Ty elements are involved in the formation of deletions in DEL1 strains of saccharomyces cerevisiae

Liebman, Susan W.; Shalit, P; Picologlou, Susan

doi:10.1016/0092-8674(81)90209-9

Cited by 53 publications

(27 citation statements)

References 27 publications

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“…Ectopic recombination events involving Tys have been noted before in closely related yeast species (9), lab strains (38), and industrial strains (39), and their occurrence has been studied extensively by a number of groups (40)(41)(42). Cha and Kleckner (43) recently provided a potential mechanistic reason that transposon sequences are so strongly correlated with chromosome breakpoints.…”

Section: Discussionmentioning

confidence: 99%

Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae

Dunham

Badrane

Ferea

et al. 2002

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

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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Section: Discussionmentioning

confidence: 99%

Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae

Dunham

Badrane

Ferea

et al. 2002

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

530

453

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“…Although deletions of CYC1 are observed at very low frequency in most wild-type strains, Liebman and colleagues (Liebman et al 1979) found a strain in which deletions of three linked genes (one of which was CYC1) occurred at a relatively high rate (10 25 -10 26 events/ division). Subsequently, it was shown that in strains that had a high deletion rate, the CYC1 gene was flanked by two 6-kb Ty retrotransposons in direct orientation and that the deletion events were a consequence of homologous recombination between the Ty elements (Liebman et al 1981). Similarly, recombination between flanking delta LTR elements (the long-terminal-repeat sequences associated with Ty1 and Ty2 elements) was implicated in the high frequency of deletions at the SUP4 locus (Rothstein et al 1987).…”

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Gene Copy-Number Variation in Haploid and Diploid Strains of the Yeast Saccharomyces cerevisiae

et al. 2013

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The increasing ability to sequence and compare multiple individual genomes within a species has highlighted the fact that copy-number variation (CNV) is a substantial and underappreciated source of genetic diversity. Chromosome-scale mutations occur at rates orders of magnitude higher than base substitutions, yet our understanding of the mechanisms leading to CNVs has been lagging. We examined CNV in a region of chromosome 5 (chr5) in haploid and diploid strains of Saccharomyces cerevisiae. We optimized a CNV detection assay based on a reporter cassette containing the SFA1 and CUP1 genes that confer gene dosage-dependent tolerance to formaldehyde and copper, respectively. This optimized reporter allowed the selection of low-order gene amplification events, going from one copy to two copies in haploids and from two to three copies in diploids. In haploid strains, most events involved tandem segmental duplications mediated by nonallelic homologous recombination between flanking direct repeats, primarily Ty1 elements. In diploids, most events involved the formation of a recurrent nonreciprocal translocation between a chr5 Ty1 element and another Ty1 repeat on chr13. In addition to amplification events, a subset of clones displaying elevated resistance to formaldehyde had point mutations within the SFA1 coding sequence. These mutations were all dominant and are proposed to result in hyperactive forms of the formaldehyde dehydrogenase enzyme.A S a consequence of studies that utilize genomic microarrays and next-generation DNA sequencing, it has become clear that much of the natural genetic variation that exists between individuals is due to alterations in the number of copies of genes rather than differences in the nucleotide sequence (Girirajan et al. 2011;Veltman and Brunner 2012). It has been calculated that 8-25 kb of DNA are deleted or duplicated per generation in humans compared to about 100 bp of point mutations (Itsara et al. 2010). Although deletions and duplications vary in size from a few base pairs (for example, changes in the lengths of microsatellites) to many megabases (for example, changes in ploidy), Girirajan et al. (2011) define copy-number variants (CNVs) in humans as changes that vary in size between 50 bp and 1 Mb. While most CNV events have no obvious effect, a significant number are associated with human diseases including Charcot-Marie-Tooth syndrome, autosomal dominant leukodystrophy, Williams syndrome, several cancer predispositions, and autism-related and other neurodevelopmental disorders (Abrahams and Geschwind 2008;Girirajan et al. 2011;Krepischi et al. 2012;Malhotra and Sebat 2012;Sullivan et al. 2012). There is also strong evidence suggesting that CNVs played a significant role in human evolution (Iskow et al. 2012). Finally, multiple somatic CNV events are frequently observed in the altered karyotypes of cancer cells (Stratton et al. 2009).CNVs have also been widely observed in natural populations and have been studied in detail in model organisms. In the discussion below, w...

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“…In the yeast Saccharomyces cerevisiae, Ty retrotransposons have been shown to play a significant role in mediating genomic rearrangements, including gene amplifications (see Mieczkowski et al 2006 for a review). These changes have been shown to occur under many different growth conditions, including selections for increased gene expression or drug resistance, after stress, or spontaneously (for examples, see Liebman et al 1981;Brown et al 1998;Rachidi et al 1999;Hughes et al 2000;Dunham et al 2002;Koszul et al 2004;Schacherer et al 2004;Selmecki et al 2006;Argueso et al 2008). A recent study showed that Tymediated amplifications are a common occurrence when S. cerevisiae is grown under conditions limiting for glucose, phosphate, or sulfate (Gresham et al 2008).…”

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confidence: 99%

Alterations in DNA Replication and Histone Levels Promote Histone Gene Amplification in Saccharomyces cerevisiae

Libuda¹,

Winston

2010

Genetics

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Gene amplification, a process that increases the copy number of a gene or a genomic region to two or more, is utilized by many organisms in response to environmental stress or decreased levels of a gene product. Our previous studies in Saccharomyces cerevisiae identified the amplification of a histone H2A-H2B gene pair, HTA2-HTB2, in response to the deletion of the other H2A-H2B gene pair, HTA1-HTB1. This amplification arises from a recombination event between two flanking Ty1 elements to form a new, stable circular chromosome and occurs at a frequency higher than has been observed for other Ty1-Ty1 recombination events. To understand the regulation of this amplification event, we screened the S. cerevisiae nonessential deletion set for mutations that alter the amplification frequency. Among the deletions that increase HTA2-HTB2 amplification frequency, we identified those that either decrease DNA replication fork progression (rrm3D, dpb3D, dpb4D, and clb5D) or that reduce histone H3-H4 levels (hht2-hhf2D). These two classes are related because reduced histone H3-H4 levels increase replication fork pauses, and impaired replication forks cause a reduction in histone levels. Consistent with our mutant screen, we found that the introduction of DNA replication stress by hydroxyurea induces the HTA2-HTB2 amplification event. Taken together, our results suggest that either reduced histone levels or slowed replication forks stimulate the HTA2-HTB2 amplification event, contributing to the restoration of normal chromatin structure.

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Ty elements are involved in the formation of deletions in DEL1 strains of saccharomyces cerevisiae

Cited by 53 publications

References 27 publications

Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae

Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae

Gene Copy-Number Variation in Haploid and Diploid Strains of the Yeast Saccharomyces cerevisiae

Alterations in DNA Replication and Histone Levels Promote Histone Gene Amplification in Saccharomyces cerevisiae

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