Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2001 Jan;157(1):283–294. doi: 10.1093/genetics/157.1.283

Quantitative trait loci for the monoamine-related traits heart rate and headless behavior in Drosophila melanogaster.

K Ashton 1, A P Wagoner 1, R Carrillo 1, G Gibson 1
PMCID: PMC1461470  PMID: 11139509

Abstract

Drosophila melanogaster appears to be well suited as a model organism for quantitative pharmacogenetic analysis. A genome-wide deficiency screen for haploinsufficient effects on prepupal heart rate identified nine regions of the genome that significantly reduce (five deficiencies) or increase (four deficiencies) heart rate across a range of genetic backgrounds. Candidate genes include several neurotransmitter receptor loci, particularly monoamine receptors, consistent with results of prior pharmacological manipulations of heart rate, as well as genes associated with paralytic phenotypes. Significant genetic variation is also shown to exist for a suite of four autonomic behaviors that are exhibited spontaneously upon decapitation, namely, grooming, grasping, righting, and quivering. Overall activity levels are increased by application of particular concentrations of the drugs octopamine and nicotine, but due to high environmental variance both within and among replicate vials, the significance of genetic variation among wild-type lines for response to the drugs is difficult to establish. An interval mapping design was also used to map two or three QTL for each behavioral trait in a set of recombinant inbred lines derived from the laboratory stocks Oregon-R and 2b.

Full Text

The Full Text of this article is available as a PDF (255.5 KB).

Selected References

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

  1. Andretic R., Chaney S., Hirsh J. Requirement of circadian genes for cocaine sensitization in Drosophila. Science. 1999 Aug 13;285(5430):1066–1068. doi: 10.1126/science.285.5430.1066. [DOI] [PubMed] [Google Scholar]
  2. Anholt R. R., Lyman R. F., Mackay T. F. Effects of single P-element insertions on olfactory behavior in Drosophila melanogaster. Genetics. 1996 May;143(1):293–301. doi: 10.1093/genetics/143.1.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bull S. B., Toma C., Mirea L. Disease-marker associations: power and heterogeneity in independent population samples. Genet Epidemiol. 1999;17 (Suppl 1):S509–S514. doi: 10.1002/gepi.1370170782. [DOI] [PubMed] [Google Scholar]
  4. Catalano M. The challenges of psychopharmacogenetics. Am J Hum Genet. 1999 Sep;65(3):606–610. doi: 10.1086/302559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dubnau J., Tully T. Gene discovery in Drosophila: new insights for learning and memory. Annu Rev Neurosci. 1998;21:407–444. doi: 10.1146/annurev.neuro.21.1.407. [DOI] [PubMed] [Google Scholar]
  6. Ferrandon D., Jung A. C., Criqui M., Lemaitre B., Uttenweiler-Joseph S., Michaut L., Reichhart J., Hoffmann J. A. A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway. EMBO J. 1998 Aug 10;17(5):1217–1227. doi: 10.1093/emboj/17.5.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Friddle C., Koskela R., Ranade K., Hebert J., Cargill M., Clark C. D., McInnis M., Simpson S., McMahon F., Stine O. C. Full-genome scan for linkage in 50 families segregating the bipolar affective disease phenotype. Am J Hum Genet. 2000 Jan;66(1):205–215. doi: 10.1086/302697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gu G. G., Singh S. Pharmacological analysis of heartbeat in Drosophila. J Neurobiol. 1995 Nov;28(3):269–280. doi: 10.1002/neu.480280302. [DOI] [PubMed] [Google Scholar]
  9. Hen R. Structural and functional conservation of serotonin receptors throughout evolution. EXS. 1993;63:266–278. doi: 10.1007/978-3-0348-7265-2_14. [DOI] [PubMed] [Google Scholar]
  10. Hirsh J. Decapitated Drosophila: a novel system for the study of biogenic amines. Adv Pharmacol. 1998;42:945–948. doi: 10.1016/s1054-3589(08)60903-5. [DOI] [PubMed] [Google Scholar]
  11. Homyk T., Sheppard D. E. Behavioral Mutants of DROSOPHILA MELANOGASTER. I. Isolation and Mapping of Mutations Which Decrease Flight Ability. Genetics. 1977 Sep;87(1):95–104. doi: 10.1093/genetics/87.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jones B. C., Tarantino L. M., Rodriguez L. A., Reed C. L., McClearn G. E., Plomin R., Erwin V. G. Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry. Pharmacogenetics. 1999 Oct;9(5):607–617. [PubMed] [Google Scholar]
  13. Keightley P. D., Morris K. H., Ishikawa A., Falconer V. M., Oliver F. Test of candidate gene--quantitative trait locus association applied to fatness in mice. Heredity (Edinb) 1998 Dec;81(Pt 6):630–637. doi: 10.1046/j.1365-2540.1998.00450.x. [DOI] [PubMed] [Google Scholar]
  14. Long A. D., Mullaney S. L., Mackay T. F., Langley C. H. Genetic interactions between naturally occurring alleles at quantitative trait loci and mutant alleles at candidate loci affecting bristle number in Drosophila melanogaster. Genetics. 1996 Dec;144(4):1497–1510. doi: 10.1093/genetics/144.4.1497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lyman R. F., Mackay T. F. Candidate quantitative trait loci and naturally occurring phenotypic variation for bristle number in Drosophila melanogaster: the Delta-Hairless gene region. Genetics. 1998 Jun;149(2):983–998. doi: 10.1093/genetics/149.2.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mackay T. F. The nature of quantitative genetic variation revisited: lessons from Drosophila bristles. Bioessays. 1996 Feb;18(2):113–121. doi: 10.1002/bies.950180207. [DOI] [PubMed] [Google Scholar]
  17. Newby L. M., Jackson F. R. Drosophila ebony mutants have altered circadian activity rhythms but normal eclosion rhythms. J Neurogenet. 1991 Feb;7(2-3):85–101. doi: 10.3109/01677069109066213. [DOI] [PubMed] [Google Scholar]
  18. Nuzhdin S. V., Pasyukova E. G., Dilda C. L., Zeng Z. B., Mackay T. F. Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9734–9739. doi: 10.1073/pnas.94.18.9734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Osborne K. A., Robichon A., Burgess E., Butland S., Shaw R. A., Coulthard A., Pereira H. S., Greenspan R. J., Sokolowski M. B. Natural behavior polymorphism due to a cGMP-dependent protein kinase of Drosophila. Science. 1997 Aug 8;277(5327):834–836. doi: 10.1126/science.277.5327.834. [DOI] [PubMed] [Google Scholar]
  20. Pasyukova E. G., Vieira C., Mackay T. F. Deficiency mapping of quantitative trait loci affecting longevity in Drosophila melanogaster. Genetics. 2000 Nov;156(3):1129–1146. doi: 10.1093/genetics/156.3.1129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Phillis R. W., Bramlage A. T., Wotus C., Whittaker A., Gramates L. S., Seppala D., Farahanchi F., Caruccio P., Murphey R. K. Isolation of mutations affecting neural circuitry required for grooming behavior in Drosophila melanogaster. Genetics. 1993 Mar;133(3):581–592. doi: 10.1093/genetics/133.3.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ramos A., Moisan M. P., Chaouloff F., Mormède C., Mormède P. Identification of female-specific QTLs affecting an emotionality-related behavior in rats. Mol Psychiatry. 1999 Sep;4(5):453–462. doi: 10.1038/sj.mp.4000546. [DOI] [PubMed] [Google Scholar]
  23. Rosbash M. Molecular control of circadian rhythms. Curr Opin Genet Dev. 1995 Oct;5(5):662–668. doi: 10.1016/0959-437x(95)80037-9. [DOI] [PubMed] [Google Scholar]
  24. Sugumaran M., Giglio L., Kundzicz H., Saul S., Semensi V. Studies on the enzymes involved in puparial cuticle sclerotization in Drosophila melanogaster. Arch Insect Biochem Physiol. 1992;19(4):271–283. doi: 10.1002/arch.940190406. [DOI] [PubMed] [Google Scholar]
  25. True J. R., Edwards K. A., Yamamoto D., Carroll S. B. Drosophila wing melanin patterns form by vein-dependent elaboration of enzymatic prepatterns. Curr Biol. 1999 Dec 2;9(23):1382–1391. doi: 10.1016/s0960-9822(00)80083-4. [DOI] [PubMed] [Google Scholar]
  26. Vadasz C., Saito M., Balla A., Kiraly I., Vadasz C., 2nd, Gyetvai B., Mikics E., Pierson D., Brown D., Nelson J. C. Mapping of quantitative trait loci for ethanol preference in quasi-congenic strains. Alcohol. 2000 Feb;20(2):161–171. doi: 10.1016/s0741-8329(99)00068-3. [DOI] [PubMed] [Google Scholar]
  27. Vieira C., Pasyukova E. G., Zeng Z. B., Hackett J. B., Lyman R. F., Mackay T. F. Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster. Genetics. 2000 Jan;154(1):213–227. doi: 10.1093/genetics/154.1.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Walter M. F., Zeineh L. L., Black B. C., McIvor W. E., Wright T. R., Biessmann H. Catecholamine metabolism and in vitro induction of premature cuticle melanization in wild type and pigmentation mutants of Drosophila melanogaster. Arch Insect Biochem Physiol. 1996;31(2):219–233. doi: 10.1002/(SICI)1520-6327(1996)31:2<219::AID-ARCH9>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  29. Williams N. M., Rees M. I., Holmans P., Norton N., Cardno A. G., Jones L. A., Murphy K. C., Sanders R. D., McCarthy G., Gray M. Y. A two-stage genome scan for schizophrenia susceptibility genes in 196 affected sibling pairs. Hum Mol Genet. 1999 Sep;8(9):1729–1739. doi: 10.1093/hmg/8.9.1729. [DOI] [PubMed] [Google Scholar]
  30. Yellman C., Tao H., He B., Hirsh J. Conserved and sexually dimorphic behavioral responses to biogenic amines in decapitated Drosophila. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4131–4136. doi: 10.1073/pnas.94.8.4131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zhao L. P., Prentice R., Shen F., Hsu L. On the assessment of statistical significance in disease-gene discovery. Am J Hum Genet. 1999 Jun;64(6):1739–1753. doi: 10.1086/512072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zornik E., Paisley K., Nichols R. Neural transmitters and a peptide modulate Drosophila heart rate. Peptides. 1999;20(1):45–51. doi: 10.1016/s0196-9781(98)00151-x. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES