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. 1996 Apr 1;15(7):1726–1733.

The mismatch repair system contributes to meiotic sterility in an interspecific yeast hybrid.

N Hunter 1, S R Chambers 1, E J Louis 1, R H Borts 1
PMCID: PMC450085  PMID: 8612597

Abstract

The mismatch repair system is the major barrier to genetic recombination during interspecific sexual conjugation in prokaryotes. The existence of this anti-recombination activity has implications for theories of evolution and the isolation of species. To determine if this phenomenon occurs in eukaryotes, the effect of a deficiency of mismatch repair on the meiotic sterility of an interspecific hybrid of Saccharomyces cerevisiae and the closely related species Saccharomyces paradoxus was examined. The results demonstrate that the rare viable spores from these hybrids have high frequencies of aneuploidy and low frequencies of genetic exchange. Hybrids lacking mismatch repair genes PMS1 or MSH2 display increased meiotic recombination, decreased chromosome non-disjunction and improved spore viability. These observations are consistent with the proposal that the mismatch repair system is an element of the genetic barrier between eukaryotic species. We suggest that an anti-recombination activity during meiosis contributes towards the establishment of post-zygotic species barriers.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adjiri A., Chanet R., Mezard C., Fabre F. Sequence comparison of the ARG4 chromosomal regions from the two related yeasts, Saccharomyces cerevisiae and Saccharomyces douglasii. Yeast. 1994 Mar;10(3):309–317. doi: 10.1002/yea.320100304. [DOI] [PubMed] [Google Scholar]
  2. Alani E., Reenan R. A., Kolodner R. D. Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae. Genetics. 1994 May;137(1):19–39. doi: 10.1093/genetics/137.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bailis A. M., Rothstein R. A defect in mismatch repair in Saccharomyces cerevisiae stimulates ectopic recombination between homeologous genes by an excision repair dependent process. Genetics. 1990 Nov;126(3):535–547. doi: 10.1093/genetics/126.3.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bishop D. K., Park D., Xu L., Kleckner N. DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression. Cell. 1992 May 1;69(3):439–456. doi: 10.1016/0092-8674(92)90446-j. [DOI] [PubMed] [Google Scholar]
  5. Borts R. H., Haber J. E. Meiotic recombination in yeast: alteration by multiple heterozygosities. Science. 1987 Sep 18;237(4821):1459–1465. doi: 10.1126/science.2820060. [DOI] [PubMed] [Google Scholar]
  6. Borts R. H., Leung W. Y., Kramer W., Kramer B., Williamson M., Fogel S., Haber J. E. Mismatch repair-induced meiotic recombination requires the pms1 gene product. Genetics. 1990 Mar;124(3):573–584. doi: 10.1093/genetics/124.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Collins I., Newlon C. S. Meiosis-specific formation of joint DNA molecules containing sequences from homologous chromosomes. Cell. 1994 Jan 14;76(1):65–75. doi: 10.1016/0092-8674(94)90173-2. [DOI] [PubMed] [Google Scholar]
  8. DasGupta C., Radding C. M. Lower fidelity of RecA protein catalysed homologous pairing with a superhelical substrate. Nature. 1982 Jan 7;295(5844):71–73. doi: 10.1038/295071a0. [DOI] [PubMed] [Google Scholar]
  9. Datta A., Adjiri A., New L., Crouse G. F., Jinks Robertson S. Mitotic crossovers between diverged sequences are regulated by mismatch repair proteins in Saccaromyces cerevisiae. Mol Cell Biol. 1996 Mar;16(3):1085–1093. doi: 10.1128/mcb.16.3.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Doutriaux M. P., Wagner R., Radman M. Mismatch-stimulated killing. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2576–2578. doi: 10.1073/pnas.83.8.2576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gietz D., St Jean A., Woods R. A., Schiestl R. H. Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res. 1992 Mar 25;20(6):1425–1425. doi: 10.1093/nar/20.6.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hawthorne D., Philippsen P. Genetic and molecular analysis of hybrids in the genus Saccharomyces involving S. cerevisiae, S. uvarum and a new species, S. douglasii. Yeast. 1994 Oct;10(10):1285–1296. doi: 10.1002/yea.320101005. [DOI] [PubMed] [Google Scholar]
  13. Herbert C. J., Dujardin G., Labouesse M., Slonimski P. P. Divergence of the mitochondrial leucyl tRNA synthetase genes in two closely related yeasts Saccharomyces cerevisiae and Saccharomyces douglasii: a paradigm of incipient evolution. Mol Gen Genet. 1988 Aug;213(2-3):297–309. doi: 10.1007/BF00339595. [DOI] [PubMed] [Google Scholar]
  14. Kolodner R. D. Mismatch repair: mechanisms and relationship to cancer susceptibility. Trends Biochem Sci. 1995 Oct;20(10):397–401. doi: 10.1016/s0968-0004(00)89087-8. [DOI] [PubMed] [Google Scholar]
  15. Kramer W., Kramer B., Williamson M. S., Fogel S. Cloning and nucleotide sequence of DNA mismatch repair gene PMS1 from Saccharomyces cerevisiae: homology of PMS1 to procaryotic MutL and HexB. J Bacteriol. 1989 Oct;171(10):5339–5346. doi: 10.1128/jb.171.10.5339-5346.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lichten M., Borts R. H., Haber J. E. Meiotic gene conversion and crossing over between dispersed homologous sequences occurs frequently in Saccharomyces cerevisiae. Genetics. 1987 Feb;115(2):233–246. doi: 10.1093/genetics/115.2.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lichten M., Goyon C., Schultes N. P., Treco D., Szostak J. W., Haber J. E., Nicolas A. Detection of heteroduplex DNA molecules among the products of Saccharomyces cerevisiae meiosis. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7653–7657. doi: 10.1073/pnas.87.19.7653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matic I., Rayssiguier C., Radman M. Interspecies gene exchange in bacteria: the role of SOS and mismatch repair systems in evolution of species. Cell. 1995 Feb 10;80(3):507–515. doi: 10.1016/0092-8674(95)90501-4. [DOI] [PubMed] [Google Scholar]
  19. McCusker J. H., Haber J. E. Cycloheximide-resistant temperature-sensitive lethal mutations of Saccharomyces cerevisiae. Genetics. 1988 Jun;119(2):303–315. doi: 10.1093/genetics/119.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mortimer R. K., Contopoulou C. R., King J. S. Genetic and physical maps of Saccharomyces cerevisiae, Edition 11. Yeast. 1992 Oct;8(10):817–902. doi: 10.1002/yea.320081002. [DOI] [PubMed] [Google Scholar]
  21. Naumov G. I., Naumova E. S., Lantto R. A., Louis E. J., Korhola M. Genetic homology between Saccharomyces cerevisiae and its sibling species S. paradoxus and S. bayanus: electrophoretic karyotypes. Yeast. 1992 Aug;8(8):599–612. doi: 10.1002/yea.320080804. [DOI] [PubMed] [Google Scholar]
  22. New L., Liu K., Crouse G. F. The yeast gene MSH3 defines a new class of eukaryotic MutS homologues. Mol Gen Genet. 1993 May;239(1-2):97–108. doi: 10.1007/BF00281607. [DOI] [PubMed] [Google Scholar]
  23. Parry E. M., Cox B. S. The tolerance of aneuploidy in yeast. Genet Res. 1970 Dec;16(3):333–340. doi: 10.1017/s0016672300002597. [DOI] [PubMed] [Google Scholar]
  24. Petit M. A., Dimpfl J., Radman M., Echols H. Control of large chromosomal duplications in Escherichia coli by the mismatch repair system. Genetics. 1991 Oct;129(2):327–332. doi: 10.1093/genetics/129.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Prolla T. A., Pang Q., Alani E., Kolodner R. D., Liskay R. M. MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast. Science. 1994 Aug 19;265(5175):1091–1093. doi: 10.1126/science.8066446. [DOI] [PubMed] [Google Scholar]
  26. Radman M. Mismatch repair and the fidelity of genetic recombination. Genome. 1989;31(1):68–73. doi: 10.1139/g89-014. [DOI] [PubMed] [Google Scholar]
  27. Radman M., Wagner R. Mismatch recognition in chromosomal interactions and speciation. Chromosoma. 1993 Jun;102(6):369–373. doi: 10.1007/BF00360400. [DOI] [PubMed] [Google Scholar]
  28. Rayssiguier C., Thaler D. S., Radman M. The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature. 1989 Nov 23;342(6248):396–401. doi: 10.1038/342396a0. [DOI] [PubMed] [Google Scholar]
  29. Reenan R. A., Kolodner R. D. Characterization of insertion mutations in the Saccharomyces cerevisiae MSH1 and MSH2 genes: evidence for separate mitochondrial and nuclear functions. Genetics. 1992 Dec;132(4):975–985. doi: 10.1093/genetics/132.4.975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Reenan R. A., Kolodner R. D. Isolation and characterization of two Saccharomyces cerevisiae genes encoding homologs of the bacterial HexA and MutS mismatch repair proteins. Genetics. 1992 Dec;132(4):963–973. doi: 10.1093/genetics/132.4.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Resnick M. A., Zgaga Z., Hieter P., Westmoreland J., Fogel S., Nilsson-Tillgren T. Recombinant repair of diverged DNAs: a study of homoeologous chromosomes and mammalian YACs in yeast. Mol Gen Genet. 1992 Jul;234(1):65–73. doi: 10.1007/BF00272346. [DOI] [PubMed] [Google Scholar]
  32. Rockmill B., Roeder G. S. The yeast med1 mutant undergoes both meiotic homolog nondisjunction and precocious separation of sister chromatids. Genetics. 1994 Jan;136(1):65–74. doi: 10.1093/genetics/136.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rockmill B., Sym M., Scherthan H., Roeder G. S. Roles for two RecA homologs in promoting meiotic chromosome synapsis. Genes Dev. 1995 Nov 1;9(21):2684–2695. doi: 10.1101/gad.9.21.2684. [DOI] [PubMed] [Google Scholar]
  34. Roeder G. S. Chromosome synapsis and genetic recombination: their roles in meiotic chromosome segregation. Trends Genet. 1990 Dec;6(12):385–389. doi: 10.1016/0168-9525(90)90297-j. [DOI] [PubMed] [Google Scholar]
  35. Schwacha A., Kleckner N. Identification of double Holliday junctions as intermediates in meiotic recombination. Cell. 1995 Dec 1;83(5):783–791. doi: 10.1016/0092-8674(95)90191-4. [DOI] [PubMed] [Google Scholar]
  36. Schwacha A., Kleckner N. Identification of joint molecules that form frequently between homologs but rarely between sister chromatids during yeast meiosis. Cell. 1994 Jan 14;76(1):51–63. doi: 10.1016/0092-8674(94)90172-4. [DOI] [PubMed] [Google Scholar]
  37. Selva E. M., New L., Crouse G. F., Lahue R. S. Mismatch correction acts as a barrier to homeologous recombination in Saccharomyces cerevisiae. Genetics. 1995 Mar;139(3):1175–1188. doi: 10.1093/genetics/139.3.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shen P., Huang H. V. Homologous recombination in Escherichia coli: dependence on substrate length and homology. Genetics. 1986 Mar;112(3):441–457. doi: 10.1093/genetics/112.3.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  40. Williams C. E., Wielgus S. M., Haberlach G. T., Guenther C., Kim-Lee H., Helgeson J. P. RFLP analysis of chromosomal segregation in progeny from an interspecific hexaploid somatic hybrid between Solanum brevidens and Solanum tuberosum. Genetics. 1993 Dec;135(4):1167–1173. doi: 10.1093/genetics/135.4.1167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Williamson M. S., Game J. C., Fogel S. Meiotic gene conversion mutants in Saccharomyces cerevisiae. I. Isolation and characterization of pms1-1 and pms1-2. Genetics. 1985 Aug;110(4):609–646. doi: 10.1093/genetics/110.4.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Worth L., Jr, Clark S., Radman M., Modrich P. Mismatch repair proteins MutS and MutL inhibit RecA-catalyzed strand transfer between diverged DNAs. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3238–3241. doi: 10.1073/pnas.91.8.3238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Xu L., Kleckner N. Sequence non-specific double-strand breaks and interhomolog interactions prior to double-strand break formation at a meiotic recombination hot spot in yeast. EMBO J. 1995 Oct 16;14(20):5115–5128. doi: 10.1002/j.1460-2075.1995.tb00194.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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