Original Article

Heredity (1997) 78, 1–11; doi:10.1038/hdy.1997.1

P-element inserts in transgenic flies: a cautionary tale

Marcel Kaiser1, Matthias Gasser1, Ruedi Ackermann2 and Stephen C Stearns1

  1. 1Zoology Institute, University of Basle, Rheinsprung 9, CH-4051 Basle
  2. 2Biocentre, University of Basle, Klingelbergstrasse 70, CH-4056 Basle, Switzerland

Correspondence: Stephen C Stearns, Zoology Institute, University of Basle, Rheinsprung 9, CH-4051 Basle. E-mail: stearns@wz.unibas.ch

Received 2 January 1996.



The fruitfly, Drosophila melanogaster, can be transfected with P-elements and induced to overexpress a transfected gene whose impact on lifespan can be measured. Here, it is reported that in previous experiments a transfected gene was not expressed. This suggested a new statistical analysis indicating that (1) the size of the insert, the position and the interactions of the insert with the genetic backgrounds into which the P-element are inserted have effects on lifespan similar to those attributed to overexpression; (2) these effects occur without expression of the transfected gene; and (3) effects of interactions with backgrounds and effects of positions are as large as responses to six generations of strong directional artificial selection. Reports of effects of overexpression of transfected genes on lifespan in Drosophila melanogaster may be experimental artefacts. Credible experiments on the phenotypic effects of trans-genesis need proper controls for the effects of insert size and position and should estimate the magnitudes of interactions of treatment with genetic backgrounds.


Drosophila melanogaster, elongation factor, genetic manipulation, lifespan, position effects, size effects



  1. Arking, R, and Clare, M. 1986. Genetics of aging: Effective selection for increased longevity in Drosophila. In: Collatz, K.-G. and Sohal, R. S. (eds) Insect Aging: Strategies and Mechanism, pp. 217–236. Springer Verlag, Berlin.
  2. Ashburner, M. 1989. Drosophila, pp. 1053–1054. Cold Spring Harbor Laboratory Press, New York.
  3. Bellen, H J, O'Kane, C J, Wilson, C, Grossniklaus, U, Pearson, R K, and Gehring, W J. 1989. P-element mediated enhancer detection: a versatile method to study development in Drosophila. Genes Devel, 3, 1288–1300.
  4. Chomczynski, P, and Sacchi, N. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analyt Biochem, 162, 156–159. | Article | PubMed | ISI | ChemPort |
  5. Finch, C E. 1990. Longevity, Senescence, and the Genome. University of Chicago Press, Chicago.
  6. Friedman, D B, and Johnson, T E. 1988a. A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics, 118, 75–86. | PubMed | ISI | ChemPort |
  7. Friedman, D B, and Johnson, T E. 1988b. Three mutants that extend both mean and maximum life span of the nematode, Caenorhabditis elegans, define the age-1 gene. J Gerontol, 43, B102–B109. | PubMed | ISI | ChemPort |
  8. Giller, T, Brunner, L, Pick, L, and Brack, C. 1987. A homologous in vitro system to analyse transcription of a mouse immunoglobulin mu heavy-chain gene. Eur J Biochem, 172, 679–685.
  9. Hazelrigg, T, Levis, R, and Rubin, G M. 1984. Transformation of white locus DNA in Drosophila: dosage compensation, zeste interaction and position effects. Cell, 36, 469–481. | Article | PubMed | ISI | ChemPort |
  10. Levenbook, L. 1986. Protein synthesis in relation to insect aging: An overview. In: Collatz, K.-G. and Sohal, R. S. (eds) Insect Aging: Strategies and Mechanism, pp. 200–206. Springer Verlag, Berlin.
  11. Lints, F A, and Bourgois, M. 1985. Aging and lifespan in insects with special regard to Drosophila: review 1982–84. Rev Biol Res Aging, 2, 61–84.
  12. Luckinbill, L S, Arking, R, Clare, M J, Cirocco, W C, and Buck, S A. 1984. Selection for delayed senescence in Drosophila melanogaster. Evolution, 38, 996–1003. | Article | ISI |
  13. Mackay, T F C. 1989. Transposable elements and fitness in Drosophila melanogaster. Genome, 31, 284–295.
  14. Mackay, T F C, Lyman, R F, and Jackson, M S. 1992. Effects of P element insertions on quantitative traits in Drosophila melanogaster. Genetics, 130, 315–332. | PubMed | ISI | ChemPort |
  15. Melton, D A, Krieg, P A, Rebagliati, M R, Maniatis, T, Zinn, K, and Green, M R. 1984. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucl Acids Res, 12, 7035–7056. | PubMed | ISI | ChemPort |
  16. Moldave, K. 1985. Eucaryotic protein synthesis. Ann Rev Biochem, 54, 1109–1149. | PubMed | ChemPort |
  17. Orr, W C, and Sohal, R S. 1992. The effects of catalase gene overexpression on life span and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch Biochem Biophys, 297, 35–41. | PubMed | ISI | ChemPort |
  18. Orr, W C, and Sohal, R S. 1993. Effect of Cu-Zn super oxide dismutase overexpression on life span and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch Biochem Biophys, 301, 34–40. | Article | PubMed | ISI | ChemPort |
  19. Orr, W C, and Sohal, R S. 1994. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science, 263, 1128–1130. | Article | PubMed | ISI | ChemPort |
  20. Riis, B, Rattan, S I S, Clark, B F C, and Merrick, W C. 1990. Eukaryotic protein elongation factors. Trends Biochem Sci, 15, 420–424. | Article | PubMed | ISI |
  21. Robertson, H M, Preston, C R, Phillis, R W, Johnsonschlitz, D W, Benz, W K, and Engels, W R. 1988. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics, 118, 461–470. | PubMed | ISI | ChemPort |
  22. Rose, M R. 1984. Laboratory evolution of postponed senescence in Drosophila melanogaster. Evolution, 38, 1004–1010. | Article | ISI |
  23. Rubin, G M, and Spradling, A C. 1982. Genetic transformation of Drosophila with transposable element vectors. Science, 218, 348–353. | Article | PubMed | ISI | ChemPort |
  24. Shepherd, J W C, Walldorf, U, Hug, P, and Gehring, W J. 1989. Fruit flies with additional expression of the elongation factor EF-1alpha live longer. Proc Natl Acad Sci USA, 86, 7520–7521.
  25. Shikama, N, Ackermann, R, and Brack, C. 1994. Protein synthesis elongation factor EF-1alpha expression and longevity in Drosophila melanogaster. Proc Natl Acad Sci USA, 91, 4199–4203. | Article | PubMed | ChemPort |
  26. Sokal, R R, and Rohlf, F J. 1981. Biometry, 2nd edn. W. H. Freeman, San Francisco.
  27. Stearns, S C, and Kaiser, M. 1993. The effects of enhanced expression of elongation factor EF-1alpha on lifespan in Drosophila melanogaster. IV. A summary of three experiments. Genetica, 91, 167–182.
  28. Stearns, S C, Diggelmann, T, Gebhardt, M, Bach-Mamm, H, and Wechsler, R. 1987. A device for collecting flies of precisely determined post-hatching age. Drosoph Inf Serv, 66, 167–169.
  29. Stearns, S C, Kaiser, M, and Hillesheim, E. 1993. Effect on fitness components of enhanced expression of elongation factor EF-1alpha in Drosophila melanogaster. I. The contrasting approaches of molecular and population biologists. Am Nat, 142, 961–993.
  30. Tatsuka, M, Mitsui, H, Wada, M, Nagata, A, Nojima, H, and Okayama, H. 1992. Elongation factor-1alpha gene determines susceptibility to transformation. Nature, 359, 333–336. | Article | PubMed | ISI | ChemPort |
  31. Wakimoto, B T, Kalfayan, L J, and Spradling, A C. 1986. Developmentally regulated expression of Drosophila chorion genes introduced at different chromosomal positions. J Mol Biol, 187, 33–45. | Article | PubMed | ISI | ChemPort |
  32. Webster, G C. 1985. Protein synthesis in aging organisms. In: Sohal, R. S., Birnbaum, L. S. and Cutler, R.G. (eds) Molecular Biology of Aging: Gene Stability and Gene Expression, pp. 263–289. Raven Press, New York.
  33. Webster, G C. 1986. Effect of aging on the components of the protein synthesis system. In: Collatz, K.-G. and Sohal, R. S. (eds) Insect Aging: Strategies and Mechanism, pp. 207–216. Springer Verlag, Berlin.
  34. Wilson, C, Bellen, H J, and Gehring, W J. 1990. Position effects on eukaryotic gene expression. Ann Rev Cell Biol, 6, 679–714. | PubMed |
  35. Zwaan, S. 1993. Genetical and environmental aspects of ageing in drosophila melanogaster: an evolutionary perspective. Phd thesis, university of groningen.