Abstract
An alcohol dehydrogenase null activity allele,Adh nAH52, extracted from a natural population ofDrosophila melanogaster has been cloned and sequenced. Compared with the wild-type consensus sequence, the nucleotide sequence ofAdh nAH52 contains eight extra bases in intron 2, adjacent to the 5' splice site. It seems likely that the extra bases result from two structural changes, with a 10-base pair insertion at the same site as a 2-base pair deletion. The insertion includes an 8-base pair duplication of an adjoining region. This structural change alters transcription to give rise to an mRNA which is longer than normal and at 10% of the wild-type level.
Similar content being viewed by others
References
Aaron, C. S. (1979). X-ray induced mutations affecting the level of the enzyme alcohol dehydrogenase inDrosophila melanogaster: Frequency and genetic analysis of the null enzyme mutants.Mutat. Res. 63127.
Aebi, M., and Weissmann, C. (1987). Precision and orderliness in splicing.Trends Genet. 3102.
Batzer, M. A., Tedeschi, B., Fossett, N. G., Tucker, A., Kilroy, G., Arbour, P., and Lee, W. R. (1988). Spectra of molecular changes induced in DNA ofDrosophila spermatozoa by 1-ethyl-1-nitrosourea and X-rays.Mutat. Res. 199255.
Benyajati, C., Place, A. R., Wang, N., Pentz, E., and Sofer, W. (1982). Deletions at intervening sequence splice sites in the alcohol dehydrogenase gene ofDrosophila.Nucleic Acids Res. 107261.
Benyajati, C., Spoerel, N., Haymerle, H., and Ashburner, M. (1983a). The messenger RNA for alcohol dehydrogenase inDrosophila melanogaster differs in its 5′ end in different developmental stages.Cell 33125.
Benyajati, C., Place, A. R., and Sofer, W. (1983b). Formaldehyde mutagenesis inDrosophila: Molecular analysis of ADH-negative mutants.Mutat. Res. 1111.
Brawerman, G. (1987). Determinants of messenger RNA stability.Cell 485.
Chia, W., Savakis, C., Karp, R., Pelham, H., and Ashburner, M. (1985). Mutation of theAdh gene ofDrosophila melanogaster containing an internal tandem duplication.J. Mol. Biol. 186679.
Chia, W., Savakis, C., Karp, R., and Ashburner, M. (1987).Adh n4 ofDrosophila melanogaster is a nonsense mutation.Nucleic Acids Res. 153931.
David, J. R., Bocquet, C., Arens, M. F., and Fouillet, P. (1976). Biological role of alcohol dehydrogenase in the tolerance ofDrosophila melanogaster to aliphatic alcohols: Utilization of an ADH-null mutant.Biochem. Genet. 14989.
Finnegan, P. J., and Fawcett, D. H. (1985). Transposable elements inDrosophila melanogaster. In Maclean, N. (ed.),Oxford Surveys on Eukaryotic Genes, Vol. 3 OUP, Oxford.
Freeth, A. L., and Gibson, J. B. (1985). Alcohol dehydrogenase and sn glycerol-3-phosphate dehydrogenase null activity alleles in natural populations ofDrosophila melanogaster.Heredity 55369.
Freeth, A. L., Gibson, J. B., and de Couet, H. G. (1986). The partial characterization of alcohol dehydrogenase null alleles from natural populations ofDrosophila melanogaster.Biochem. Genet. 24957.
Freeth, A. L., Gibson, J. B., and Wilks, A. V. (1988). Transcription analysis of alcohol dehydrogenase null alleles from natural populations ofDrosophila melanogaster.Genome 3025.
Frischauf, A. M., Lehrach, H., Pouska, A., and Murray, N. (1983). Lambda replacement vectors carrying polylinker sequences.J. Mol. Biol. 170827.
Fukumaki, Y., Ghosh, P. K., Benz, E. J., Jr., Reddy, V. B., Lebowitz, P., Forget, B. G., and Weissman, S. M. (1982). Abnormally spliced messenger RNA in erythroid cells from patients with beta+ thalassemia and monkey cells expressing a cloned beta+-thalassemic gene.Cell 28585.
Geer, B. W., Langevin, M. L., and McKecknie, S. W. (1985). Dietary ethanol and lipid synthesis inDrosophila melanogaster.Biochem. Genet. 23607.
Gibson, J. B., and Wilks, A. V. (1988). The alcohol dehydrogenase polymorphism ofDrosophila melanogaster in relation to environmental ethanol, ethanol tolerance and alcohol dehydrogenase activity.Heredity 60403.
Goldberg, D. A. (1980). Isolation and partial characterization of theDrosophila alcohol dehydrogenase gene.Proc. Natl. Acad. Sci. USA 775794.
Green, M. R. (1986). Pre-mRNA splicing.Annu. Rev. Genet. 170671.
Grell, E. H., Jacobson, K. B., and Murphy, J. B. (1968). Alterations of genetic material for analysis of alcohol dehydrogenase ofDrosophila melanogaster.Ann. N.Y. Acad. Sci. 151441.
Henikoff, S. (1983). Cloning exons for mapping of transcription: Characterisation of theDrosophila melanogaster alcohol dehydrogenase gene.Nucleic Acids Res. 114735.
Jacob, M., and Gallinaro, H. (1989). The 5′ splice site: Phylogenetic evolution and variable geometry of association with U1RNA.Nucleic Acids Res. 172159.
Jiang, C., Gibson, J. B., Wilks, A. V., and Freeth, A. L. (1988). Restriction endonuclease variation in the region of the alcohol dehydrogenase gene: A comparison of null and normal alleles from natural populations ofDrosophila melanogaster.Heredity 60101.
Kelly, M. R., Mims, I. P., Farnet, C. M., Dicharry, S. A., and Lee, W. R. (1985). Molecular analysis of X-ray induced alcohol dehydrogenase (ADH) null mutations in Drosophila melanogaster.Genetics 109365.
Kreitman, M. (1983). Nucleotide polymorphism at the alcohol dehydrogenase locus ofDrosophila melanogaster.Nature 304412.
Langley, C. H., Voelker, R. A., Leigh Brown, A. J., Ohnishi, S., Dickson, B., and Montgomery, E. (1981). Null allele frequencies at allozyme loci in natural populations ofDrosophila melanogaster.Genetics 99151.
Levinson, G., and Gutman, G. A. (1987). Slipped-strand mispairing: A major mechanism for DNA sequence evolution.Mol. Biol. Evol. 4(3):203.
Lindsley, D. L., and Grell, E. H. (1968). Genetic variations ofDrosophila melanogaster. Carnegie Inst. Wash. Publ. No. 627.
Martin, P. F., Place, A. R., Pentz, E., and Sofer, W. (1985). UGA nonsense mutation in the alcohol dehydrogenase gene ofDrosophila melanogaster.J. Mol. Biol. 184221.
Middleton, R. J., and Kacser, H. (1983). Enzyme variation, metabolic flux and fitness: Alcohol dehydrogenase inDrosophila melanogaster.Genetics 105633.
O'Donnell, J., Mandel, H. C., Krauss, M., and Sofer, W. (1977). Genetic and cytogenetic analysis of the ADH region inDrosophila melanogaster.Genetics 86553.
Roiha, H., Rubin, G., and O'Hare, K. (1988). P element insertions and rearrangements at the singed locus ofDrosophila melanogaster.Genetics 11975.
Savakis, C., Ashburner, M., and Willis, J. H. (1986). The expression of the gene coding for alcohol dehydrogenase during the development ofDrosophila melanogaster.Dev. Biol. 114194.
Searles, L. L., Scott, J. R., Bingham, P. M., Voelker, R. A., and Greenleaf, A. L. (1982). Molecular cloning of sequences from aDrosophila RNA polymerase II locus by P element transposon tagging.Cell 31585.
Sharp, P. A. (1987). Splicing of messenger RNA precursors.Science 235766.
Sofer, W. H., and Hatkoff, M. A. (1972). Chemical selection of alcohol dehydrogenase negative mutants inDrosophila.Genetics 72545.
Streisinger, G., Okada, Y., Emrich, J., Newton, J., Tsugita, A., Terzhaghi, E., and Inouye, M. (1966). Frameshift mutations and the genetic code.Cold Spring Harbor Symp. Quant. Biol. 3177.
Thatcher, D. R. (1980). The complete amino acid sequence of three alcohol dehydrogenase alleloenzymes (Adh n11,Adh S andAdh UF) from the fruitflyDrosophila melanogaster.Biochem. J. 187875.
Truett, M. A., Jones, R. S., and Potter, S. S. (1981). Unusual structure of the FB family of transposable elements inDrosophila.Cell 24753.
Ursprung, H., Sofer, W. H., and Burroughs, N. (1970). Ontogeny and tissue distribution of alcohol dehydrogenase inDrosophila melanogaster.Wilhelm Roux Arch. 164201.
Van Delden, W. (1982). The alcohol dehydrogenase polymorphism inDrosophila melanogaster. Selection at an enzyme locus.Evol. Biol. 15187.
Voelker, R. A., Schaffer, H. E., and Mukai, T. (1980). Spontaneous allozyme mutations inDrosophila melanogaster: Rate of occurence and nature of the mutants.Genetics 94961.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gibson, J.B., Wilks, A.V. Molecular structure of a naturally occurring alcohol dehydrogenase null activity allele inDrosophila melanogaster . Biochem Genet 27, 679–688 (1989). https://doi.org/10.1007/BF02396060
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02396060