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. 1996 Nov;144(3):1027–1041. doi: 10.1093/genetics/144.3.1027

Historical Selection, Amino Acid Polymorphism and Lineage-Specific Divergence at the G6pd Locus in Drosophila Melanogaster and D. Simulans

W F Eanes 1, M Kirchner 1, J Yoon 1, C H Biermann 1, I N Wang 1, M A McCartney 1, B C Verrelli 1
PMCID: PMC1207599  PMID: 8913747

Abstract

The nucleotide diversity across 1705 bp of the G6pd gene is studied in 50 Drosophila melanogaster and 12 D. simulans lines. Our earlier report contrasted intraspecific polymorphism and interspecific differences at silent and replacement sites in these species. This report expands the number of European and African lines and examines the pattern of polymorphism with respect to the common A/B allozymes. In D. melanogaster the silent nucleotide diversity varies 2.8-fold across localities. The B allele sequences are two- to fourfold more variable than the derived A allele, and differences between allozymes are twice as among B alleles. There is strong linkage disequilibrium across the G6pd region. In both species the level of silent polymorphism increases from the 5' to 3' ends, while there is no comparable pattern in level of silent site divergence or fixation. The neutral model is not rejected in either species. Using D. yakuba as an outgroup, the D. melanogaster lineage shows a twofold greater rate of silent fixation, but less than half the rate of amino acid replacement. Lineage-specific differences in mutation fixation are inconsistent with neutral expectations and suggest the interaction of species-specific population size differences with both weakly advantageous and deleterious selection.

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Selected References

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  1. Aquadro C. F. Why is the genome variable? Insights from Drosophila. Trends Genet. 1992 Oct;8(10):355–362. doi: 10.1016/0168-9525(92)90281-8. [DOI] [PubMed] [Google Scholar]
  2. Ayala F. J., Hartl D. L. Molecular drift of the bride of sevenless (boss) gene in Drosophila. Mol Biol Evol. 1993 Sep;10(5):1030–1040. doi: 10.1093/oxfordjournals.molbev.a040052. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Cavener D. R., Clegg M. T. Evidence for biochemical and physiological differences between enzyme genotypes in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4444–4447. doi: 10.1073/pnas.78.7.4444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Charlesworth D., Charlesworth B., Morgan M. T. The pattern of neutral molecular variation under the background selection model. Genetics. 1995 Dec;141(4):1619–1632. doi: 10.1093/genetics/141.4.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Eanes W. F., Katona L., Longtine M. Comparison of in vitro and in vivo activities associated with the G6PD allozyme polymorphism in Drosophila melanogaster. Genetics. 1990 Aug;125(4):845–853. doi: 10.1093/genetics/125.4.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eanes W. F., Kirchner M., Taub D. R., Yoon J., Chen J. T. Amino acid polymorphism and rare electrophoretic variants of G6PD from natural populations of Drosophila melanogaster. Genetics. 1996 May;143(1):401–406. doi: 10.1093/genetics/143.1.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eanes W. F., Kirchner M., Yoon J. Evidence for adaptive evolution of the G6pd gene in the Drosophila melanogaster and Drosophila simulans lineages. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7475–7479. doi: 10.1073/pnas.90.16.7475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eanes W. F., Wesley C., Charlesworth B. Accumulation of P elements in minority inversions in natural populations of Drosophila melanogaster. Genet Res. 1992 Feb;59(1):1–9. doi: 10.1017/s0016672300030111. [DOI] [PubMed] [Google Scholar]
  12. Fouts D., Ganguly R., Gutierrez A. G., Lucchesi J. C., Manning J. E. Nucleotide sequence of the Drosophila glucose-6-phosphate dehydrogenase gene and comparison with the homologous human gene. Gene. 1988 Mar 31;63(2):261–275. doi: 10.1016/0378-1119(88)90530-6. [DOI] [PubMed] [Google Scholar]
  13. Fu Y. X., Li W. H. Statistical tests of neutrality of mutations. Genetics. 1993 Mar;133(3):693–709. doi: 10.1093/genetics/133.3.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ganguly R., Ganguly N., Manning J. E. Isolation and characterization of the glucose-6-phosphate dehydrogenase gene of Drosophila melanogaster. Gene. 1985;35(1-2):91–101. doi: 10.1016/0378-1119(85)90161-1. [DOI] [PubMed] [Google Scholar]
  15. Gillespie J. H., Langley C. H. Are evolutionary rates really variable? J Mol Evol. 1979 Jun 8;13(1):27–34. doi: 10.1007/BF01732751. [DOI] [PubMed] [Google Scholar]
  16. Gillespie J. H. Substitution processes in molecular evolution. III. Deleterious alleles. Genetics. 1994 Nov;138(3):943–952. doi: 10.1093/genetics/138.3.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hey J., Kliman R. M. Population genetics and phylogenetics of DNA sequence variation at multiple loci within the Drosophila melanogaster species complex. Mol Biol Evol. 1993 Jul;10(4):804–822. doi: 10.1093/oxfordjournals.molbev.a040044. [DOI] [PubMed] [Google Scholar]
  18. Higuchi R. G., Ochman H. Production of single-stranded DNA templates by exonuclease digestion following the polymerase chain reaction. Nucleic Acids Res. 1989 Jul 25;17(14):5865–5865. doi: 10.1093/nar/17.14.5865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hill W. G. Estimation of linkage disequilibrium in randomly mating populations. Heredity (Edinb) 1974 Oct;33(2):229–239. doi: 10.1038/hdy.1974.89. [DOI] [PubMed] [Google Scholar]
  20. Hudson R. R. Estimating the recombination parameter of a finite population model without selection. Genet Res. 1987 Dec;50(3):245–250. doi: 10.1017/s0016672300023776. [DOI] [PubMed] [Google Scholar]
  21. Hudson R. R., Kaplan N. L. Deleterious background selection with recombination. Genetics. 1995 Dec;141(4):1605–1617. doi: 10.1093/genetics/141.4.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hudson R. R., Kaplan N. L. On the divergence of alleles in nested subsamples from finite populations. Genetics. 1986 Aug;113(4):1057–1076. doi: 10.1093/genetics/113.4.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hudson R. R., Kaplan N. L. The coalescent process in models with selection and recombination. Genetics. 1988 Nov;120(3):831–840. doi: 10.1093/genetics/120.3.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hudson R. R., Kreitman M., Aguadé M. A test of neutral molecular evolution based on nucleotide data. Genetics. 1987 May;116(1):153–159. doi: 10.1093/genetics/116.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jeffs P. S., Holmes E. C., Ashburner M. The molecular evolution of the alcohol dehydrogenase and alcohol dehydrogenase-related genes in the Drosophila melanogaster species subgroup. Mol Biol Evol. 1994 Mar;11(2):287–304. doi: 10.1093/oxfordjournals.molbev.a040110. [DOI] [PubMed] [Google Scholar]
  26. Kaplan N. L., Darden T., Hudson R. R. The coalescent process in models with selection. Genetics. 1988 Nov;120(3):819–829. doi: 10.1093/genetics/120.3.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kaplan N. L., Hudson R. R., Langley C. H. The "hitchhiking effect" revisited. Genetics. 1989 Dec;123(4):887–899. doi: 10.1093/genetics/123.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kimura M. Model of effectively neutral mutations in which selective constraint is incorporated. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3440–3444. doi: 10.1073/pnas.76.7.3440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kimura M. The number of heterozygous nucleotide sites maintained in a finite population due to steady flux of mutations. Genetics. 1969 Apr;61(4):893–903. doi: 10.1093/genetics/61.4.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kreitman M. E., Aguadé M. Excess polymorphism at the Adh locus in Drosophila melanogaster. Genetics. 1986 Sep;114(1):93–110. doi: 10.1093/genetics/114.1.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kreitman M., Hudson R. R. Inferring the evolutionary histories of the Adh and Adh-dup loci in Drosophila melanogaster from patterns of polymorphism and divergence. Genetics. 1991 Mar;127(3):565–582. doi: 10.1093/genetics/127.3.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kreitman M. Nucleotide polymorphism at the alcohol dehydrogenase locus of Drosophila melanogaster. Nature. 1983 Aug 4;304(5925):412–417. doi: 10.1038/304412a0. [DOI] [PubMed] [Google Scholar]
  33. Labate J., Eanes W. F. Direct measurement of in vivo flux differences between electrophoretic variants of G6PD from Drosophila melanogaster. Genetics. 1992 Nov;132(3):783–787. doi: 10.1093/genetics/132.3.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Langley C. H., Fitch W. M. An examination of the constancy of the rate of molecular evolution. J Mol Evol. 1974;3(3):161–177. doi: 10.1007/BF01797451. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Leicht B. G., Muse S. V., Hanczyc M., Clark A. G. Constraints on intron evolution in the gene encoding the myosin alkali light chain in Drosophila. Genetics. 1995 Jan;139(1):299–308. doi: 10.1093/genetics/139.1.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Lewontin R. C. The detection of linkage disequilibrium in molecular sequence data. Genetics. 1995 May;140(1):377–388. doi: 10.1093/genetics/140.1.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. McDonald J. H., Kreitman M. Adaptive protein evolution at the Adh locus in Drosophila. Nature. 1991 Jun 20;351(6328):652–654. doi: 10.1038/351652a0. [DOI] [PubMed] [Google Scholar]
  39. McGinnis W., Shermoen A. W., Beckendorf S. K. A transposable element inserted just 5' to a Drosophila glue protein gene alters gene expression and chromatin structure. Cell. 1983 Aug;34(1):75–84. doi: 10.1016/0092-8674(83)90137-x. [DOI] [PubMed] [Google Scholar]
  40. Miyashita N. T. Molecular and phenotypic variation of the Zw locus region in Drosophila melanogaster. Genetics. 1990 Jun;125(2):407–419. doi: 10.1093/genetics/125.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Moriyama E. N., Powell J. R. Intraspecific nuclear DNA variation in Drosophila. Mol Biol Evol. 1996 Jan;13(1):261–277. doi: 10.1093/oxfordjournals.molbev.a025563. [DOI] [PubMed] [Google Scholar]
  42. O'Neil M. T., Belote J. M. Interspecific comparison of the transformer gene of Drosophila reveals an unusually high degree of evolutionary divergence. Genetics. 1992 May;131(1):113–128. doi: 10.1093/genetics/131.1.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Oakeshott J. G., Chambers G. K., Gibson J. B., Eanes W. F., Willcocks D. A. Geographic variation in G6pd and Pgd allele frequencies in Drosophila melanogaster. Heredity (Edinb) 1983 Feb;50(Pt 1):67–72. doi: 10.1038/hdy.1983.7. [DOI] [PubMed] [Google Scholar]
  44. Schaeffer S. W., Miller E. L. Estimates of gene flow in Drosophila pseudoobscura determined from nucleotide sequence analysis of the alcohol dehydrogenase region. Genetics. 1992 Oct;132(2):471–480. doi: 10.1093/genetics/132.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Schaeffer S. W., Miller E. L. Estimates of linkage disequilibrium and the recombination parameter determined from segregating nucleotide sites in the alcohol dehydrogenase region of Drosophila pseudoobscura. Genetics. 1993 Oct;135(2):541–552. doi: 10.1093/genetics/135.2.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sheen J. Y., Seed B. Electrolyte gradient gels for DNA sequencing. Biotechniques. 1988 Nov-Dec;6(10):942–944. [PubMed] [Google Scholar]
  47. Shields D. C., Sharp P. M., Higgins D. G., Wright F. "Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. Mol Biol Evol. 1988 Nov;5(6):704–716. doi: 10.1093/oxfordjournals.molbev.a040525. [DOI] [PubMed] [Google Scholar]
  48. Tachida H. A study on a nearly neutral mutation model in finite populations. Genetics. 1991 May;128(1):183–192. doi: 10.1093/genetics/128.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. Takahata N. On the overdispersed molecular clock. Genetics. 1987 May;116(1):169–179. doi: 10.1093/genetics/116.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Thackeray J. R., Kyriacou C. P. Molecular evolution in the Drosophila yakuba period locus. J Mol Evol. 1990 Nov;31(5):389–401. doi: 10.1007/BF02106054. [DOI] [PubMed] [Google Scholar]
  52. True J. R., Mercer J. M., Laurie C. C. Differences in crossover frequency and distribution among three sibling species of Drosophila. Genetics. 1996 Feb;142(2):507–523. doi: 10.1093/genetics/142.2.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Vulliamy T., Mason P., Luzzatto L. The molecular basis of glucose-6-phosphate dehydrogenase deficiency. Trends Genet. 1992 Apr;8(4):138–143. doi: 10.1016/0168-9525(92)90372-B. [DOI] [PubMed] [Google Scholar]
  54. Walthour C. S., Schaeffer S. W. Molecular population genetics of sex determination genes: the transformer gene of Drosophila melanogaster. Genetics. 1994 Apr;136(4):1367–1372. doi: 10.1093/genetics/136.4.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Watt W. B. Allozymes in evolutionary genetics: self-imposed burden or extraordinary tool? Genetics. 1994 Jan;136(1):11–16. doi: 10.1093/genetics/136.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wu C. I., Hollocher H., Begun D. J., Aquadro C. F., Xu Y., Wu M. L. Sexual isolation in Drosophila melanogaster: a possible case of incipient speciation. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2519–2523. doi: 10.1073/pnas.92.7.2519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. YOUNG W. J., PORTER J. E., CHILDS B. GLUCOSE-6-PHOSPHATE DEHYDROGENASE IN DROSOPHILA: X-LINKED ELECTROPHORETIC VARIANTS. Science. 1964 Jan 10;143(3602):140–141. doi: 10.1126/science.143.3602.140. [DOI] [PubMed] [Google Scholar]

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