Unequal crossing over in the ribosomal DNA of Saccharomyces cerevisiae

Szostak, Jack W.; Wü, Ray

doi:10.1038/284426a0

Cited by 408 publications

(239 citation statements)

References 37 publications

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“…Extending these analyses to more and varied species will help clarify this. Our results also provide critical data for the formulation of theoretical models of concerted evolution, as now both the rate of rDNA recombination (e.g., Szostak and Wu 1980;Gangloff et al 1996) and the level of rDNA array heterogeneity are known. Finally, although our results seem to justify the decision of some genome projects not to sequence long repeat arrays such as the rDNA, such data are useful and can help us decipher the evolutionary dynamics of these intriguing regions of the genome.…”

Section: Discussionmentioning

confidence: 99%

“…This unusual mode of evolution, where repeats within a genome are more similar to each other than they are to "orthologous" repeats in a related species, is defined as concerted evolution (Zimmer et al 1980). The molecular process responsible for concerted evolution is known as homogenization (Dover 1982), and although not fully elucidated, is thought to involve continual turnover of repeat copies by unequal recombination (e.g., Smith 1973;Szostak and Wu 1980;Kobayashi et al 1998). However, recent studies have shown that several repeat families previously thought to evolve by concerted evolution actually evolve via a different evolutionary process known as birth-and-death evolution (e.g., Nei et al 1997Nei et al , 2000Rooney and Ward 2005).…”

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confidence: 99%

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Highly efficient concerted evolution in the ribosomal DNA repeats: Total rDNA repeat variation revealed by whole-genome shotgun sequence data

Ganley¹,

Kobayashi²

2007

Genome Res.

329

268

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Repeat families within genomes are often maintained with similar sequences. Traditionally, this has been explained by concerted evolution, where repeats in an array evolve "in concert" with the same sequence via continual turnover of repeats by recombination. Another form of evolution, birth-and-death evolution, can also explain this pattern, although in this case selection is the critical force maintaining the repeats. The level of intragenomic variation is the key difference between these two forms of evolution. The prohibitive size and repetitive nature of large repeat arrays have made determination of the absolute level of intragenomic repeat variability difficult, thus there is little evidence to support concerted evolution over birth-and-death evolution for many large repeat arrays. Here we use whole-genome shotgun sequence data from the genome projects of five fungal species to reveal absolute levels of sequence variation within the ribosomal RNA gene repeats (rDNA). The level of sequence variation is remarkably low. Furthermore, the polymorphisms that are detected are not functionally constrained and seem to exist beneath the level of selection. These results suggest the rDNA is evolving via concerted evolution. Comparisons with a repeat array undergoing birth-and-death evolution provide a clear contrast in the level of repeat array variation between these two forms of evolution, confirming that the rDNA indeed does evolve via concerted evolution. These low levels of intra-genomic variation are consistent with a model of concerted evolution in which homogenization is very rapid and efficiently maintains highly similar repeat arrays.[Supplemental material is available online at www.genome.org.]Repetitive elements are an abundant feature of genomes (Britten and Kohne 1968) and play critical roles in cell biology, genome structure, and adaptive evolution (Andersson et al. 1998;Shapiro and von Sternberg 2005). In many cases, repeats from a repeat family are highly similar to one another within a genome, a pattern that persists through evolutionary time even though sequence differences are apparent between species (Brown et al. 1972). Thus, the repeats seem to be maintained as a coherent family. This pattern is contrary to the expectations of conventional evolution, where repeats are expected to evolve independently ( Fig. 1) and diverge with time. This unusual mode of evolution, where repeats within a genome are more similar to each other than they are to "orthologous" repeats in a related species, is defined as concerted evolution (Zimmer et al. 1980). The molecular process responsible for concerted evolution is known as homogenization (Dover 1982), and although not fully elucidated, is thought to involve continual turnover of repeat copies by unequal recombination (e.g., Smith 1973;Szostak and Wu 1980;Kobayashi et al. 1998). However, recent studies have shown that several repeat families previously thought to evolve by concerted evolution actually evolve via a different evolutionary process known as birth-...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Highly efficient concerted evolution in the ribosomal DNA repeats: Total rDNA repeat variation revealed by whole-genome shotgun sequence data

Ganley¹,

Kobayashi²

2007

Genome Res.

329

268

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“…These events have been observed when breaks occur in regions containing tandem repeats. The recombinants show a variable number of repeats, a phenomenon known as unequal sister-chromatid exchange 44,45 . One way to explain this is if the end of the broken chromosome anneals to a different repeat in the sister chromatid resulting in either loss or gain of one or more repeats 11 .…”

Section: Consequence Of Mutagenic Repair Of Double-strand Breaksmentioning

confidence: 99%

Links between replication, recombination and genome instability in eukaryotes

Flores‐Rozas

Kolodner

2000

Trends in Biochemical Sciences

107

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Double-strand breaks in DNA can be repaired by homologous recombination including breakinduced replication. In this reaction, the end of a broken DNA invades an intact chromosome and primes DNA replication resulting in the synthesis of an intact chromosome. Break-induced replication has also been suggested to cause different types of genome rearrangements.The ability of cells to repair double-strand breaks (DSBs) is critical for cell viability. Failure to correct such damage can result in cell cycle arrest, cell death and, if repaired incorrectly, the loss of genetic information or the accumulation of mutations. DSBs can arise in cells by exposure to ionizing radiation 1 and other types of DNA-damaging agents or through mechanical stress. In addition, some cellular processes, like DNA replication, can generate DSBs. These could arise by the action of nucleases at unprotected sites where replication forks stall, as a consequence of DNA polymerases (Pols) replicating across nicked chromosomes, as well as by the active processing of stalled replication forks by specific enzyme systems [2][3][4] . DSBs can also occur naturally and play important roles in processes such as meiosis 5 , mating-type switching 6 and mammalian V(D)J recombination 7 .Cells have developed a number of mechanisms to repair such lesions. In Saccharomyces cerevisiae, most of the repair of DSBs is carried out by mechanisms that promote homologous recombination. This requires the existence in the cell of sequences that are homologous to those affected by the DSB. Non-homologous end-joining also rejoins DSBs in S. cerevisiae albeit less efficiently than homologous recombination; non-homologous endjoining appears to be of greater importance in mammalian cells 8 . General models of recombinationSeveral recent reviews have discussed recombination and the repair of DSBs in detail 4,9-14 . Given the increasing evidence that translocations and other types of genome rearrangements arise from inappropriate repair of DSBs, we will focus on the repair of DSBs by a homologous recombination pathway that involves extensive DNA synthesis. Such a process, termed break-induced replication (BIR), has been suggested based on the observations by 16 . In this study, activation of the transcription enhancer element HOT1 creates a recombination hotspot suggested to act by generating DSBs that are processed resulting in strains with distal markers converted to those present in the homologous chromosome. The resulting gene conversion, which could extend over regions as long as 75 kb, was proposed to arise by replication of a primer structure generated by the centromere-containing fragment invading the homologous chromosome in a process analogous to that described for bacteriophage T4 (Ref. 17 (Fig. 1a). In both cases the ends of the broken DNA molecule are degraded by exonucleases creating 3′ overhangs that invade the homologous template. The result is the formation of a D-loop in which the annealed invading end serves as a primer that is extended by the DNA syn...

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“…Frequent recombination events are required to maintain rDNA homogeneity (15,16) and result in the loss of markers integrated in the rDNA (7). However, this HR-dependent pathway regulated by Sir2 is nondirectional; repeat gain and loss occurs at equivalent rates, so no change in average copy number is observed over time (13).…”

mentioning

confidence: 99%

Regulation of ribosomal DNA amplification by the TOR pathway

Jack

Cruz

Hull

et al. 2015

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

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Repeated regions are widespread in eukaryotic genomes, and key functional elements such as the ribosomal DNA tend to be formed of high copy repeated sequences organized in tandem arrays. In general, high copy repeats are remarkably stable, but a number of organisms display rapid ribosomal DNA amplification at specific times or under specific conditions. Here we demonstrate that target of rapamycin (TOR) signaling stimulates ribosomal DNA amplification in budding yeast, linking external nutrient availability to ribosomal DNA copy number. We show that ribosomal DNA amplification is regulated by three histone deacetylases: Sir2, Hst3, and Hst4. These enzymes control homologous recombination-dependent and nonhomologous recombination-dependent amplification pathways that act in concert to mediate rapid, directional ribosomal DNA copy number change. Amplification is completely repressed by rapamycin, an inhibitor of the nutrientresponsive TOR pathway; this effect is separable from growth rate and is mediated directly through Sir2, Hst3, and Hst4. Caloric restriction is known to up-regulate expression of nicotinamidase Pnc1, an enzyme that enhances Sir2, Hst3, and Hst4 activity. In contrast, normal glucose concentrations stretch the ribosome synthesis capacity of cells with low ribosomal DNA copy number, and we find that these cells show a previously unrecognized transcriptional response to caloric excess by reducing PNC1 expression. PNC1 down-regulation forms a key element in the control of ribosomal DNA amplification as overexpression of PNC1 substantially reduces ribosomal DNA amplification rate. Our results reveal how a signaling pathway can orchestrate specific genome changes and demonstrate that the copy number of repetitive DNA can be altered to suit environmental conditions. ribosomal DNA | homologous recombination | Sir2 | copy number variation | TOR

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Unequal crossing over in the ribosomal DNA of Saccharomyces cerevisiae

Cited by 408 publications

References 37 publications

Highly efficient concerted evolution in the ribosomal DNA repeats: Total rDNA repeat variation revealed by whole-genome shotgun sequence data

Highly efficient concerted evolution in the ribosomal DNA repeats: Total rDNA repeat variation revealed by whole-genome shotgun sequence data

Links between replication, recombination and genome instability in eukaryotes

Regulation of ribosomal DNA amplification by the TOR pathway

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