Abstract
The alcohol dehydrogenase (Adh) locus (ADH; alcohol: NAD+ oxidoreductase, EC 1.1.1.1) of Drosophila pseudoobscura was cloned and sequenced. Forty-five percent of the "effectively silent sites" have changed between Adh in D. pseudoobscura of the obscura species group and the homologous DNA sequence in D. mauritiana , the latter representing the melanogaster species group. The untranslated leader sequence of the adult transcript of D. pseudoobscura has two deletions relative to the D. mauritiana message. The ADH protein sequences of D. pseudoobscura is missing the third and fourth amino acids at the N-terminus relative to the D. mauritiana enzyme. Of the remaining 254 amino acid positions, 27 (10.64%) differ between the two species. Amino acid replacements are randomly distributed into hydrophilic and hydrophobic domains of ADH. However, replacement substitutions are distributed nonrandomly across the three exons among D. pseudoobscura and members of the melanogaster subgroup, suggesting that functional constraints across the exons are different. Surprisingly, silent substitutions are also nonrandomly distributed with the third exon being the most divergent. This pattern suggests possible selective constraints on supposedly neutral silent substitutions and/or variation in underlying mutation rates across the gene. The presence of transcriptional and translational signals at the beginning and end of conserved sequences 3' to Adh implies the existence of a previously undescribed gene. Codon usage and patterns of nucleotide divergence are consistent with a protein coding function for this gene. In addition, conservation of nucleotide and amino acid sequence and similarity in hydropathy plots suggests that the gene 3' to Adh represents an ancient duplication of the Adh gene.
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- Aquadro C. F., Desse S. F., Bland M. M., Langley C. H., Laurie-Ahlberg C. C. Molecular population genetics of the alcohol dehydrogenase gene region of Drosophila melanogaster. Genetics. 1986 Dec;114(4):1165–1190. doi: 10.1093/genetics/114.4.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benyajati C., Spoerel N., Haymerle H., Ashburner M. The messenger RNA for alcohol dehydrogenase in Drosophila melanogaster differs in its 5' end in different developmental stages. Cell. 1983 May;33(1):125–133. doi: 10.1016/0092-8674(83)90341-0. [DOI] [PubMed] [Google Scholar]
- Chambers G. K., McDonald J. F., McElfresh M., Ayala F. J. Alcohol-oxidizing enzymes in 13 Drosophila species. Biochem Genet. 1978 Aug;16(7-8):757–767. doi: 10.1007/BF00484733. [DOI] [PubMed] [Google Scholar]
- Chia W., Karp R., McGill S., Ashburner M. Molecular analysis of the Adh region of the genome of Drosophila melanogaster. J Mol Biol. 1985 Dec 20;186(4):689–706. doi: 10.1016/0022-2836(85)90389-4. [DOI] [PubMed] [Google Scholar]
- Cohn V. H., Thompson M. A., Moore G. P. Nucleotide sequence comparison of the Adh gene in three drosophilids. J Mol Evol. 1984;20(1):31–37. doi: 10.1007/BF02101983. [DOI] [PubMed] [Google Scholar]
- Flavell A. J., Ruby S. W., Toole J. J., Roberts B. E., Rubin G. M. Translation and developmental regulation of RNA encoded by the eukaryotic transposable element copia. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7107–7111. doi: 10.1073/pnas.77.12.7107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayashida H., Miyata T. Unusual evolutionary conservation and frequent DNA segment exchange in class I genes of the major histocompatibility complex. Proc Natl Acad Sci U S A. 1983 May;80(9):2671–2675. doi: 10.1073/pnas.80.9.2671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
- Langer P. R., Waldrop A. A., Ward D. C. Enzymatic synthesis of biotin-labeled polynucleotides: novel nucleic acid affinity probes. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6633–6637. doi: 10.1073/pnas.78.11.6633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Langley C. H., Montgomery E., Quattlebaum W. F. Restriction map variation in the Adh region of Drosophila. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5631–5635. doi: 10.1073/pnas.79.18.5631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
- McDonell M. W., Simon M. N., Studier F. W. Analysis of restriction fragments of T7 DNA and determination of molecular weights by electrophoresis in neutral and alkaline gels. J Mol Biol. 1977 Feb 15;110(1):119–146. doi: 10.1016/s0022-2836(77)80102-2. [DOI] [PubMed] [Google Scholar]
- Needleman S. B., Wunsch C. D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443–453. doi: 10.1016/0022-2836(70)90057-4. [DOI] [PubMed] [Google Scholar]
- Pustell J., Kafatos F. C. A convenient and adaptable microcomputer environment for DNA and protein sequence manipulation and analysis. Nucleic Acids Res. 1986 Jan 10;14(1):479–488. doi: 10.1093/nar/14.1.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schaeffer S. W., Aquadro C. F., Anderson W. W. Restriction-map variation in the alcohol dehydrogenase region of Drosophila pseudoobscura. Mol Biol Evol. 1987 May;4(3):254–265. doi: 10.1093/oxfordjournals.molbev.a040438. [DOI] [PubMed] [Google Scholar]
- Smith J. M., Haigh J. The hitch-hiking effect of a favourable gene. Genet Res. 1974 Feb;23(1):23–35. [PubMed] [Google Scholar]
- Strobeck C. Expected linkage disequilibrium for a neutral locus linked to a chromosomal arrangement. Genetics. 1983 Mar;103(3):545–555. doi: 10.1093/genetics/103.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sturtevant A H, Novitski E. The Homologies of the Chromosome Elements in the Genus Drosophila. Genetics. 1941 Sep;26(5):517–541. doi: 10.1093/genetics/26.5.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wickens M., Stephenson P. Role of the conserved AAUAAA sequence: four AAUAAA point mutants prevent messenger RNA 3' end formation. Science. 1984 Nov 30;226(4678):1045–1051. doi: 10.1126/science.6208611. [DOI] [PubMed] [Google Scholar]
