Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2002 Oct;162(2):785–797. doi: 10.1093/genetics/162.2.785

Nucleotide polymorphism in the Est6 promoter, which is widespread in derived populations of Drosophila melanogaster, changes the level of Esterase 6 expressed in the male ejaculatory duct.

Wendy A Odgers 1, Charles F Aquadro 1, Christopher W Coppin 1, Marion J Healy 1, John G Oakeshott 1
PMCID: PMC1462297  PMID: 12399389

Abstract

Previous analysis of an Australian population of D. melanogaster revealed two predominant Est6 promoter haplotypes, P1 and P7. These haplotypes, which differ at 14 sites over a 325-bp region, are associated with a 15-20% difference in male EST6 activity. Here we show that the P1/P7 sequence difference causes the male activity variation by recreating the activity difference among >60 independently transformed lines containing representative P1 or P7 promoter alleles fused to an identical Est6 coding region. Furthermore we find that the whole fly difference reflects about a twofold difference in EST6 activity in the anterior sperm ejaculatory duct. EST6 activity variation in this tissue is known to affect reproductive fitness. Using a combination of RFLP analysis and DNA sequencing, we show that P1 and P7 are predominant in six populations from America, Asia, and Australia, albeit less frequent in a population from the presumptively ancestral east African range of the species. The sequence data show significant departures from neutral expectations for the derived American and Australian populations but not the presumptively ancestral Zimbabwean population. Thus the P1/P7 difference could be a major source of adaptively significant EST6 activity variation through much of the now cosmopolitan range of D. melanogaster.

Full Text

The Full Text of this article is available as a PDF (282.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguadé M. Positive selection drives the evolution of the Acp29AB accessory gland protein in Drosophila. Genetics. 1999 Jun;152(2):543–551. doi: 10.1093/genetics/152.2.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andolfatto P. Contrasting patterns of X-linked and autosomal nucleotide variation in Drosophila melanogaster and Drosophila simulans. Mol Biol Evol. 2001 Mar;18(3):279–290. doi: 10.1093/oxfordjournals.molbev.a003804. [DOI] [PubMed] [Google Scholar]
  3. Andolfatto P., Kreitman M. Molecular variation at the In(2L)t proximal breakpoint site in natural populations of Drosophila melanogaster and D. simulans. Genetics. 2000 Apr;154(4):1681–1691. doi: 10.1093/genetics/154.4.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Andolfatto P., Wall J. D., Kreitman M. Unusual haplotype structure at the proximal breakpoint of In(2L)t in a natural population of Drosophila melanogaster. Genetics. 1999 Nov;153(3):1297–1311. doi: 10.1093/genetics/153.3.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Balakirev E. S., Balakirev E. I., Rodríguez-Trelles F., Ayala F. J. Molecular evolution of two linked genes, Est-6 and Sod, in Drosophila melanogaster. Genetics. 1999 Nov;153(3):1357–1369. doi: 10.1093/genetics/153.3.1357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Begun D. J., Aquadro C. F. African and North American populations of Drosophila melanogaster are very different at the DNA level. Nature. 1993 Oct 7;365(6446):548–550. doi: 10.1038/365548a0. [DOI] [PubMed] [Google Scholar]
  7. Begun D. J., Aquadro C. F. Evolutionary inferences from DNA variation at the 6-phosphogluconate dehydrogenase locus in natural populations of drosophila: selection and geographic differentiation. Genetics. 1994 Jan;136(1):155–171. doi: 10.1093/genetics/136.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Begun D. J., Aquadro C. F. Molecular variation at the vermilion locus in geographically diverse populations of Drosophila melanogaster and D. simulans. Genetics. 1995 Jul;140(3):1019–1032. doi: 10.1093/genetics/140.3.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bénassi V., Aulard S., Mazeau S., Veuille M. Molecular variation of Adh and P6 genes in an African population of Drosophila melanogaster and its relation to chromosomal inversions. Genetics. 1993 Jul;134(3):789–799. doi: 10.1093/genetics/134.3.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bénassi V., Veuille M. Comparative population structuring of molecular and allozyme variation of Drosophila melanogaster Adh between Europe, west Africa and east Africa. Genet Res. 1995 Apr;65(2):95–103. doi: 10.1017/s0016672300033115. [DOI] [PubMed] [Google Scholar]
  11. Choudhary M., Laurie C. C. Use of in vitro mutagenesis to analyze the molecular basis of the difference in Adh expression associated with the allozyme polymorphism in Drosophila melanogaster. Genetics. 1991 Oct;129(2):481–488. doi: 10.1093/genetics/129.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cochrane B. J., Richmond R. C. Studies of esterase-6 in Drosophila melanogaster. II. The genetics and frequency distributions of naturally occurring variants studied by electrophoretic and heat stability criteria. Genetics. 1979 Oct;93(2):461–478. doi: 10.1093/genetics/93.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Collet C., Nielsen K. M., Russell R. J., Karl M., Oakeshott J. G., Richmond R. C. Molecular analysis of duplicated esterase genes in Drosophila melanogaster. Mol Biol Evol. 1990 Jan;7(1):9–28. doi: 10.1093/oxfordjournals.molbev.a040582. [DOI] [PubMed] [Google Scholar]
  14. Cooke P. H., Oakeshott J. G. Amino acid polymorphisms for esterase-6 in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1426–1430. doi: 10.1073/pnas.86.4.1426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. David J. R., Capy P. Genetic variation of Drosophila melanogaster natural populations. Trends Genet. 1988 Apr;4(4):106–111. doi: 10.1016/0168-9525(88)90098-4. [DOI] [PubMed] [Google Scholar]
  16. Dumancic M. M., Oakeshott J. G., Russell R. J., Healy M. J. Characterization of the EstP protein in Drosophila melanogaster and its conservation in drosophilids. Biochem Genet. 1997 Aug;35(7-8):251–271. doi: 10.1023/a:1021897016276. [DOI] [PubMed] [Google Scholar]
  17. Eanes W. F., Kirchner M., Yoon J., Biermann C. H., Wang I. N., McCartney M. A., Verrelli B. C. Historical selection, amino acid polymorphism and lineage-specific divergence at the G6pd locus in Drosophila melanogaster and D. simulans. Genetics. 1996 Nov;144(3):1027–1041. doi: 10.1093/genetics/144.3.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fickett J. W., Wasserman W. W. Discovery and modeling of transcriptional regulatory regions. Curr Opin Biotechnol. 2000 Feb;11(1):19–24. doi: 10.1016/s0958-1669(99)00049-x. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Game A. Y., Oakeshott J. G. Variation in the amount and activity of esterase 6 in a natural population of Drosophila melanogaster. Heredity (Edinb) 1989 Feb;62(Pt 1):27–34. doi: 10.1038/hdy.1989.4. [DOI] [PubMed] [Google Scholar]
  21. Gilbert D. G., Richmond R. C. Esterase 6 in Drosophila melanogaster: reproductive function of active and null males at low temperature. Proc Natl Acad Sci U S A. 1982 May;79(9):2962–2966. doi: 10.1073/pnas.79.9.2962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gloor G. B., Preston C. R., Johnson-Schlitz D. M., Nassif N. A., Phillis R. W., Benz W. K., Robertson H. M., Engels W. R. Type I repressors of P element mobility. Genetics. 1993 Sep;135(1):81–95. doi: 10.1093/genetics/135.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hasson E., Eanes W. F. Contrasting histories of three gene regions associated with In(3L)Payne of Drosophila melanogaster. Genetics. 1996 Dec;144(4):1565–1575. doi: 10.1093/genetics/144.4.1565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Healy M. J., Dumancic M. M., Cao A., Oakeshott J. G. Localization of sequences regulating ancestral and acquired sites of esterase6 activity in Drosophila melanogaster. Mol Biol Evol. 1996 Jul;13(6):784–797. doi: 10.1093/oxfordjournals.molbev.a025639. [DOI] [PubMed] [Google Scholar]
  25. Inoue Y., Igarashi Y. On the category of naturally occurring inversions of Drosophila melanogaster. Jpn J Genet. 1994 Apr;69(2):105–118. doi: 10.1266/jjg.69.105. [DOI] [PubMed] [Google Scholar]
  26. Irvin S. D., Wetterstrand K. A., Hutter C. M., Aquadro C. F. Genetic variation and differentiation at microsatellite loci in Drosophila simulans. Evidence for founder effects in new world populations. Genetics. 1998 Oct;150(2):777–790. doi: 10.1093/genetics/150.2.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Karotam J., Delves A. C., Oakeshott J. G. Conservation and change in structural and 5' flanking sequences of esterase 6 in sibling Drosophila species. Genetica. 1993;88(1):11–28. doi: 10.1007/BF02424448. [DOI] [PubMed] [Google Scholar]
  28. Keplinger B. L., Guo X., Quine J., Feng Y., Cavener D. R. Complex organization of promoter and enhancer elements regulate the tissue- and developmental stage-specific expression of the Drosophila melanogaster Gld gene. Genetics. 2001 Feb;157(2):699–716. doi: 10.1093/genetics/157.2.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Labate J., Bortoli A., Game A. Y., Cooke P. H., Oakeshott J. G. The number and distribution of esterase 6 alleles in populations of Drosophila melanogaster. Heredity (Edinb) 1989 Oct;63(Pt 2):203–208. doi: 10.1038/hdy.1989.93. [DOI] [PubMed] [Google Scholar]
  30. Laurie-Ahlberg C. C., Stam L. F. Use of P-element-mediated transformation to identify the molecular basis of naturally occurring variants affecting Adh expression in Drosophila melanogaster. Genetics. 1987 Jan;115(1):129–140. doi: 10.1093/genetics/115.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Laurie C. C., Stam L. F. The effect of an intronic polymorphism on alcohol dehydrogenase expression in Drosophila melanogaster. Genetics. 1994 Oct;138(2):379–385. doi: 10.1093/genetics/138.2.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ludwig M. Z., Bergman C., Patel N. H., Kreitman M. Evidence for stabilizing selection in a eukaryotic enhancer element. Nature. 2000 Feb 3;403(6769):564–567. doi: 10.1038/35000615. [DOI] [PubMed] [Google Scholar]
  33. Myers M. A., Healy M. J., Oakeshott J. G. Mutational analysis of N-linked glycosylation of esterase 6 in Drosophila melanogaster. Biochem Genet. 1996 Jun;34(5-6):201–218. doi: 10.1007/BF02407020. [DOI] [PubMed] [Google Scholar]
  34. Oakeshott J. G., Chambers G. K., Gibson J. B., Willcocks D. A. Latitudinal relationships of esterase-6 and phosphoglucomutase gene frequencies in Drosophila melanogaster. Heredity (Edinb) 1981 Dec;47(Pt 3):385–396. doi: 10.1038/hdy.1981.99. [DOI] [PubMed] [Google Scholar]
  35. Oakeshott J. G., van Papenrecht E. A., Claudianos C., Morrish B. C., Coppin C., Odgers W. A. An episode of accelerated amino acid change in Drosophila esterase-6 associated with a change in physiological function. Genetica. 2000;110(3):231–244. doi: 10.1023/a:1012727814167. [DOI] [PubMed] [Google Scholar]
  36. Odgers W. A., Healy M. J., Oakeshott J. G. Nucleotide polymorphism in the 5' promoter region of esterase 6 in Drosophila melanogaster and its relationship to enzyme activity variation. Genetics. 1995 Sep;141(1):215–222. doi: 10.1093/genetics/141.1.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Richmond R. C., Gilbert D. G., Sheehan K. B., Gromko M. H., Butterworth F. M. Esterase 6 and reproduction in Drosophila melanogaster. Science. 1980 Mar 28;207(4438):1483–1485. doi: 10.1126/science.6767273. [DOI] [PubMed] [Google Scholar]
  38. Robertson H. M., Preston C. R., Phillis R. W., Johnson-Schlitz D. M., Benz W. K., Engels W. R. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics. 1988 Mar;118(3):461–470. doi: 10.1093/genetics/118.3.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rozas J., Rozas R. DnaSP version 3: an integrated program for molecular population genetics and molecular evolution analysis. Bioinformatics. 1999 Feb;15(2):174–175. doi: 10.1093/bioinformatics/15.2.174. [DOI] [PubMed] [Google Scholar]
  40. Saad M., Game A. Y., Healy M. J., Oakeshott J. G. Associations of esterase 6 allozyme and activity variation with reproductive fitness in Drosophila melanogaster. Genetica. 1994;94(1):43–56. doi: 10.1007/BF01429219. [DOI] [PubMed] [Google Scholar]
  41. Schlötterer C., Vogl C., Tautz D. Polymorphism and locus-specific effects on polymorphism at microsatellite loci in natural Drosophila melanogaster populations. Genetics. 1997 May;146(1):309–320. doi: 10.1093/genetics/146.1.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Voelker R. A., Langley C. H., Brown A. J., Ohnishi S., Dickson B., Montgomery E., Smith S. C. Enzyme null alleles in natural populations of Drosophila melanogaster: Frequencies in a North Carolina population. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1091–1095. doi: 10.1073/pnas.77.2.1091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Yuh C. H., Bolouri H., Davidson E. H. Genomic cis-regulatory logic: experimental and computational analysis of a sea urchin gene. Science. 1998 Mar 20;279(5358):1896–1902. doi: 10.1126/science.279.5358.1896. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES