Cited by 77Fungal and yeast genetics researchDNA Repair MechanismsMitochondrial Function and Pathology

A Genome-Wide Map of Mitochondrial DNA Recombination in Yeast

Open access
Fritsch, Emilie S, Chabbert, Christophe D, Klaus, Bernd, Steinmetz, Lars M·2014·Genetics

Abstract

In eukaryotic cells, the production of cellular energy requires close interplay between nuclear and mitochondrial genomes. The mitochondrial genome is essential in that it encodes several genes involved in oxidative phosphorylation. Each cell contains several mitochondrial genome copies and mitochondrial DNA recombination is a widespread process occurring in plants, fungi, protists, and invertebrates. Saccharomyces cerevisiae has proved to be an excellent model to dissect mitochondrial biology. Several studies have focused on DNA recombination in this organelle, yet mostly relied on reporter genes or artificial systems. However, no complete mitochondrial recombination map has been released for any eukaryote so far. In the present work, we sequenced pools of diploids originating from a cross between two different S. cerevisiae strains to detect recombination events. This strategy allowed us to generate the first genome-wide map of recombination for yeast mitochondrial DNA. We demonstrated that recombination events are enriched in specific hotspots preferentially localized in non-protein-coding regions. Additionally, comparison of the recombination profiles of two different crosses showed that the genetic background affects hotspot localization and recombination rates. Finally, to gain insights into the mechanisms involved in mitochondrial recombination, we assessed the impact of individual depletion of four genes previously associated with this process. Deletion of NTG1 and MGT1 did not substantially influence the recombination landscape, alluding to the potential presence of additional regulatory factors. Our findings also revealed the loss of large mitochondrial DNA regions in the absence of MHR1, suggesting a pivotal role for Mhr1 in mitochondrial genome maintenance during mating. This study provides a comprehensive overview of mitochondrial DNA recombination in yeast and thus paves the way for future mechanistic studies of mitochondrial recombination and genome maintenance.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1534/genetics.114.166637

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The identical mitochondrial genomes of the Swiss and clinical C. subhashii isolates are in contrast to studies reporting considerable intra-species variation in size, intron content, and recombination in fungal mitochondrial genomes.

    “the identical mitochondrial genomes are in contrast to studies reporting considerable intra-species variation in size, intron content, and recombination in fungal mitochondrial genomes [104–106].”

    From Competition assays and physiological experiments of soil and phyllosphere yeasts identify Candida subhashii as a novel antagonist of filamentous fungi (2017) · cites this paper as [105]

    The Results section, “Intraspecies variability influences recombination hotspot profiles” (page unavailable), reports differences in mitochondrial recombination rates and hotspots between S. cerevisiae crosses. The Discussion section, “The genetic background influences mitochondrial recombination” (page unavailable), notes an additional COX1 intron in one strain. These passages support variation in recombination and intron content, but do not establish intra-species variation in mitochondrial genome size. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 79

  1. Arrieta-Montiel M. P. Shedge V. Davila J. Christensen A. C. Mackenzie S. A., 2009 Diversity of the Arabidopsis mitochondrial genome occurs via nuclear-controlled recombination activity. Genetics 183: 1261– 1268 19822729 PMC2787419
  2. Baudat F. Nicolas A., 1997 Clustering of meiotic double-strand breaks on yeast chromosome III. Proc. Natl. Acad. Sci. USA 94: 5213– 5218 9144217 PMC24658
  3. Benjamini Y. Hochberg Y., 1995 Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57(1): 289– 300
  4. Bianchi N. O. Bianchi M. S. Richard S. M., 2001 Mitochondrial genome instability in human cancers. Mutat. Res. 488: 9– 23 11223402
  5. Brewer L. R. Friddle R. Noy A. Baldwin E. Martin S. S., 2003 Packaging of single DNA molecules by the yeast mitochondrial protein Abf2p. Biophys. J. 85: 2519– 2524 14507714 PMC1303475
  6. Buhler C. Shroff R. Lichten M., 2009 Genome-wide mapping of meiotic DNA double-strand breaks in Saccharomyces cerevisiae. Methods Mol. Biol. 557: 143– 164 19799181
  7. Chen X. J. Butow R. A., 2005 The organization and inheritance of the mitochondrial genome. Nat. Rev. Genet. 6: 815– 825 16304597
  8. Clark-Walker G. D., 1991 Contrasting mutation rates in mitochondrial and nuclear genes of yeasts vs. mammals. Curr. Genet. 20: 195– 198 1657417
  9. D’aurelio M., 2004 Heterologous mitochondrial DNA recombination in human cells. Hum. Mol. Genet. 13: 3171– 3179 15496432
  10. Davila J. I. Arrieta-Montiel M. P. Wamboldt Y. Cao J. Hagmann J., 2011 Double-strand break repair processes drive evolution of the mitochondrial genome in Arabidopsis. BMC Biol. 9: 64 21951689 PMC3193812
  11. Defontaine A. Lecocq F. M. Hallet J. N., 1991 A rapid miniprep method for the preparation of yeast mitochondrial DNA. Nucleic Acids Res. 19: 185 2011504 PMC333555
  12. de Zamaroczy M. Bernardi G., 1986 The GC clusters of the mitochondrial genome of yeast and their evolutionary origin. Gene 41: 1– 22 3009268
  13. Dieckmann C. L. Gandy B., 1987 Preferential recombination between GC clusters in yeast mitochondrial DNA. EMBO J. 6: 4197– 4203 3327690 PMC553904
  14. Dimitrov L., R. Brem, L. Kruglyak, and D. Gottschling, 2009 Polymorphisms in multiple genes contribute to the spontaneous mitochondrial genome instability of Saccharomyces cerevisiae S288C strains. Genetics 183: 365–383. PMC2746160 19581448
  15. Doudican N. A. Song B. Shadel G. S. Doetsch P. W., 2005 Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae. Mol. Cell. Biol. 25: 5196– 5204 15923634 PMC1140570
  16. Dujon B. Slonimski P. P. Weill L., 1974 Mitochondrial genetics IX: a model for recombination and segregation of mitochondrial genomes in Saccharomyces cerevisiae. Genetics 78: 415 4613610 PMC1213202
  17. Eyre-Walker A. Awadalla P., 2001 Does human mtDNA recombine? J. Mol. Evol. 53: 430– 435 11675602
  18. Ezekiel U. R. Zassenhaus H. P., 1993 Localization of a cruciform cutting endonuclease to yeast mitochondria. Mol. Gen. Genet. 240: 414– 418 8413191
  19. Fikus M. U. Mieczkowski P. A. Koprowski P. Rytka J. Sledziewska-Gójska E., 2000 The product of the DNA damage-inducible gene of Saccharomyces cerevisiae, DIN7, specifically functions in mitochondria. Genetics 154: 73– 81 10628970 PMC1460913
  20. Fourie G. van der Merwe N. A. Wingfield B. D. Bogale M. Tudzynski B., 2013 Evidence for inter-specific recombination among the mitochondrial genomes of Fusarium species in the Gibberella fujikuroi complex. BMC Genomics 14: 605 24010864 PMC3847072
  21. Foury F. Roganti T. Lecrenier N. Purnelle B., 1998 The complete sequence of the mitochondrial genome of Saccharomyces cerevisiae. FEBS Lett. 440: 325– 331 9872396
  22. Fukui H. Moraes C. T., 2009 Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging neurons. Hum. Mol. Genet. 18: 1028– 1036 19095717 PMC2722231
  23. Galtier N., 2011 The intriguing evolutionary dynamics of plant mitochondrial DNA. BMC Biol. 9: 61 21951676 PMC3181201
  24. Gerton J. L. DeRisi J. Shroff R. Lichten M. Brown P. O., 2000 Inaugural article: global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 97: 11383– 11390 11027339 PMC17209
  25. Gibb S. Strimmer K., 2012 MALDIquant: a versatile R package for the analysis of mass spectrometry data. Bioinformatics 28: 2270– 2271 22796955
  26. Gietz R. D. Schiestl R. H., 2007 a Frozen competent yeast cells that can be transformed with high efficiency using the LiAc/SS carrier DNA/PEG method. Nat. Protoc. 2: 1– 4 17401330
  27. Gietz R. D. Schiestl R. H., 2007 b High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method. Nat. Protoc. 2: 31– 34 17401334
  28. Goffeau, A., B. G. Barrell, H. Bussey, R. W. Davis, B. Dujon et al, 1996 Life with 6000 genes. Science 274: 546, 563–567. 8849441
  29. Gray M. W. Burger G. Lang B. F., 1999 Mitochondrial evolution. Science 283: 1476– 1481 10066161
  30. Hori A. Yoshida M. Shibata T. Ling F., 2009 Reactive oxygen species regulate DNA copy number in isolated yeast mitochondria by triggering recombination-mediated replication. Nucleic Acids Res. 37: 749– 761 19074198 PMC2647299
  31. Jacquier A. Dujon B., 1985 An intron-encoded protein is active in a gene conversion process that spreads an intron into a mitochondrial gene. Cell 41: 383– 394 3886163
  32. Jung P. P. Schacherer J. Souciet J.-L. Potier S. Wincker P., 2009 The complete mitochondrial genome of the yeast Pichia sorbitophila. FEMS Yeast Res. 9: 903– 910 19594828
  33. Jung, P. P., A. Friedrich, C. Reisser, J. Hou, and J. Schacherer, 2012 Mitochondrial genome evolution in a single protoploid yeast species. G3 2: 1103–1111. PMC3429925 22973548
  34. Kalifa L. Quintana D. F. Schiraldi L. K. Phadnis N. Coles G. L., 2012 Mitochondrial genome maintenance: roles for nuclear nonhomologous end joining proteins in Saccharomyces cerevisiae. Genetics 190: 951– 964 22214610 PMC3296257
  35. Kleff S. Kemper B. Sternglanz R., 1992 Identification and characterization of yeast mutants and the gene for a cruciform cutting endonuclease. EMBO J. 11: 699– 704 1537343 PMC556502
  36. Kong A. Thorleifsson G. Gudbjartsson D. F. Masson G. Sigurdsson A., 2010 Fine-scale recombination rate differences between sexes, populations and individuals. Nature 467: 1099– 1103 20981099
  37. Kraytsberg Y. Schwartz M. Brown T. A. Ebralidse K. Kunz W. S., 2004 Recombination of human mitochondrial DNA. Science 304: 981 15143273
  38. Kucej M. Kucejova B. Subramanian R. Chen X. J. Butow R. A., 2008 Mitochondrial nucleoids undergo remodeling in response to metabolic cues. J. Cell Sci. 121: 1861– 1868 18477605 PMC5728373
  39. Ladoukakis E. D. Zouros E., 2001 Direct evidence for homologous recombination in mussel (Mytilus galloprovincialis) mitochondrial DNA. Mol. Biol. Evol. 18: 1168– 1175 11420358
  40. Lakshmipathy U. Campbell C., 1999 The human DNA ligase III gene encodes nuclear and mitochondrial proteins. Mol. Cell. Biol. 19: 3869– 3876 10207110 PMC84244
  41. Lee H.-C. Yin P.-H. Lin J.-C. Wu C.-C. Chen C.-Y., 2006 Mitochondrial genome instability and mtDNA depletion in human cancers. Ann. N. Y. Acad. Sci. 1042: 109– 122 15965052
  42. Lee H.-Y. Chou J.-Y. Cheong L. Chang N.-H. Yang S.-Y., 2008 Incompatibility of nuclear and mitochondrial genomes causes hybrid sterility between two yeast species. Cell 135: 1065– 1073 19070577
  43. Ling F. Shibata T., 2002 Recombination-dependent mtDNA partitioning: in vivo role of Mhr1p to promote pairing of homologous DNA. EMBO J. 21: 4730– 4740 12198175 PMC126199
  44. Ling F. Makishima F. Morishima N. Shibata T., 1995 A nuclear mutation defective in mitochondrial recombination in yeast. EMBO J. 14: 4090– 4101 7664749 PMC394488
  45. Ling F. Morioka H. Ohtsuka E. Shibata T., 2000 A role for MHR1, a gene required for mitochondrial genetic recombination, in the repair of damage spontaneously introduced in yeast mtDNA. Nucleic Acids Res. 28: 4956– 4963 11121487 PMC115238
  46. Ling F. Hori A. Shibata T., 2007 DNA recombination-initiation plays a role in the extremely biased inheritance of yeast [rho-] mitochondrial DNA that contains the replication origin ori5. Mol. Cell. Biol. 27: 1133– 1145 17116696 PMC1800698
  47. Ling F. Mikawa T. Shibata T., 2011 Enlightenment of yeast mitochondrial homoplasmy: diversified roles of gene conversion. Genes 2: 169– 190 24710143 PMC3924846
  48. Ling F. Hori A. Yoshitani A. Niu R. Yoshida M., 2013 Din7 and Mhr1 expression levels regulate double-strand-break-induced replication and recombination of mtDNA at ori5 in yeast. Nucleic Acids Res. 41: 5799–5816. PMC3675488 23598996
  49. Lockshon D. Zweifel S. G. Freeman-Cook L. L. Lorimer H. E. Brewer B. J., 1995 A role for recombination junctions in the segregation of mitochondrial DNA in yeast. Cell 81: 947– 955 7781070
  50. Lynch M. Blanchard J. L., 1998 Deleterious mutation accumulation in organelle genomes. Genetica 102–103: 29– 39 9720269
  51. Macreadie I. G. Scott R. M. Zinn A. R. Butow R. A., 1985 Transposition of an intron in yeast mitochondria requires a protein encoded by that intron. Cell 41: 395– 402 3886164
  52. Mancera E. Bourgon R. Brozzi A. Huber W. Steinmetz L. M., 2008 High-resolution mapping of meiotic crossovers and non-crossovers in yeast. Nature 454: 479– 485 18615017 PMC2780006
  53. McKenna A. Hanna M. Banks E. Sivachenko A. Cibulskis K., 2010 The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20: 1297– 1303 20644199 PMC2928508
  54. Mieczkowski P. A. Fikus M. U. Ciesla Z., 1997 Characterization of a novel DNA damage-inducible gene of Saccharomyces cerevisiae, DIN7, which is a structural homolog of the RAD2 and RAD27 DNA repair genes. Mol. Gen. Genet. 253: 655– 665 9079876
  55. Munz P. Amstutz H. Kohli J. Leupold U., 1982 Recombination between dispersed serine tRNA genes in Schizosaccharomyces pombe. Nature 300: 225– 231 6924071
  56. Petes T. D., 2001 Meiotic recombination hot spots and cold spots. Nat. Rev. Genet. 2: 360– 369 11331902
  57. Pérez-Martínez X. Broadley S. A. Fox T. D., 2003 Mss51p promotes mitochondrial Cox1p synthesis and interacts with newly synthesized Cox1p. EMBO J. 22: 5951– 5961 14592991 PMC275423
  58. Phadnis N. Mehta R. Meednu N. Sia E. A., 2006 Ntg1p, the base excision repair protein, generates mutagenic intermediates in yeast mitochondrial DNA. DNA Repair 5: 829– 839 16730479
  59. Pratt-Hyatt M. J. Kapadia K. M. Wilson T. E. Engelke D. R., 2006 Increased recombination between active tRNA genes. DNA Cell Biol. 25: 359– 364 16792506 PMC3756803
  60. Preuten T. Cincu E. Fuchs J. Zoschke R. Liere K., 2010 Fewer genes than organelles: extremely low and variable gene copy numbers in mitochondria of somatic plant cells. Plant J. 64: 948– 959 21143676
  61. Shay J. W. Pierce D. J. Werbin H., 1990 Mitochondrial DNA copy number is proportional to total cell DNA under a variety of growth conditions. J. Biol. Chem. 265: 14802– 14807 2394698
  62. Shibata T. Ling F., 2007 DNA recombination protein-dependent mechanism of homoplasmy and its proposed functions. Mitochondrion 7: 17– 23 17280877
  63. Solieri L., 2010 Mitochondrial inheritance in budding yeasts: towards an integrated understanding. Trends Microbiol. 18: 521– 530 20832322
  64. Solieri L. Antúnez O. Pérez Ortín J. E. Barrio E. Giudici P., 2008 Mitochondrial inheritance and fermentative: oxidative balance in hybrids between Saccharomyces cerevisiae and Saccharomyces uvarum. Yeast 25: 485– 500 18615860
  65. Song S. Pursell Z. F. Copeland W. C. Longley M. J. Kunkel T. A., 2005 DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelity. Proc. Natl. Acad. Sci. USA 102: 4990– 4995 15784738 PMC555996
  66. Storici F. Lewis L. K. Resnick M. A., 2001 In vivo site-directed mutagenesis using oligonucleotides. Nat. Biotechnol. 19: 773– 776 11479573
  67. Strausberg R. L. Butow R. A., 1981 Gene conversion at the VAR1 locus on yeast mitochondrial DNA. Proc. Natl. Acad. Sci. USA 78: 494– 498 7017717 PMC319080
  68. Strausberg R. L. Perlman P. S., 1978 The effect of zygotic bud position on the transmission of mitochondrial genes in Saccharomyces cerevisiae. Mol. Gen. Genet. 163: 131– 144 355844
  69. Strausberg R. L. Vincent R. D. Perlman P. S. Butow R. A., 1978 Asymmetric gene conversion at inserted segments on yeast mitochondrial DNA. Nature 276: 577– 583 364319
  70. Székvölgyi L. Nicolas A., 2010 From meiosis to postmeiotic events: homologous recombination is obligatory but flexible. FEBS J. 277: 571– 589 20015080
  71. Wahls, W. P., E. R. Siegel, and M. K. Davidson, 2008 Meiotic recombination hotspots of fission yeast are directed to loci that express non-coding RNA. PLoS ONE 3: e2887. PMC2483352 18682829
  72. Wallace D. C., 2007 Why do we still have a maternally inherited mitochondrial DNA? Insights from evolutionary medicine. Annu. Rev. Biochem. 76: 781– 821 17506638
  73. Wei W. McCusker J. H. Hyman R. W. Jones T. Ning Y., 2007 Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789. Proc. Natl. Acad. Sci. USA 104: 12825– 12830 17652520 PMC1933262
  74. White M. F. Lilley D. M., 1997 The resolving enzyme CCE1 of yeast opens the structure of the four-way DNA junction. J. Mol. Biol. 266: 122– 134 9054975
  75. Wilkening S. Tekkedil M. M. Lin G. Fritsch E. S. Wei W., 2013 Genotyping 1000 yeast strains by next-generation sequencing. BMC Genomics 14: 90 23394869 PMC3575377
  76. Wu T. D. Watanabe C. K., 2005 GMAP: a genomic mapping and alignment program for mRNA and EST sequences. Bioinformatics 21: 1859– 1875 15728110
  77. Zeyl C. Andreson B. Weninck E., 2005 Nuclear-mitochondrial epistasis for fitness in Saccharomyces cerevisiae. Evolution 59: 910– 914 15926700
  78. Zinn A. R. Butow R. A., 1985 Nonreciprocal exchange between alleles of the yeast mitochondrial 21S rRNA gene: kinetics and the involvement of a double-strand break. Cell 40: 887– 895 3886160
  79. Zinn A. R. Pohlman J. K. Perlman P. S. Butow R. A., 1987 Kinetic and segregational analysis of mitochondrial DNA recombination in yeast. Plasmid 17: 248– 256 3306735

Cited by

Sorted by citations

Authors
Fritsch, E. S., Chabbert, C. D., Klaus, B., & Steinmetz, L. M.
Affiliations
  • European Molecular Biology Laboratory (DE)
  • Stanford Medicine (US)
Corresponding author
Steinmetz, Lars M
Venue
Genetics
Published
2014-07-31
Volume
198
Issue
2
Pages
755-771
ISSN
  • 0016-6731 (ISSN-L)
  • 1943-2631
OpenAlex
W2021051845
Cited by
77
References
4
Citations by year
2026: 2 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 8 · 2018: 5 · 2017: 12 · 2016: 4 · 2015: 9
FWCI
3.42
Type
journal article
Language
en
Open access
Locations
  • Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
mitochondrial recombination, Saccharomyces cerevisiae, recombination hotspots, mitochondrial DNA maintenance, genetic background effects, mitochondrial DNA loss, mating
MeSH terms
Chromosome Mapping, DNA, Mitochondrial, Recombination, Genetic, Saccharomyces cerevisiae, Genome, Fungal, Sequence Analysis, DNA, Mutation Rate

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review