A Fine-Structure Map of Spontaneous Mitotic Crossovers in the Yeast Saccharomyces cerevisiae

Lee, Phoebe S.; Greenwell, Patricia W.; Dominska, Margaret; Gawel, Malgorzata; Hamilton, Monica L.; Petes, Thomas D.

doi:10.1371/journal.pgen.1000410

Cited by 106 publications

(252 citation statements)

References 65 publications

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“…Large-scale LOH is thought to primarily result from mitotic recombination initiated by double-stranded breaks during replication (20). Meiotic recombination can also lead to LOH but the size of such regions is generally smaller and they are more uniformly distributed across chromosomes (21).…”

Section: Resultsmentioning

confidence: 99%

Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae

Magwene

Kayıkçı

Granek

et al. 2011

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

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We carried out a population genomic survey of Saccharomyces cerevisiae diploid isolates and find that many budding yeast strains have high levels of genomic heterozygosity, much of which is likely due to outcrossing. We demonstrate that variation in heterozygosity among strains is correlated with a life-history tradeoff that involves how readily yeast switch from asexual to sexual reproduction under nutrient stress. This trade-off is reflected in a negative relationship between sporulation efficiency and pseudohyphal development and correlates with variation in the expression of RME1, a transcription factor with pleiotropic effects on meiosis and filamentous growth. Selection for alternate lifehistory strategies in natural versus human-associated environments likely contributes to differential maintenance of genomic heterozygosity through its effect on the frequency that yeast lineages experience sexual cycles and hence the opportunity for inbreeding. In addition to elevated levels of heterozygosity, many strains exhibit large genomic regions of loss-of-heterozygosity (LOH), suggesting that mitotic recombination has a significant impact on genetic variation in this species. This study provides new insights into the roles that both outcrossing and mitotic recombination play in shaping the genome architecture of Saccharomyces cerevisiae. This study also provides a unique case where stark differences in the genomic distribution of genetic variation among individuals of the same species can be largely explained by a lifehistory trade-off.T he frequency of sex and the nature of breeding systems have a profound effect on genome variation and evolution. For example, inbred populations have an increased frequency of homozygous genotypes (1), lower effective rates of recombination (2), and smaller effective population sizes relative to outcrossed populations with the same number of individuals (3). Likewise, clonal populations are expected to exhibit high levels of heterozygosity coupled with increased allelic diversity but decreased genotypic diversity relative to sexual populations (4).The budding yeast Saccharomyces cerevisiae is one of the best studied model organisms, but relatively little is known about the importance of sexual versus asexual reproduction and inbreeding versus outcrossing in shaping genome evolution in this species. One recent study estimated that outcrossing occurs approximately once every 50,000 generations in S. cerevisiae (5), but low rates of outcrossing do not preclude the possibility that outcrossing has an important impact on genetic variation. Studies of the closely related yeast Saccharomyces paradoxus suggest that sexual cycles are rare relative to asexual cycles and that when sex does occur it primarily involves inbreeding (6, 7). However, S. paradoxus exhibits distinctly different intra-and interpopulation patterns of variation than does S. cerevisiae (8), and hence these findings may not be generalizable across the Saccharomyces genus.Patterns of heterozygosity are an important indica...

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Section: Resultsmentioning

confidence: 99%

Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae

Magwene

Kayıkçı

Granek

et al. 2011

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

160

179

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“…2A). SLA11.7, constructed by mating two sequence-diverged haploid strains (W303a and YJM789), is heterozygous for approximately 55,000 SNPs (14). Mitotic crossovers result in LOH of markers that are centromere-distal to the exchange ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The relevant features of the PG311 diploid genotype are shown in Fig. 1, and the construction of PG311 has been described previously (14). SLA11.7 is an isogenic derivative of PG311 in which the V261553::LEU2 insertion is replaced by V261553::KANMX by standard procedures.…”

Section: Methodsmentioning

confidence: 99%

“…We identified Can R red/white-sectored colonies using the medium and experimental conditions described previously (14). Sectors were screened for RUD events on standard rich growth medium plates containing 200 μg/mL of hygromycin or 300 μg/mL of geneticin.…”

Section: Methodsmentioning

confidence: 99%

“…For the other strains, LOH was assessed using an SNP located near the right end of chromosome V. The YJM789-derived and W303a-derived haploids differ at Saccharomyces Genome Database (SGD) coordinates 560715 and 560716, resulting in an EcoRI site at this position in YJM789 that is absent in W303a. We can detect LOH by PCR amplification of the region flanking the site, followed by treatment with EcoRI and gel electrophoretic analysis of the resulting fragments (14). The following primers were used for this analysis: 5′-TTCTCAGCCGTA-CAATCATGC and 5′-AAACTCCTTCCAAAGGGTCTGG.…”

Section: Methodsmentioning

confidence: 99%

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Reciprocal uniparental disomy in yeast

Andersen

Petes

2012

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

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In the diploid cells of most organisms, including humans, each chromosome is usually distinguishable from its partner homolog by multiple single-nucleotide polymorphisms. One common type of genetic alteration observed in tumor cells is uniparental disomy (UPD), in which a pair of homologous chromosomes are derived from a single parent, resulting in loss of heterozygosity for all single-nucleotide polymorphisms while maintaining diploidy. Somatic UPD events are usually explained as reflecting two consecutive nondisjunction events. Here we report a previously undescribed mode of chromosome segregation in Saccharomyces cerevisiae in which one cell division produces daughter cells with reciprocal UPD for the same pair of chromosomes without an aneuploid intermediate. One pair of sister chromatids is segregated into one daughter cell and the other pair is segregated into the other daughter cell, mimicking a meiotic chromosome segregation pattern. We term this process “reciprocal uniparental disomy.”

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Identification of recurrent type-2NF1microdeletions reveals a mitotic nonallelic homologous recombination hotspot underlying a human genomic disorder

et al. 2012

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Nonallelic homologous recombination (NAHR) is one of the major mechanisms underlying copy number variation in the human genome. Although several disease-associated meiotic NAHR breakpoints have been analyzed in great detail, hotspots for mitotic NAHR are not well characterized. Type-2 NF1 microdeletions, which are predominantly of postzygotic origin, constitute a highly informative model with which to investigate the features of mitotic NAHR. Here, a custom-designed MLPA- and PCR-based approach was used to identify 23 novel NAHR-mediated type-2 NF1 deletions. Breakpoint analysis of these 23 type-2 deletions, together with 17 NAHR-mediated type-2 deletions identified previously, revealed that the breakpoints are nonuniformly distributed within the paralogous SUZ12 and SUZ12P sequences. Further, the analysis of this large group of type-2 deletions revealed breakpoint recurrence within short segments (ranging in size from 57 to 253-bp) as well as the existence of a novel NAHR hotspot of 1.9-kb (termed PRS4). This hotspot harbored 20% (8/40) of the type-2 deletion breakpoints and contains the 253-bp recurrent breakpoint region BR6 in which four independent type-2 deletion breakpoints were identified. Our findings indicate that a combination of an open chromatin conformation and short non-B DNA-forming repeats may predispose to recurrent mitotic NAHR events between SUZ12 and its pseudogene.

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A Fine-Structure Map of Spontaneous Mitotic Crossovers in the Yeast Saccharomyces cerevisiae

Cited by 106 publications

References 65 publications

Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae

Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae

Reciprocal uniparental disomy in yeast

Identification of recurrent type-2NF1microdeletions reveals a mitotic nonallelic homologous recombination hotspot underlying a human genomic disorder

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