Patterns of Naturally Occurring Restriction Map Variation, Dopa Decarboxylase Activity Variation and Linkage Disequilibrium in the Ddc Gene Region of Drosophila Melanogaster (original) (raw)

Abstract

Forty-six second-chromosome lines of Drosophila melanogaster isolated from five natural populations were surveyed for restriction map variation in a 65-kb region surrounding the gene (Ddc) encoding dopa decarboxylase (DDC). Sixty-nine restriction sites were scored, 13 of which were polymorphic. Average heterozygosity per nucleotide was estimated to be 0.005. Eight large (0.7-5.0 kb) inserts, two small inserts (100 and 200 bp) and three small deletions (100-300 bp) were also observed across the 65-kb region. We see no evidence for a reduction in either nucleotide heterozygosity or insertion/deletion variation in the central 26-kb segment containing Ddc and a dense cluster of lethal complementation groups and transcripts (>/=9 genes) compared to that seen in the adjacent regions (totaling 39 kb) in which only a single gene and transcript has been detected, or to that observed for other gene regions in D. melanogaster. The distribution of restriction site variation shows no significant departure from that expected under an equilibrium neutral model. However insertions and deletions show a significant departure from neutrality in that they are too rare in frequency, consistent with them being deleterious on average. Significant linkage disequilibrium among variants exists across much of the 65-kb region. Lower regional rates of recombination combined with the influence of polymorphic chromosomal inversions, rather than epistatic selection among genes in the dense cluster, probably are sufficient explanations for the creation and/or maintenance of the linkage disequilibrium observed in the Ddc region. We have also assayed adult DDC enzyme activity in these same lines. Twofold variation in activity among lines is observed within our sample. Significant associations are observed between level of DDC enzyme activity and restriction map variants. Surprisingly, one line with a 5.0-kb insert within an intron and one line with a 1.5-kb insert near the 5' end of Ddc each show normal adult DDC activities.

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Selected References

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  1. 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]
  2. Aquadro C. F., Tachida H., Langley C. H., Harada K., Mukai T. Increased variation in ADH enzyme activity in Drosophila mutation-accumulation experiment is not due to transposable elements at the Adh structural gene. Genetics. 1990 Dec;126(4):915–919. doi: 10.1093/genetics/126.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beech R. N., Brown A. J. Insertion-deletion variation at the yellow-achaete-scute region in two natural populations of Drosophila melanogaster. Genet Res. 1989 Feb;53(1):7–15. doi: 10.1017/s0016672300027804. [DOI] [PubMed] [Google Scholar]
  4. Begun D. J., Aquadro C. F. Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature. 1992 Apr 9;356(6369):519–520. doi: 10.1038/356519a0. [DOI] [PubMed] [Google Scholar]
  5. Begun D. J., Aquadro C. F. Molecular population genetics of the distal portion of the X chromosome in Drosophila: evidence for genetic hitchhiking of the yellow-achaete region. Genetics. 1991 Dec;129(4):1147–1158. doi: 10.1093/genetics/129.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bingham P. M., Levis R., Rubin G. M. Cloning of DNA sequences from the white locus of D. melanogaster by a novel and general method. Cell. 1981 Sep;25(3):693–704. doi: 10.1016/0092-8674(81)90176-8. [DOI] [PubMed] [Google Scholar]
  7. Charlesworth B., Langley C. H. The population genetics of Drosophila transposable elements. Annu Rev Genet. 1989;23:251–287. doi: 10.1146/annurev.ge.23.120189.001343. [DOI] [PubMed] [Google Scholar]
  8. Eanes W. F., Ajioka J. W., Hey J., Wesley C. Restriction-map variation associated with the G6PD polymorphism in natural populations of Drosophila melanogaster. Mol Biol Evol. 1989 Jul;6(4):384–397. doi: 10.1093/oxfordjournals.molbev.a040555. [DOI] [PubMed] [Google Scholar]
  9. Eanes W. F., Labate J., Ajioka J. W. Restriction-map variation with the yellow-achaete-scute region in five populations of Drosophila melanogaster. Mol Biol Evol. 1989 Sep;6(5):492–502. doi: 10.1093/oxfordjournals.molbev.a040565. [DOI] [PubMed] [Google Scholar]
  10. Eveleth D. D., Marsh J. L. Overlapping transcription units in Drosophila: sequence and structure of the Cs gene. Mol Gen Genet. 1987 Sep;209(2):290–298. doi: 10.1007/BF00329656. [DOI] [PubMed] [Google Scholar]
  11. Game A. Y., Oakeshott J. G. Associations between restriction site polymorphism and enzyme activity variation for esterase 6 in Drosophila melanogaster. Genetics. 1990 Dec;126(4):1021–1031. doi: 10.1093/genetics/126.4.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gilbert D., Hirsh J., Wright T. R. Molecular mapping of a gene cluster flanking the Drosophila Dopa decarboxylase gene. Genetics. 1984 Apr;106(4):679–694. doi: 10.1093/genetics/106.4.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Golding G. B., Aquadro C. F., Langley C. H. Sequence evolution within populations under multiple types of mutation. Proc Natl Acad Sci U S A. 1986 Jan;83(2):427–431. doi: 10.1073/pnas.83.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kojima K., Gillespie J., Toari Y. N. A profile of Drosophila species' enzymes assayed by electrophoresis. I. Number of alleles, heterozygosities, and linkage disequilibrium in glucose-metabolizing systems and some other enzymes. Biochem Genet. 1970 Oct;4(5):627–637. doi: 10.1007/BF00486100. [DOI] [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Langley C. H., Aquadro C. F. Restriction-map variation in natural populations of Drosophila melanogaster: white-locus region. Mol Biol Evol. 1987 Nov;4(6):651–663. doi: 10.1093/oxfordjournals.molbev.a040467. [DOI] [PubMed] [Google Scholar]
  17. Langley C. H., Shrimpton A. E., Yamazaki T., Miyashita N., Matsuo Y., Aquadro C. F. Naturally occurring variation in the restriction map of the amy region of Drosophila melanogaster. Genetics. 1988 Jul;119(3):619–629. doi: 10.1093/genetics/119.3.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Langley C. H., Tobari Y. N., Kojima K. I. Linkage disequilibrium in natural populations of Drosophila melanogaster. Genetics. 1974 Nov;78(3):921–936. doi: 10.1093/genetics/78.3.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Laurie-Ahlberg C. C., Maroni G., Bewley G. C., Lucchesi J. C., Weir B. S. Quantitative genetic variation of enzyme activities in natural populations of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1073–1077. doi: 10.1073/pnas.77.2.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Macpherson J. N., Weir B. S., Leigh Brown A. J. Extensive linkage disequilibrium in the achaete-scute complex of Drosophila melanogaster. Genetics. 1990 Sep;126(1):121–129. doi: 10.1093/genetics/126.1.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McCaman M. W., McCaman R. E., Lees G. J. Liquid cation exchange--a basis for sensitive radiometric assays for aromatic amino acid decarboxylases. Anal Biochem. 1972 Jan;45(1):242–252. doi: 10.1016/0003-2697(72)90024-3. [DOI] [PubMed] [Google Scholar]
  22. Miyashita N., Langley C. H. Molecular and phenotypic variation of the white locus region in Drosophila melanogaster. Genetics. 1988 Sep;120(1):199–212. doi: 10.1093/genetics/120.1.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nei M., Li W. H. Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5269–5273. doi: 10.1073/pnas.76.10.5269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Schaeffer S. W., Aquadro C. F., Langley C. H. Restriction-map variation in the Notch region of Drosophila melanogaster. Mol Biol Evol. 1988 Jan;5(1):30–40. doi: 10.1093/oxfordjournals.molbev.a040475. [DOI] [PubMed] [Google Scholar]
  26. Spencer C. A., Gietz R. D., Hodgetts R. B. Overlapping transcription units in the dopa decarboxylase region of Drosophila. Nature. 1986 Jul 17;322(6076):279–281. doi: 10.1038/322279a0. [DOI] [PubMed] [Google Scholar]
  27. Tachida H., Harada K., Langley C. H., Aquadro C. F., Yamazaki T., Cockerham C. C., Mukai T. Restriction map and alpha-amylase activity variation among Drosophila mutation accumulation lines. Genet Res. 1989 Dec;54(3):197–203. doi: 10.1017/s0016672300028652. [DOI] [PubMed] [Google Scholar]
  28. Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. doi: 10.1093/genetics/123.3.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Takano T. S., Kusakabe S., Mukai T. The genetic structure of natural populations of Drosophila melanogaster. XXII. Comparative study of DNA polymorphisms in northern and southern natural populations. Genetics. 1991 Nov;129(3):753–761. doi: 10.1093/genetics/129.3.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wright T. R. The genetic and molecular organization of the dense cluster of functionally related, vital genes in the DOPA decarboxylase region of the Drosophila melanogaster genome. Results Probl Cell Differ. 1987;14:95–120. doi: 10.1007/978-3-540-47783-9_7. [DOI] [PubMed] [Google Scholar]