The origins of replication of the yeast mitochondrial genome and the phenomenon of suppressivity

Zamaroczy, Miklos de; Marotta, Renzo; Faugeron-Fonty, Godeleine; Goursot, Regina; Mangin, Marguerite; Baldacci, Giuseppe; Bernardi, Giorgio

doi:10.1038/292075a0

Cited by 140 publications

(106 citation statements)

References 35 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…The preferred sites for DNA double-strand breaks, which initiate recombination, involve two Ty elements that are in close proximity and have the potential to form a hairpin-like secondary structure (Lemoine et al 2005). The mitochondrial genome of S. cerevisiae contains several putative origin-of-replication (ori) sequences that could also form hairpin-like secondary structures (de Zamaroczy et al 1981). By analogy to Ty-mediated recombination, we propose that the MIP1-661A allele reduces the abundance of the Mip1 protein, leads to slowmoving replication forks, or gives rise to other perturbations in mtDNA replication that expose the ori sequences as fragile sites of double-strand DNA.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains

et al. 2009

View full text Add to dashboard Cite

The mitochondrial genome (mtDNA) is required for normal cellular function; inherited and somatic mutations in mtDNA lead to a variety of diseases. Saccharomyces cerevisiae has served as a model to study mtDNA integrity, in part because it can survive without mtDNA. A measure of defective mtDNA in S. cerevisiae is the formation of petite colonies. The frequency at which spontaneous petite colonies arise varies by $100-fold between laboratory and natural isolate strains. To determine the genetic basis of this difference, we applied quantitative trait locus (QTL) mapping to two strains at the opposite extremes of the phenotypic spectrum: the widely studied laboratory strain S288C and the vineyard isolate RM11-1a. Four main genetic determinants explained the phenotypic difference. Alleles of SAL1, CAT5, and MIP1 contributed to the high petite frequency of S288C and its derivatives by increasing the formation of petite colonies. By contrast, the S288C allele of MKT1 reduced the formation of petite colonies and compromised the growth of petite cells. The former three alleles were found in the EM93 strain, the founder that contributed $88% of the S288C genome. Nearly all of the phenotypic difference between S288C and RM11-1a was reconstituted by introducing the common alleles of these four genes into the S288C background. In addition to the nuclear gene contribution, the source of the mtDNA influenced its stability. These results demonstrate that a few rare genetic variants with individually small effects can have a profound phenotypic effect in combination. Moreover, the polymorphisms identified in this study open new lines of investigation into mtDNA maintenance.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The majority of spontaneously arising petite cells are rho À (de Zamaroczy et al 1981). Analysis of the mtDNA in a number of spontaneous petite mutants suggests that most such rho À genomes are a head-to-tail tandem repetition of a segment of the rho 1 mtDNA (FaugeronFonty et al 1979).…”

mentioning

confidence: 99%

Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains

et al. 2009

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

“…, almost all progeny are respiration defective (7,12). HS [rho Ϫ ] mtDNA is a tandem array of a small region (1 kb or less) of mtDNA that has one of the several replication origins of [rho ϩ ] mtDNA (70 to 85 kbp) (7,12). HS [rho Ϫ ] mtDNA has a higher density of replication origins than [rho ϩ ] mtDNA, and this suggests that a replication advantage of HS [rho Ϫ ] mtDNA over [rho ϩ ] mtDNA results in hypersuppressiveness.…”

mentioning

confidence: 99%

DNA Recombination-Initiation Plays a Role in the Extremely Biased Inheritance of Yeast [rho⁻] Mitochondrial DNA That Contains the Replication Origin ori5

Ling

Hori

Shibata

2007

Molecular and Cellular Biology

111

View full text Add to dashboard Cite

Hypersuppressiveness, as observed inEukaryotic cells gain most of the energy required for cellular functions by oxidative respiration in mitochondria. These organelles contain hundreds to thousands of copies of a mitochondrial DNA (mtDNA) genome that encodes components essential for respiration and protein synthesis. Generally, mitochondrial alleles segregate during vegetative cell growth (vegetative segregation), and all copies of mtDNA within a cell or an individual generally have the same sequence (homoplasmy). In patients with mitochondrial myopathies, the progressive accumulation of mtDNA with large deletions leads to a heteroplasmic state in specific tissues (20; for review, see references 43 and 54). This phenomenon may be caused by the selective replication and/or segregation of mtDNA bearing the deletion; however, genetic analysis of mtDNA processes in mammals has been hampered by the strict maternal inheritance of mitochondria. The yeast Saccharomyces cerevisiae is a suitable model system because of its biparental mtDNA inheritance (14).The extremely biased inheritance of mtDNA with a large deletion is known in S. cerevisiae as "hypersuppressiveness. Two mechanisms for the initiation of mtDNA replication in yeast have been proposed: mitochondrial transcriptional RNA polymerase (Rpo41)-primed initiation and recombination-mediated initiation. Rpo41-primed DNA replication is similar to that observed in mammalian mitochondria. In support of this mechanism, each mtDNA replication origin shares sequence similarity with the heavy-strand replication origin of mammalian mtDNA, including the presence of a transcription promoter and three GC-rich clusters (2, 13). RNA synthesized by Rpo41 from mtDNA replication-origin promoters has been detected, and an endoribonuclease that cleaves the synthesized RNA at sites that correspond to regions of transition from RNA to DNA synthesis has been detected (3,49,53). The intact replication-origin promoter is required for hypersuppressiveness (36). However, this transcription-dependent process is not the sole mechanism for the initiation of mtDNA replication, since both the replication origin and RPO41 are dispensable for the maintenance of [rho Ϫ ] mtDNA (18,53). In addition, it has been reported that the selective inheritance of hypersuppressive [rho Ϫ ] mtDNA relative to nonhypersuppres-* Corresponding author. Mailing address:

show abstract

“…The remaining fragment becomes tandemly repeated to yield a final chromosome size near the wild-type 80 kb. Because the repeat unit typically contains an origin of replication, it has been hypothesized that such genomes may enjoy a replication advantage over wild-type mtDNA (15,17). Yeast cells homoplasmic for such mtDNA deletions show the petite phenotype, which is diagnosed by the inability to grow on carbon sources such as glycerol that require respiration, and by the formation of smaller colonies on fermentable carbon sources such as dextrose.…”

mentioning

confidence: 99%

Conflicting levels of selection in the accumulation of mitochondrial defects in Saccharomyces cerevisiae

Taylor

Zeyl

Cooke

2002

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

115

View full text Add to dashboard Cite

The somatic accumulation of defective mitochondria causes human degenerative syndromes, senescence in fungi, and male sterility in plants. These diverse phenomena may result from conflicts between natural selection at different levels of organization. Such conflicts are fundamental to the evolution of cooperating groups, from cells to populations. We present a model in which defective mitochondrial genomes accumulate because of a within-cell replication advantage when among-cell selection for efficient respiration is relaxed. We tested the model by using experimental populations of the yeast Saccharomyces cerevisiae. We constructed yeast strains that were heteroplasmic for mitochondrial mutations that destroy the ability to respire (the petite phenotype) and followed the accumulation of mitochondrial defects in cultures with different effective population sizes. As predicted by the model, the inability to respire evolved only in small populations of S. cerevisiae, where among-cell selection favoring cells that can respire was reduced relative to within-cell selection favoring parasitic mitochondria. In a control experiment, mitochondrial point mutations that confer resistance to chloramphenicol showed no tendency to change in frequency under any culture conditions. The accumulation of some mitochondrial defects is therefore an evolutionary process, involving multiple levels of selection. The relative intensities of within-and among-cell selection may also explain the tissue specificity of human mitochondrial defects.

show abstract

The origins of replication of the yeast mitochondrial genome and the phenomenon of suppressivity

Cited by 140 publications

References 35 publications

Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains

Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains

DNA Recombination-Initiation Plays a Role in the Extremely Biased Inheritance of Yeast [rho⁻] Mitochondrial DNA That Contains the Replication Origin ori5

Conflicting levels of selection in the accumulation of mitochondrial defects in Saccharomyces cerevisiae

Contact Info

Product

Resources

About

The origins of replication of the yeast mitochondrial genome and the phenomenon of suppressivity

Cited by 140 publications

References 35 publications

Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains

Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains

DNA Recombination-Initiation Plays a Role in the Extremely Biased Inheritance of Yeast [rho−] Mitochondrial DNA That Contains the Replication Origin ori5

Conflicting levels of selection in the accumulation of mitochondrial defects in Saccharomyces cerevisiae

Contact Info

Product

Resources

About

DNA Recombination-Initiation Plays a Role in the Extremely Biased Inheritance of Yeast [rho⁻] Mitochondrial DNA That Contains the Replication Origin ori5