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The detection of mitotic and meiotic aneuploidy in yeast using a gene dosage selection system

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Summary

A system is described in which spontaneous and chemically-induced mitotic and meiotic hyperploidy can be assayed in the same diploid culture of Saccharomyces cerevisiae. Monitoring gene dosage changes at two loci on chromosome VIII, the test utilizes a leaky temperature-sensitive allele arg4-8 and low level copper resistance conferred by the single copy allele cup1 s. An extra chromosome VIII provides simultaneous increased dosage for both genes, resulting in colonies that are both prototrophic for arginine at 30° C and copper resistant. During mitotic cell divisions in diploids, spontaneous chromosome VIII hyperploids (trisomes and tetrasomes) occur at a frequency of 6.4×10-6 per viable cell. Among ascospores, the spontaneous chromosome VIII disome frequency is 5.5×10-6 per viable spore. The tubulin-binding reagent methyl benzimidazol-2-yl carbamate (MBC) elicits enhanced levels of mitotic and meiotic aneuploidy relative to control levels. The system represents a novel model for examining chromosome behavior during mitosis and meiosis and provides a sensitive and quantifiable procedure for examining chemically induced aneuploidy.

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References

  • Bellincampi D, Gualandi G, Lamonica E, Poley C, Morpurgo G (1980) Membrane-damaging agents cause mitotic nondisjunction in A. nidulans. Mutat Res 79:169–172

    Google Scholar 

  • Beyer WH (1966) Confidence intervals for medians, Table VII.3. In: Handbook of tables for probability and statistics. CRC Press, p 266, Cleveland, Ohio, USA

    Google Scholar 

  • Bond DJ, McMillan L (1979) Meiotic aneuploidy: its origins and induction following chemical treatment in Sordaria brevicollis. Environ Health Perspect 31:67–74

    Google Scholar 

  • Boveri T (1907) Zellenstudien VI. Die Entwicklung dispermer Seeigeleier. Ein Beitrag zur Befruchtungslehre und zur Theorie des Kerns. Jena Z 37:1–292

    Google Scholar 

  • Brenes-Pomales A, Lindegren G, Lindegren CC (1955) Genetic control of copper sensitivity in Saccharomyces. Nature (London) 176:841–842

    Google Scholar 

  • Breunn J, Mortimer RK (1970) Isolation of monosomics in yeast. J Bacteriol 102:548–551

    Google Scholar 

  • Bridges CB (1916) Non-disjunction as proof of the chromosome theory of heredity. Genetics 1:1–52, 107–163

    Google Scholar 

  • Campbell DA, Fogel S, Lusnak K (1974) Mitotic chromosome loss in a disomic haploid of Saccharomyces cerevisiae. Genetics 79:383–396

    Google Scholar 

  • Culbertson MR, Henry SA (1973) Genetic analysis of hybrid strains disomic for the chromosome containing a fatty acid synthetase gene complex (fas1) in yeast. Genetics 75:441–458

    Google Scholar 

  • Darlington CD (1939) Misdivision and the genetics of the centromere. J Genet 37:341–364

    Google Scholar 

  • De Bertoldi M, Griselli M (1980) Different test systems in Aspergillus nidulans for the evaluation of mitotic gene conversion, crossing-over and non-disjunction. Mutat Res 74:303–324

    Google Scholar 

  • Dobzhansky T (1941) Genetics and the origin of species. Columbia University Press, New York

    Google Scholar 

  • Finkelstein DB, Blamire J, Marmur J (1972) Location of ribosomal RNA cistons in yeast. Nature New Biol 240:279–281

    Google Scholar 

  • Fogel S, Roth R (1974) Mutations affecting meiotic gene conversion in yeast. Mol Gen Genet 130:189–201

    Google Scholar 

  • Fogel S, Welch JW (1982) Tandem gene amplification mediates copper resistance in yeast. Proc Natl Acad Sci USA 79:5342–5346

    Google Scholar 

  • Foureman PA (1979) A translocation X; Y system for detecting meiotic nondisjunction and chromosome breakage in males of Drosophila melanogaster. Environ Health Perspect 31:53–58

    Google Scholar 

  • Goldberg S, Oyen T, Idriss JM, Halvorson HO (1972) Use of disomic strains to study the arrangement of ribosomal cistrons in Saccharomyces cerevisiae. Mol Gen Genet 116:139–157

    Google Scholar 

  • Grell RF (1979) Origin of meiotic con-disjunction in Drosophila females. Environ Health Perspect 31:33–40

    Google Scholar 

  • Griffiths AJF (1979) Neurospora prototroph selection system for studying aneuploidy production. Environ Health Perspect 31:75–80

    Google Scholar 

  • Gualandi G, Bellincampi D, Puppo S (1979) MMS induction of different types of genetic damage in Aspergillus nidulans: a comparative analysis in mutagenesis. Mutat Res 62:255–266

    Google Scholar 

  • Haber JE (1974) Bisexual mating behaviour in Saccharomyces cerevisiae: evidence for genetically controlled nonrandom chromosome loss during vegetative growth. Genetics 78:843–858

    Google Scholar 

  • Hartwell LH, Smith D (1985) Altered fidelity of mitotic chromosome transmission in cell cycle mutants of S. cerevisiae. Genetics 110:381–395

    Google Scholar 

  • Kawasaki G (1979) Dissertation, Karyotypic instability and carbon source effects in cell cycle mutants of S. cerevisiae. University of Washington, Scattle

    Google Scholar 

  • Lea DE, Coulson CA (1949) The distribution of the numbers of mutants in bacterial populations. J Genet 49:264–285

    Google Scholar 

  • Leigh B (1979) Mechanisms of non-disjunction induction in Drosophila oocytes. Environ Health Perspect 31:41–44

    Google Scholar 

  • Libby WJ, Stettler RF, Seitz FW (1969) Forest genetics and forest-tree breeding. Annu Rev Genet 3:469–494

    Google Scholar 

  • Liras P, McCusker J, Mascioli S, Haber JE (1978) Characterization of a mutation in yeast causing nonrandom chromosome loss during mitosis. Genetics 88:651–671

    Google Scholar 

  • Maloney D, Fogel S (1980) Mitotic recombination in yeast: isolation and characterization of mutants with enhanced spontaneous mitotic gene conversion rates. Genetics 94:825–839

    Google Scholar 

  • Meeks-Wagner D, Hartwell LH (1986) Normal stoichiometry of histone dimer sets is necessary for high fidelity of mitotic chromosome transmission. Cell 44:43–52

    Google Scholar 

  • Meeks-Wagner D, Wood J, Garvik B, Hartwell LH (1986) Isolation of two genes that affect mitotic chromosome transmission in S. cerevisiae. Cell 44:53–63

    Google Scholar 

  • Morpurgo G, Bellincampi D, Gualandi G, Baldinelli L, Crescenzi OS (1979) Analysis of mitotic nondisjunction with Aspergillus nidulans. Environ Health Perspect 31:81–96

    Google Scholar 

  • Morrisson DP, Hastings PJ (1979) Characterization of the mutator mutation mut5-1. Mol Gen Genet 175:57–65

    Google Scholar 

  • Mortimer RK, Hawthorne DC (1973) Genetic mapping in Saccharomyces IV. Mapping of temperature-sensitive genes and use of disomic strains in localizing genes. Genetics 74:33–54

    Google Scholar 

  • Mortimer RK, Contopoulou R, Schild D (1981) Mitotic chromosome loss in a radiation-sensitive strain of the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci USA 78:5778–5782

    Google Scholar 

  • Neff NF, Thomas JH, Grisaffi P, Botstein D (1983) Isolation of the B-tubulin gene from yeast and demonstration of its essential function in vivo. Cell 33:211–219

    Google Scholar 

  • Onfelt A, Ramel C (1979) Some aspects on the organization of microfilaments and microtubules in relation to nondisjunction. Environ Health Perspect 31:45–52

    Google Scholar 

  • Parry EM, Cox BS (1971) The tolerance of aneuploidy in yeast. Genet Res 16:333–340

    Google Scholar 

  • Petes TD, Newlon CS, Byers B, Fangman WL (1973) Yeast chromosomal DNA: Size, structure and replication. Cold Spring Harbor Symp Quant Biol 38:9–16

    Google Scholar 

  • Ramel C, Magnusson J (1979) Chemical induction of nondisjunction in Drosophila. Environ Health Perspect 31:59–66

    Google Scholar 

  • Resnick MA, Mayer VM, Zimmerman FK (1986) The detection of chemically induced aneuploidy in Saccharomyces cerevisiae: An assessment of mitotic and meiotic systems. Mutat Res 167:47–60

    Google Scholar 

  • Rockmill BM (1985) Dissertation, Meiotic nondisjunction mutants in yeast. University of California, Berkeley

    Google Scholar 

  • Rodarte-Ramon US, Mortimer RK (1972) Radiation-induced recombination in Saccharomyces cerevisiae: isolation and genetic study of recombination-deficient mutants. Radiat Res 49:133–147

    Google Scholar 

  • Roth R, Fogel S (1971) A system selective for yeast mutants deficient in meiotic recombination. Mol Gen Genet 112:295–305

    Google Scholar 

  • Shaffer B, Brearely I, Littlewood R, Fink GR (1971) A stable aneuploidy of Saccharomyces cerevisiae. Genetics 67:483–495

    Google Scholar 

  • Sheir-Neiss C, Lai MH, Morris NR (1978) Identification of a gene for B-tubulin in Aspergillus nidulans. Cell 16:437–442

    Google Scholar 

  • Smith PD (1983) A rapid selection technique for detecting meiotic chromosomal nondisjunction in Drosophila melanogaster. Mutat Res 108:169–174

    Google Scholar 

  • Stevens WL (1942) Accuracy of mutation rates. J Genet 43:301–307

    Google Scholar 

  • Stromnaes O (1968) Genetic changes in Saccharomyces cerevisiae grown on media containing D, L-parafluorophenylalanine. Hereditas 59:197–220

    Google Scholar 

  • Thomas JH, Botstein D (1986) A gene required for the separation of chromosome on the spindle apparatus of yeast. Cell 44:65–76

    Google Scholar 

  • Von Borstel RC (1978) Measuring spontaneous mutation rates in yeast. Methods Cell Biol 20:1–24

    Google Scholar 

  • Waters MD, Stack HF, Mavournin KH, Dellarco VL (1985) Quantitative evaluation of chemicals that induce aneuploidy using the genetic activity method. In: Dellarco VL, Voytek PE, Hollaender A (eds) Aneuploidy. Plenum, New York, pp 455–490

    Google Scholar 

  • White MJD (1973) Animal cytology and evolution, 3rd edition. Cambridge University Press, Cambridge, UK

    Google Scholar 

  • Williamson, MS, Game JC, Fogel S (1985) Meiotic gene conversion mutants in Saccharomyces cerevisiae. Isolation and characterization of pms1-1 and pms1-2. Genetics 110:609–646

    Google Scholar 

  • Wood JS (1982) Genetic effects of methylbenzimidazol-2-yl carbamate on Saccharomyces cerevisiae. Mol Cell Biol 2:1064–1079

    Google Scholar 

  • Zimmerman FK, Scheel I (1984) Genetic effects of 5-azacytidine in Saccharomyces cerevisiae. Mutat Res 139:21–24

    Google Scholar 

  • Zimmerman FK, Mayer VW, Scheel I, Resnick MA (1985) Acetone, methyl ethyl ketone, ethyl acetate, acetonitrile and other polar aprotic solvents are strong inducers of aneuploidy. Mutat Res 149:339–351

    Google Scholar 

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Communicated by G.R. Fink

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Whittaker, S.G., Rockmill, B.M., Blechl, A.E. et al. The detection of mitotic and meiotic aneuploidy in yeast using a gene dosage selection system. Mol Gen Genet 215, 10–18 (1988). https://doi.org/10.1007/BF00331296

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  • DOI: https://doi.org/10.1007/BF00331296

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