Current Genetics

, Volume 9, Issue 8, pp 627–640 | Cite as

The origin of mutant cells: mechanisms by whichSaccharomyces cerevisiae produces cells homoplasmic for new mitochondrial mutations

  • James S. Backer
  • C. William BirkyJr.


Haploid yeast cells have about 50 copies of the mitochondrial genome, and a mutational event is unlikely to affect more than one of these at a time. This raises the question of how such cells, or their progeny, become fixed (homoplasmic) for the mutant alele. We have tested the roles of six hypothetical mechanisms in producing erythromycin-resistant mutant cells: (i) random partitioning of mitochondrial genomes at cell division; (ii) intracellular selection for mtDNA molecules of one genotype; (iii) intracellular random drift of mitochondrial allele frequencies; (iv) intercellular selection for cells of a particular mitochondrial genotype; (v) induction of mitochondrial gene mutations by the antibiotic used to select mutants; and (vi) reduction in the number of mitochondrial genomes per cell by the antibiotic. Our experiments indicate that intracellular selection plays the major role in producing erythromycin-resistant mutant cells in the presence of the antibiotic. In the absence of the antibiotic, the combined effects of random drift and random partitioning are most important in determining the fate of new mutations, most of which are lost rather than fixed. Our experiments provide no evidence for mutation induction or ploidy reduction by erythromycin.

Key words

Mitochondria Mutation Yeast Selection Random drift 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Backer J (1980) The origin of mutant cells: the mechanisms by whichSaccharomyces cerevisiae produces cells homoplasmic for new mitochondrial mutations. PhD dissertation, The Ohio State UniversityGoogle Scholar
  2. Birky CW Jr (1973) Genetics 74:421–432Google Scholar
  3. Birky CW Jr (1978) Ann Rev Genet 12:471–512Google Scholar
  4. Birky CW Jr (1983) Int Rev Cytol Suppl 15:49–89Google Scholar
  5. Birky CW Jr, Demko CA, Perlman PS, Strausberg R (1978) Genetics 89:615–651Google Scholar
  6. Birky CW Jr, VanWinkle-Swift KP, Sears BB, Boynton JE, Gillham NW (1981) Plasmid 6:173–192Google Scholar
  7. Birky CW Jr, Acton AR, Dietrich R, Carver M (1982) In: Attardi GA, Borst P, Slonimski PP (eds) Mitochondrial genes. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp 333–348Google Scholar
  8. Birky CW Jr, Maruyama T, Fuerst P (1983) Genetics 103:513–527Google Scholar
  9. Bisson L, Thorner J (1977) J Bacteriol 132:44–50Google Scholar
  10. Dujon B (1981) In: Strathern JN, Jones EW, Broach JR (eds) The molecular biology of the yeast saccharomyces. Life cycle and inheritance. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp 505–635Google Scholar
  11. Dujon B, Bolotin-Fukuhara M, Coen D, Deutsch J, Netter P, Slonimski PP, Weill L (1976) Mol Gen Genet 143:131–165Google Scholar
  12. Gillham NW (1969) Am Nat 103:355–387Google Scholar
  13. Gillham NW (1978) Organelle heredity. Raven Press, New YorkGoogle Scholar
  14. Gillham NW, Boynton JE, Grant DM, Shepherd HS, Wurtz EA (1979) In: Cummings DJ (ed) 8th ICN-UCLA Symposia on Molecular and Cellular Biology: Extrachromosomal DNA. Academic Press, New York, pp 75–96Google Scholar
  15. Hartwell LH (1976) J Mol Biol 104:803–817Google Scholar
  16. Hartwell LH, Culotti J, Pringle JR, Reid BJ (1974) Science 183:46–51Google Scholar
  17. Johnston LH (1980) Curr Genet 2:175–180Google Scholar
  18. Karlin S (1975) Theor Pop Biol 7:364–398Google Scholar
  19. Knight JA (1980) Genetics 94:69–92Google Scholar
  20. Lee RW, Haughn GW (1980) Genetics 96:79–94Google Scholar
  21. Lewis JE, Birky CW Jr (1984) Curr Genet 8:81–84Google Scholar
  22. Luria SE, Delbruck M (1943) Genetics 28:491–511Google Scholar
  23. Newcombe HB (1949) Nature 164:150–151Google Scholar
  24. Newlon CS, Fangman WL (1975) Cell 5:423–428Google Scholar
  25. Putrament A, Baronowska H, Prazmo W (1973) Mol Gen Genet 126:357–366Google Scholar
  26. Putrament A, Polakowska R, Baranowska H, Ejchart A (1976) In: Bucher T, Neupert W, Sebald W, Werner S (eds) Genetics and biogenesis of chloroplasts and mitochondria. North Holland, Amsterdam, pp 415–418Google Scholar
  27. Rogers D, Bussey H (1978) Mol Gen Genet 162:173–182Google Scholar
  28. Sager R (1962) Proc Natl Acad Sci USA 48:2018–2026Google Scholar
  29. Sager R (1972) Cytoplsmic genes and organelles. Academic Press, New YorkGoogle Scholar
  30. Slater ML (1973) J Bacteriol 113:263–270Google Scholar
  31. Sloat FB, Pringle JR (1978) Science 200:1171–1173Google Scholar
  32. Thrailkill KM, Birky CW Jr, Luckeman G, Wolf K (1981) Genetics 96:237–262Google Scholar
  33. Treat L, Birky CW Jr (1980) Plasmid 4:261–275Google Scholar
  34. VanWinkle-Swift KP (1978) Nature 275:749–751Google Scholar
  35. Waxman MF, Birky CW Jr (1982) Curr Genet 5:171–180Google Scholar
  36. Williamson DH, Maroudas NG, Wilkie D (1971) Mol Gen Genet 111:209–223Google Scholar
  37. Williamson DH, Johnston LH, Richmond KMV, Game JC (1978) In: Bandlow W, Schweyen RJ, Wolf K, Kaudewitz F (eds) Mitochondria 1977: genetics and biogenesis of mitochondria. de Gruyter, Berlin, pp 1–24Google Scholar
  38. Wiseman A, Attardi G (1978a) Mol Gen Genet 167:51–63Google Scholar
  39. Wiseman A, Attardi G (1978b) J Cell Biol 79:321aGoogle Scholar
  40. Wurtz EA, Sears BB, Rabert DK, Shepherd HS, Gillham NW, Boynton JE (1979) Mol Gen Genet 170:25–242Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • James S. Backer
    • 1
  • C. William BirkyJr.
    • 2
  1. 1.Department of MedicineThe University of ChicagoChicagoUSA
  2. 2.Department of GeneticsThe Ohio State UniversityColumbusUSA

Personalised recommendations