face environmental stress. Here, we review the prevalence of aneuploidy in Saccharomyces, Candida, and Cryptococcus yeasts (and their hybrid offspring) and analyse associations with chromosome size and specific stressors. We discuss how aneuploidy, a segregation error, may in fact provide a natural route for the diversification of microbes and enable important evolutionary innovations given the right ecological circumstances, such as the colonisation of new environments or the transition from commensal to pathogenic lifestyle. We also draw attention to a largely unstudied cross link between hybridisation and aneuploidy. Hybrid meiosis, involving two divergent genomes, can lead to drastically increased rates of aneuploidy in the offspring due to antirecombination and chromosomal missegregation. Because hybridisation and aneuploidy have both been shown to increase with environmental stress, we believe it important and timely to start exploring the evolutionary significance of their co‐occurrence.

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Adaptive genome duplication affects patterns of molecular evolution in Saccharomyces cerevisiae

Cited by 80 publications

References 68 publications

Loss of Heterozygosity and Base Mutation Rates Vary AmongSaccharomyces cerevisiaeHybrid Strains

Loss of Heterozygosity and Base Mutation Rates Vary AmongSaccharomyces cerevisiaeHybrid Strains

Spontaneous polyploids and antimutators compete during the evolution of mutator cells

Aneuploidy in yeast: Segregation error or adaptation mechanism?

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