Advertisement

Biological Effects of Single-Nucleotide Polymorphisms in the Drosophila melanogaster Malic Enzyme Locus

  • Simran Baath
  • Thomas J. S. MerrittEmail author
Original Article

Abstract

A pair of amino acid polymorphisms within the Drosophila melanogaster Malic enzyme (Men) locus presents an interesting case of genetic variation that appears to be under selection. The two alleles at each site are biochemically distinct, but their biological effects are unknown. One polymorphic site is near the active site and the other is buried within the protein. Strikingly, in twelve different populations, the first polymorphism is always found at approximately a 50:50 allelic frequency, whereas the second polymorphism is always found at approximately 90:10. The consistency of the frequencies between populations suggests that the polymorphisms are under selection and it is possible that balancing selection is at play. We used 16 lines of flies to create the nine genotypes needed to quantify both effects of the polymorphic sites and possible genetic background effects, which we found to be widespread. The alleles at each site differ, but in different biochemical characteristics. The first site significantly influences MEN Km and Vmax, whereas the second site affects the Km and the Vmax/Km ratio (relative activity). Interestingly, the rarest allele is the most biochemically distinct. We also assayed three more distal phenotypes, triglyceride concentration, carbohydrate concentration, and longevity. In all cases, the phenotypes of the heterozygous genotypes are intermediate between those of the respective homozygotes suggesting that if balancing selection is maintaining the observed allele frequencies it is not through non-linear combinations of the biochemical phenotypes.

Keywords

Genetic variation Single-nucleotide polymorphism Balancing selection Genetic background Malic enzyme Drosophila melanogaster 

Notes

Acknowledgements

This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (RGPIN-2018–05551) and Canada Research Chair (950–230113) to TJSM. The authors thank Drs Nadia Singh, Guangdong Yang, and Eric Gauthier for reading earlier versions of this manuscript.

References

  1. Bernard KE, Parkes TL, Merritt TJS (2011) A model of oxidative stress management: moderation of carbohydrate metabolizing enzymes in SOD1-null Drosophila melanogaster. PLoS ONE 6(9):e24518CrossRefGoogle Scholar
  2. Bing X, Rzezniczak TZ, Bateman JR, Merritt TJS (2014) Transvection-Based gene regulation in drosophila is a complex and plastic trait. G3 4(11):2175–87Google Scholar
  3. Biswal HS, Gloaguen E, Loquais Y, Tardivel B, Mons M (2012) Strength of NH⋯S hydrogen bonds in methionine residues revealed by gas-phase IR/UV spectroscopy. J Phys Chem Lett 3(6):755–759CrossRefGoogle Scholar
  4. Chakrabartty A, Schellman JA, Baldwin RL (1991) Large differences in the helix propensities of alanine and glycine. Nature 351:586–588CrossRefGoogle Scholar
  5. Charlesworth D, Charlesworth B (1987) Inbreeding depression and its evolutionary consequences. Annu Rev Ecol Syst 18:237–268CrossRefGoogle Scholar
  6. Chow CY (2016) Bringing genetic background into focus. Nat Rev Genet 17(2):63–64CrossRefGoogle Scholar
  7. Dudash MR, Fenster CB (2000) Inbreeding and outbreeding depression in fragmented populations. In: Genetics, demography and viability of fragmented populations. Cambridge University Press, CambridgeGoogle Scholar
  8. Dixon SJ, Costanzo M, Baryshnikova A, Andrews B, Boone C (2009) Systematic mapping of genetic interaction networks. Annu Rev Genet 43:601–625CrossRefGoogle Scholar
  9. Geer BW, Lindel DL, Lindel DM (1979) Relationship of the oxidative pentose shunt pathway to lipid synthesis in Drosophila melanogaster. Biochem Genet 17(9–10):881–895CrossRefGoogle Scholar
  10. Hall John G (1985) Temperature-related kinetic differentiation of glucosephosphate isomerase alleloenzymes isolated from the blue mussel Mytilus edulis. Biochem Genet 23(9–10):705–728CrossRefGoogle Scholar
  11. Hall JG, Koehn RK (1983) The evolution of enzyme catalytic efficiency and adaptive inference from steady-state kinetic data. In: Hecht MK, Wallace B, Prance GT (eds) Evolutionary biology, 16th ed. Springer Nature, New YorkGoogle Scholar
  12. Hartl DL, Clark AG (2006) Principles of Population Genetics, 4th edn. Sinaur Press, SunderlandGoogle Scholar
  13. Huang Wen et al (2014) Natural variation in genome architecture among 205 Drosophila melanogaster genetic reference panel lines. Genome Res 24(7):1193–1208CrossRefGoogle Scholar
  14. Kalmus H (1945) Adaptative and selective responses of a population of Drosophila melanogaster containing e and E+ to differences in temperature, humidity and to selection for developmental speed. J Genet 47(1):58–63CrossRefGoogle Scholar
  15. Lessel CE, Parkes TL, Dickinson J, Merritt TJS (2017) Sex and genetic background influence Superoxide dismutase (CSOD)-related phenotypic variation in Drosophila melanogaster. G3 7:2651-2664Google Scholar
  16. Lewontin RC, Hubby JL (1966) A molecular approach to the study of genic heterozygosity in natural populations. II. Amount of variation and degree of heterozygosity in Drosophila pseudoobscura. Genetics 54:595–609Google Scholar
  17. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 25(4):402–408CrossRefGoogle Scholar
  18. Lum TE, Merritt TJS (2011) Nonclassical regulation of transcription: interchromosomal iInteractions at the Malic enzyme Locus of Drosophila melanogaster. Genetics 189(3):837–849CrossRefGoogle Scholar
  19. Mackay TFC (2004) The genetic architecture of quantitative traits: lessons from Drosophila. Curr Opin Genet Dev 4(3):253–257CrossRefGoogle Scholar
  20. Mellert David J, Truman James W (2012) Transvection is common throughout the Drosophila genome. Genetics 191(4):1129–1141CrossRefGoogle Scholar
  21. Merritt TJS, Duvernell D, Eanes WF (2005) Natural and synthetic alleles provide complementary insights into the nature of selection acting on the Men polymorphism of Drosophila melanogaster”. Genetics 171(4):1707–1718CrossRefGoogle Scholar
  22. Merritt Thomas J S, Sezgin Efe, Zhu Chen Tseh, Eanes Walter F (2006) Triglyceride pools, flight and activity variation at the Gpdh locus in Drosophila melanogaster. Genetics 172(1):293–304CrossRefGoogle Scholar
  23. Merritt Thomas J S et al (2009) Quantifying Interactions within the NADP(H) enzyme network in Drosophila Melanogaster. Genetics 182(2):565–574CrossRefGoogle Scholar
  24. Morris JR, Chen JL, Geyer PK, Wu CT (1998) Two modes of transvection: enhancer action in trans and bypass of a chromatin insulator in cis. Proc Natl Acad Sci USA 95(18):10740–10745CrossRefGoogle Scholar
  25. Noble GP, Dolph PJ, Supattapone S (2016) Interallelic transcriptional enhancement as an in vivo measure of transvection in Drosophila melanogaster. G3 6:3139–3148Google Scholar
  26. Pal Debnath, Chakrabarti Pinak (2001) Non-hydrogen bond interactions involving the methionine sulfur atom. J Biomol Struct Dyn 9(1):115–128CrossRefGoogle Scholar
  27. Ralser M, Heeren G, Breitenbach M, Lehrach H, Krobitsch S (2006) Triose phosphate isomerase deficiency is caused by altered dimerization–not catalytic inactivity–of the mutant enzymes. PLoS One 1(1):e30Google Scholar
  28. Rzezniczak TZ, Merritt TJS (2012) Interactions of NADP-reducing enzymes across varying environmental conditions: a model of biological complexity. G3 2(12):1613–23Google Scholar
  29. Rzezniczak TZ, Lum TE, Harniman R, Merritt TJS (2012) A combination of structural and cis-regulatory factors drives biochemical differences in Drosophila melanogaster Malic enzyme. Biochem Genet 50(11–12):823–837CrossRefGoogle Scholar
  30. Sezgin E, Duvernell DD, Matzkin LM, Duan Y, Zhu C-T, Verrelli BC, Eanes WF (2004) Single-locus latitudinal clines and their relationship to temperate adaptation in metabolic genes and derived alleles in Drosophila melanogaster. Genetics 168(2):923–931CrossRefGoogle Scholar
  31. Watt WB, Dean AM (2000) Molecular-functional studies of adaptive genetic variation in prokaryotes and eukaryotes. Annu Rev Genet 34:593–622CrossRefGoogle Scholar
  32. Wilton AN, Laurie-Ahlberg CC, Emigh TH, Curtsinger JW (1982) naturally occurring enzyme activity variation in Drosophila melanogaster. II. Relationships among enzymes. Genetics 102(2):207–221Google Scholar
  33. Wise EM, Ball EG (1964) Malic enzyme and lipogenesis. Proc Natl Acad Sci USA 52(1933):1255–1263CrossRefGoogle Scholar
  34. Wolf JB (2003) Genetic architecture and evolutionary constraint when the environment contains genes. Proc Natl Acad Sci USA 100(8):4655–4660CrossRefGoogle Scholar
  35. Wu C-T, Morris JR (1999) Transvection and Other homology effects. Curr Opin Genet Dev 9(2):237–246CrossRefGoogle Scholar
  36. Ying W (2008) NAD+ /NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxid Redox Signal 10(2):179–206CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemistry & BiochemistryLaurentian UniversitySudburyCanada

Personalised recommendations