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. 1994 Apr;136(4):1329–1340. doi: 10.1093/genetics/136.4.1329

Evidence for Positive Selection in the Superoxide Dismutase (Sod) Region of Drosophila Melanogaster

R R Hudson 1, K Bailey 1, D Skarecky 1, J Kwiatowski 1, F J Ayala 1
PMCID: PMC1205914  PMID: 8013910

Abstract

DNA sequence variation in a 1410-bp region including the Cu,Zn Sod locus was examined in 41 homozygous lines of Drosophila melanogaster. Fourteen lines were from Barcelona, Spain, 25 were from California populations and the other two were from laboratory stocks. Two common electromorphs, SOD(S) and SOD(F), are segregating in the populations. Our sample of 41 lines included 19 Sod(S) and 22 Sod(F) alleles (henceforward referred to as Slow and Fast alleles). All 19 Slow alleles were identical in sequence. Of the 22 Fast alleles sequenced, nine were identical in sequence and are referred to as the Fast A haplotypes. The Slow allele sequence differed from the Fast A haplotype at a single nucleotide site, the site that accounts for the amino acid difference between SOD(S) and SOD(F). There were nine other haplotypes among the remaining 13 Fast alleles sequenced. The overall level of nucleotide diversity (π) in this sample is not greatly different than that found at other loci in D. melanogaster. It is concluded that the Slow/Fast polymorphism is a recently arisen polymorphism, not an old balanced polymorphism. The large group of nearly identical haplotypes suggests that a recent mutation, at the Sod locus or tightly linked to it, has increased rapidly in frequency to around 50%, both in California and Spain. The application of a new statistical test demonstrates that the occurrence of such large numbers of haplotypes with so little variation among them is very unlikely under the usual equilibrium neutral model. We suggest that the high frequency of some haplotypes is due to natural selection at the Sod locus or at a tightly linked locus.

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Selected References

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  1. Ayala F. J., Powell J. R., Tracey M. L., Mourão C. A., Pérez-Salas S. Enzyme variability in the Drosophila willistoni group. IV. Genic variation in natural populations of Drosophila willistoni. Genetics. 1972 Jan;70(1):113–139. doi: 10.1093/genetics/70.1.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Ceballos-Picot I., Nicole A., Sinet P. M. Cellular clones and transgenic mice overexpressing copper-zinc superoxide dismutase: models for the study of free radical metabolism and aging. EXS. 1992;62:89–98. doi: 10.1007/978-3-0348-7460-1_10. [DOI] [PubMed] [Google Scholar]
  4. Ceballos I., Javoy-Agid F., Delacourte A., Defossez A., Nicole A., Sinet P. M. Parkinson's disease and Alzheimer's disease: neurodegenerative disorders due to brain antioxidant system deficiency? Adv Exp Med Biol. 1990;264:493–498. doi: 10.1007/978-1-4684-5730-8_75. [DOI] [PubMed] [Google Scholar]
  5. Chovnick A., Gelbart W., McCarron M. Organization of the Rosy locus in Drosophila melanogaster. Cell. 1977 May;11(1):1–10. doi: 10.1016/0092-8674(77)90312-9. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Graf J. D., Ayala F. J. Genetic variation for superoxide dismutase level in Drosophila melanogaster. Biochem Genet. 1986 Apr;24(3-4):153–168. doi: 10.1007/BF00502785. [DOI] [PubMed] [Google Scholar]
  9. Hale L. R., Singh R. S. A comprehensive study of genic variation in natural populations of Drosophila melanogaster. IV. Mitochondrial DNA variation and the role of history vs. selection in the genetic structure of geographic populations. Genetics. 1991 Sep;129(1):103–117. doi: 10.1093/genetics/129.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Hudson R. R., Kaplan N. L. Statistical properties of the number of recombination events in the history of a sample of DNA sequences. Genetics. 1985 Sep;111(1):147–164. doi: 10.1093/genetics/111.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Hudson R. R. Properties of a neutral allele model with intragenic recombination. Theor Popul Biol. 1983 Apr;23(2):183–201. doi: 10.1016/0040-5809(83)90013-8. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Kwiatowski J., González F., Ayala F. J. Drosophila simulans Cu-Zn superoxide dismutase gene sequence. Nucleic Acids Res. 1989 Aug 25;17(16):6735–6735. doi: 10.1093/nar/17.16.6735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kwiatowski J., Patel M., Ayala F. J. Drosophila melanogaster Cu, Zn superoxide dismutase gene sequence. Nucleic Acids Res. 1989 Feb 11;17(3):1264–1264. doi: 10.1093/nar/17.3.1264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kwiatowski J., Skarecky D., Ayala F. J. Structure and sequence of the Cu,Zn Sod gene in the Mediterranean fruit fly, Ceratitis capitata: intron insertion/deletion and evolution of the gene. Mol Phylogenet Evol. 1992 Mar;1(1):72–82. doi: 10.1016/1055-7903(92)90037-h. [DOI] [PubMed] [Google Scholar]
  21. Lee Y. M., Ayala F. J. Superoxide dismutase in Drosophila melanogaster. Mutation site difference between two electromorphs. FEBS Lett. 1985 Jan 1;179(1):115–119. doi: 10.1016/0014-5793(85)80203-9. [DOI] [PubMed] [Google Scholar]
  22. Lee Y. M., Friedman D. J., Ayala F. J. Complete amino acid sequence of copper-zinc superoxide dismutase from Drosophila melanogaster. Arch Biochem Biophys. 1985 Sep;241(2):577–589. doi: 10.1016/0003-9861(85)90583-1. [DOI] [PubMed] [Google Scholar]
  23. Lee Y. M., Misra H. P., Ayala F. J. Superoxide dismutase in Drosophila melanogaster: biochemical and structural characterization of allozyme variants. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7052–7055. doi: 10.1073/pnas.78.11.7052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Peng T. X., Moya A., Ayala F. J. Two modes of balancing selection in Drosophila melanogaster: overcompensation and overdominance. Genetics. 1991 Jun;128(2):381–391. doi: 10.1093/genetics/128.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Roff D. A., Bentzen P. The statistical analysis of mitochondrial DNA polymorphisms: chi 2 and the problem of small samples. Mol Biol Evol. 1989 Sep;6(5):539–545. doi: 10.1093/oxfordjournals.molbev.a040568. [DOI] [PubMed] [Google Scholar]
  27. Rosen D. R., Siddique T., Patterson D., Figlewicz D. A., Sapp P., Hentati A., Donaldson D., Goto J., O'Regan J. P., Deng H. X. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993 Mar 4;362(6415):59–62. doi: 10.1038/362059a0. [DOI] [PubMed] [Google Scholar]
  28. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Sawyer S. Statistical tests for detecting gene conversion. Mol Biol Evol. 1989 Sep;6(5):526–538. doi: 10.1093/oxfordjournals.molbev.a040567. [DOI] [PubMed] [Google Scholar]
  31. Seager R. D., Ayala F. J. Chromosome interactions in Drosophila melanogaster. I. Viability studies. Genetics. 1982 Nov;102(3):467–483. doi: 10.1093/genetics/102.3.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Seto N. O., Hayashi S., Tener G. M. Cloning, sequence analysis and chromosomal localization of the Cu-Zn superoxide dismutase gene of Drosophila melanogaster. Gene. 1989 Jan 30;75(1):85–92. doi: 10.1016/0378-1119(89)90385-5. [DOI] [PubMed] [Google Scholar]
  33. Singh R. S., Hickey D. A., David J. Genetic Differentiation between Geographically Distant Populations of DROSOPHILA MELANOGASTER. Genetics. 1982 Jun;101(2):235–256. doi: 10.1093/genetics/101.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stephens J. C. Statistical methods of DNA sequence analysis: detection of intragenic recombination or gene conversion. Mol Biol Evol. 1985 Nov;2(6):539–556. doi: 10.1093/oxfordjournals.molbev.a040371. [DOI] [PubMed] [Google Scholar]
  35. Strobeck C. Average number of nucleotide differences in a sample from a single subpopulation: a test for population subdivision. Genetics. 1987 Sep;117(1):149–153. doi: 10.1093/genetics/117.1.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Taniguchi N. Clinical significances of superoxide dismutases: changes in aging, diabetes, ischemia, and cancer. Adv Clin Chem. 1992;29:1–59. doi: 10.1016/s0065-2423(08)60221-8. [DOI] [PubMed] [Google Scholar]

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