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The Gene CG6767 Affects Olfactory Behavior in Drosophila melanogaster

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Abstract

Chemosensory systems mediate some of the most vital animal behaviors. However, our knowledge of the genetic mechanisms that underlie behavioral responses to olfactory cues remains fragmented. Genome-wide association mapping has greatly advanced our ability to identify candidate loci associated with variation in olfactory behavior, but functional validation of these candidates remain a necessary next step in understanding the mechanisms by which these genes influence chemoreception. In previous genome-wide association analyses, a genomic region that spans multiple polymorphic loci on the left arm of the third chromosome was found to be significantly associated with variation in olfactory behavioral responses to the odorant 2,3-butanedione, a volatile compound present in fermenting fruit. In this study, behavioral analysis of flies possessing either the major or minor haplotype for this region confirmed the association between polymorphisms in the region and variation in olfactory behavior. Moreover, functional dissection of the genes within this region using P-element insertional mutagenesis together with targeted RNAi experiments revealed that the gene CG6767, a gene of previously unknown function but predicted to encode an enzyme responsible for the synthesis and metabolism of nucleic acids, affects olfactory behavioral responses to 2,3-butanedione. Specifically, RNAi mediated knockdown of CG6767 expression in different neuroanatomical populations of the olfactory system suggests that this gene functions in local interneurons of the antennal lobe. These results reveal a new role for CG6767 and its importance in olfactory behavior.

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References

  • Acebes A, Martín-Peña A, Chevalier V, Ferrús A (2011) Synapse loss in olfactory local interneurons modifies perception. J Neurosci 31(8):2734–2745

    Article  PubMed  PubMed Central  Google Scholar 

  • Anholt RR, Dilda CL, Chang S, Fanara JJ, Kulkarni NH, Ganguly I, Rollmann SM, Kamdar KP, Mackay TF (2003) The genetic architecture of odor-guided behavior in Drosophila: epistasis and the transcriptome. Nat Genet 35:180–184

    Article  PubMed  Google Scholar 

  • Arya G, Magwire M, Huang W, Serrano-Negron Y, Mackay TF, Anholt RR (2015) The genetic basis for variation in olfactory behavior in Drosophila melanogaster. Chem Senses 40:233–243

    Article  PubMed  PubMed Central  Google Scholar 

  • Aso Y, Grübel K, Busch S, Friedrich AB, Siwanowicz I, Tanimoto H (2009) The mushroom body of adult Drosophila characterized by GAL4 drivers. J Neurogenet 23:156–172

    Article  PubMed  Google Scholar 

  • Ayyub C, Paranjape J, Rodriques V, Siddiqi O (1990) Genetics of olfactory behavior in Drosophila melanogaster. J Neurogenet 6(4):243–262

    Article  PubMed  Google Scholar 

  • Becker MA (2001) Phosphoribosylpyrophosphate synthetase and the regulation of phosphoribosylpyrophosphate production in human cells. Prog Nucleic Acid Res Mol Biol 69:115–148

    Article  PubMed  Google Scholar 

  • Becker MA, Puig JG, Mateos FA, Jimenez ML, Kim M, Simmonds HA (1988) Inherited superactivity of phosphoribosylpyrophosphate synthetase: association of uric acid overproduction and sensorineural deafness. Am J Med 85(3):383–390

    Article  PubMed  Google Scholar 

  • Brand A, Perrimon N (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Dev Camb Engl 118:401–415

    Google Scholar 

  • Brown EB, Layne JE, Zhu C, Jegga AG, Rollmann SM (2013) Genome-wide association mapping of natural variation in odour-guided behaviour in Drosophila. Genes Brain Behav 12(5):503–515

    Article  PubMed  Google Scholar 

  • Cao W, Song HJ, Gangi T, Kelkar A, Antani I, Garza D, Konolaki M (2008) Identification of novel genes that modify phenotypes induced by Alzheimer’s beta-amyloid overexpression in Drosophila. Genetics 178(3):1457–1471

    Article  PubMed  PubMed Central  Google Scholar 

  • Caron SJ, Ruta V, Abbott LF, Axel R (2013) Random convergence of olfactory inputs in the Drosophila mushroom body. Nature 497:113–117

    Article  PubMed  PubMed Central  Google Scholar 

  • Chou YH, Spletter ML, Yaksi E, Leong JC, Wilson RI, Luo L (2010) Diversity and wiring variability of olfactory local interneurons in the Drosophila antennal lobe. Nat Neurosci 13(4):439–449

    Article  PubMed  PubMed Central  Google Scholar 

  • Couto A, Alenius M, Dickson B (2005) Molecular, anatomical, and functional organization of the Drosophila olfactory system. Curr Biol 15:1535–1547

    Article  PubMed  Google Scholar 

  • Das S, Sadanandappa MK, Dervan A, Larkin A, Lee JA, Sudhakaran IP, Priya R, Heidari R, Holohan EE, Pimentel A, Gandhi A, Ito K, Sanyal S, Wang JW, Rodrigues V, Ramaswami M (2011) Plasticity of local GABAergic interneurons drives olfactory habituation. Proc Natl Acad Sci USA 108(36):E646–E654

    Article  PubMed  PubMed Central  Google Scholar 

  • de Brouwer AP, Williams KL, Duley JA, van Kuilenburg AB, Nabuurs SB, Egmont-Peterson M, Lugtenberg D, Zoetekouw L, Banning MJ, Roeffen M, Hamel BC, Weaving L, Ouvrier RA, Donald JA, Wevers RA, Christodoulou J, van Bokhoven H (2007) Arts syndrome is caused by loss-of-function mutations in PRPS1. Am J Hum Genet 81(3):507–518

    Article  PubMed  PubMed Central  Google Scholar 

  • de Brouwer AP, Duley JA, Christodoulou J (2008a) Phosphoribosylpyrophosphate synthetase superactivity. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K (eds) GeneReviews® Seattle (WA). University of Washington, Seattle

    Google Scholar 

  • de Brouwer AP, Duley JA, Christodoulou J (2008b) Arts syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K (eds) GeneReviews® Seattle (WA). University of Washington, Seattle

    Google Scholar 

  • de Brouwer AP, van Bokhoven H, Nabuurs SB, Arts WF, Christodoulou J, Duley J (2010) PRPS1 mutations: four distinct syndromes and potential treatment. Am J Hum Genet 86:506–518

    Article  PubMed  PubMed Central  Google Scholar 

  • Dietzl G, Chen D, Schnorrer F, Su KC, Barinova Y, Fellner M, Gasser B, Kinsey K, Oppel S, Scheiblauer S, Couto A, Marra V, Keleman K, Dickson BJ (2007) A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448:151–156

    Article  PubMed  Google Scholar 

  • Dobritsa AA, Van der Goes van Naters W, Warr CG, Steinbrect RA, Carlson JR (2003) Integrating the molecular and cellular basis of odor coding in the Drosophila antenna. Neuron 37:827–841

    Article  PubMed  Google Scholar 

  • Dubnau J, Tully T (1998) Gene discovery in Drosophila: new insights for learning and memory. Annu Rev Neurosci 21:407–444

    Article  PubMed  Google Scholar 

  • Duetz WA, Bouwmeester H, van Beilen JB, Witholt B (2003) Biotransformation of limonene by bacteria, fungi, yeasts, and plants. Appl Microbiol Biotechnol 61(4):269–277

    Article  PubMed  Google Scholar 

  • Duley JA, Christodoulou J, de Brouwer AP (2011) The PRPP synthetase spectrum: what does it demonstrate about nucleotide syndromes? Nucleos Nucleot Nucl 30(12):1129–1139

    Article  Google Scholar 

  • Dweck H, Ebrahim S, Khallaf M, Koenig C, Farhan A, Stieber R, Weißflog J, Svatoš A, Grosse-Wilde E, Knaden M, Hansson BS (2016) Olfactory channels associated with the Drosophila maxillary palp mediate short- and long-range attraction. Elife 5:e14925

    Article  PubMed  PubMed Central  Google Scholar 

  • Fedorowicz GM, Fry JD, Anholt RR, Mackay TF (1998) Epistatic interactions between smell-impaired loci in Drosophila melanogaster. Genetics 148:1885–1891

    PubMed  PubMed Central  Google Scholar 

  • Fisek M, Wilson RI (2014) Stereotyped connectivity and computations in higher-order olfactory neurons. Nat Neurosci 17(2):280–288

    Article  PubMed  Google Scholar 

  • Fishilevich E, Vosshall LB (2005) Genetic and functional subdivision of the Drosophila antennal lobe. Curr Biol 15:1548–1553

    Article  PubMed  Google Scholar 

  • Gao Q, Yuan B, Chess A (2000) Convergent projections of Drosophila olfactory neurons to specific glomeruli in the antennal lobe. Nat Neurosci 3:780–785

    Article  PubMed  Google Scholar 

  • García-Pavía P, Torres RJ, Rivero M, Ahmed M, García-Puig J, Becker MA (2003) Phyophoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman. Arthritis Rheum 48(7):2036–2041

    Article  PubMed  Google Scholar 

  • Goldman AL, van der Goes van Naters W, Lessing D, Warr CG, Carlson JR (2005) Coexpression of two functional odor receptors in one neuron. Neuron 45:661–666

    Article  PubMed  Google Scholar 

  • Gruntman E, Turner GC (2013) Integration of the olfactory code across dendritic claws of single mushroom body neurons. Nat Neurosci 16(12):1821–1829

    Article  PubMed  PubMed Central  Google Scholar 

  • Handford M, Rodriquez-Furián C, Orellana A (2006) Nucleotide-sugar transporters: structure, function and roles in vivo. Braz J Med Biol Res 39:1149–1158

    Article  PubMed  Google Scholar 

  • Hartman SC, Buchanan JM (1958) Biosynthesis of the purines. XXI. 5-phosphoribosylpyrophosphate amidotransferase. J Biol Chem 233(2):451–455

    PubMed  Google Scholar 

  • He X, Zhou S, St Armour GE, Anholt RR (2016) Epistatic partners of neurogenic genes modulate Drosophila olfactory behavior. Genes Brain Behav 15(2):280–290

    Article  PubMed  PubMed Central  Google Scholar 

  • Helfand S, Carlson JR (1989) Isolation and characterization of an olfactory mutant in Drosophila with a chemically specific defect. Proc Natl Acad Sci USA 86:2908–2912

    Article  PubMed  PubMed Central  Google Scholar 

  • Jefferis GS, Marin EC, Stocker RF, Luo L (2001) Target neuron prespecification in the olfactory map of Drosophila. Nature 414:204–208

    Article  PubMed  Google Scholar 

  • Kim JW, Kim HJ (2008) Charcot-Marie-Tooth Neuropathy X, Type 5. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K (eds) GeneReviews® Seattle (WA). University of Washington, Seattle

    Google Scholar 

  • Kim HJ, Sohn KM, Shy ME, Krajewski KM, Hwang M, Park JH, Jang SY, Won HH, Choi BO, Hong SH, Kim BJ, Suh YL, Ki CS, Lee SY, Kim SH, Kim JW (2007) Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, case hereditary peripheral neuropathy with hearing loss and optic neuropathy (CMTX5). Am J Hum Genet 81(3):552–558

    Article  PubMed  PubMed Central  Google Scholar 

  • Kornberg A, Lieberman I, Simms ES (1955) Enzymatic synthesis and properties of 5-phosphoribosylpyrophosphate. J Biol Chem 215(1):389–402

    PubMed  Google Scholar 

  • Larsson MC, Domingos AI, Jones WD, Chiappe ME, Amrein H, Vosshall LB (2004) Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron 43:703–714

    Article  PubMed  Google Scholar 

  • Lieberman I, Kornberg A, Simms ES (1955) Enzymatic synthesis of pyrimidine nucleotides; orotidine-5′phosphate and uridine-5-phosphate. J Biol Chem 215(1):403–451

    PubMed  Google Scholar 

  • Lilly M, Carlson JR (1990) Smellblind: A gene required for Drosophila olfaction. Genetics 124(2):293–302

    PubMed  PubMed Central  Google Scholar 

  • Liu X, Han D, Li J, Han B, Ouyang X, Cheng J, Li X, Jin Z, Wang Y, Bitner-Glindzicz M, Kong X, Xu H, Kantardzhieva A, Eavey RD, Seidman CE, Seidman JG, Du LL, Chen ZY, Dai P, Teng M, Yan D, Yuan H (2010) Loss-of-function mutations in the PRPS1 gene causes a type of nonsyndromic X-linked sensorineural deafness, DFN2. Am J Hum Genet 86(1):65–71

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu XZ, Xie D, Yuan JH, de Brouwer APM, Christodoulou J, Yan D (2013) Hearing loss and PRPS1 mutations: wide spectrum of phenotypes and potential therapy. Int J Audiol 52:23–28

    Article  PubMed  Google Scholar 

  • Loeffler M, Zameitat E (2004) Pyrimidine biosynthesis. Encyc Biol Chem 3:600–605

    Article  Google Scholar 

  • Marin EC, Jefferis GS, Komiyama T, Zhu H, Luo L (2001) Representation of the glomerular olfactory map in the Drosophila brain. Cell 109:243–255

    Article  Google Scholar 

  • Masuda-Nakagawa LM, Tanaka NK, O’Kane CJ (2005) Stereotypic and random patterns of connectivity in the larval mushroom body calyx of Drosophila. Proc Natl Acad Sci USA 102(52):19027–19032

    Article  PubMed  PubMed Central  Google Scholar 

  • Mayr D, Tilmann M, Lindinger W, Brevard H, Yeretzian C (2003) Breath-by-breath analysis of banana aroma by proton transfer mass spectrometry. Int J Mass Spectrom 223–224:743–756

    Article  Google Scholar 

  • Micheli V, Camici M, Tozzi MG, Ipata PL, Sestini S, Bertelli M, Pompucci G (2011) Neurological disorders of purine and pyrimidine metabolism. Curr Top Med Chem 11(8):923–947

    Article  PubMed  Google Scholar 

  • Mittal R, Patel K, Mittal J, Chan B, Yan D, Grati M, Liu XZ (2015) Association of PRPS1 mutations with disease phenotypes. Dis Mark. https://doi.org/10.1155/2015/127013

    Article  Google Scholar 

  • Ni JQ, Markstein M, Binari R, Pfeiffer B, Liu LP, Villalta C, Booker M, Perkins L, Perrimon N (2007) Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster. Nat Methods 5:49–51

    Article  PubMed  PubMed Central  Google Scholar 

  • Ni JQ, Liu LP, Binari R, Hardy R, Shim HS, Cavallaro A, Booker M, Pfeiffer BD, Markstein M, Wang H, Villalta C, Laverty TR, Perkins LA, Perrimon N (2009) A Drosophila resource of transgenic RNAi lines for neurogenetics. Genetics 182:1089–1100

    Article  PubMed  PubMed Central  Google Scholar 

  • Nishimura O, Yamaguchi K, Mihara S, Shibamoto T (1989) Volatile constituents of guava fruits (Psidiu guajava L.) and canned puree. J Agric Food Chem 37(1):139–142

    Article  Google Scholar 

  • Okada R, Awasaki T, Ito K (2009) Gamma-aminobutyric acid (GABA)-mediated neural connections in the Drosophila antennal lobe. J Comp Neurol 514:74–91

    Article  PubMed  Google Scholar 

  • Olsen SR, Wilson RI (2008) Lateral presynaptic inhibition mediates gain control in an olfactory circuit. Nature 452:956–960

    Article  PubMed  PubMed Central  Google Scholar 

  • Preiss J, Handler P (1958) Biosynthesis of diphosphopyridine nucleotide. I. Identification of intermediates. J Biol Chem 233(2):488–492

    PubMed  Google Scholar 

  • Ramdya P, Benton R (2010) Evolving olfactory systems on the fly. Trends Genet 26(7):307–316

    Article  PubMed  Google Scholar 

  • Richgels PK, Rollmann SM (2012) Genetic variation in odorant receptors contributes to variation in olfactory behavior in a natural population of Drosophila melanogaster. Chem Senses 37(3):229–240

    Article  PubMed  Google Scholar 

  • Root CM, Masuyama K, Green DS, Enell LE, Nassel DR, Lee CH, Wang JW (2008) A presynaptic gain control mechanism fine-tunes olfactory behavior. Neuron 59(2):311–321

    Article  PubMed  PubMed Central  Google Scholar 

  • Sadigh-Eteghad S, Sabermarouf B, Majdi A, Talebi M, Farhoudi M, Majmoudi J (2015) Amyloid-beta: a crucial factor in Alzheimer’s disease. Med Princ Pract 24(1):1–10

    Article  PubMed  Google Scholar 

  • Sambandan D, Yamamoto A, Fanara JJ, Mackay TF, Anholt RR (2006) Dynamic genetic interactions determine odor-guided behavior in Drosophila melanogaster. Genetics 174:1349–1363

    Article  PubMed  PubMed Central  Google Scholar 

  • Sampaio KL, Garruti DS, Franco MR, Janzantti NS, Da Silva MA (2011) Aroma volatiles recovered in the water phase of cashew apple (Anacardium occidentale L.) juice during concentration. J Sci Food Agric 91(10):1801–1809

    Article  PubMed  Google Scholar 

  • Shang Y, Claridge-Chang A, Sjulson L, Pypaert M, Miesenböck G (2007) Excitatory local circuits and their implications for olfactory processing in the fly antennal lobe. Cell 128:601–612

    Article  PubMed  PubMed Central  Google Scholar 

  • Stocker RF, Heimbeck G, Gendre N, de Belle JS (1997) Neuroblast ablation in Drosophila P[GAL4] lines reveals origins of olfactory interneurons. J Neurobiol 32:443–456

    Article  PubMed  Google Scholar 

  • Suh GS, Wong AM, Hergarden AC, Wang JW, Simon AF, Benzer S, Axel R, Anderson DJ (2004) A single population of olfactory sensory neurons mediates an innate avoidance behavior in Drosophila. Nature 431:854–859

    Article  PubMed  Google Scholar 

  • Swarup S, Huang W, Mackay TF, Anholt RR (2013) Analysis of natural variation reveals neurogenetic networks for Drosophila olfactory behavior. Proc Natl Acad Sci USA 110(3):1017–1022

    Article  PubMed  Google Scholar 

  • Tanaka N, Awasaki T, Shimada T, Ito K (2004) Integration of chemosensory pathways in the Drosophila second-order olfactory centers. Curr Biol 14:449–457

    Article  PubMed  Google Scholar 

  • Vosshall LB, Stocker RF (2007) Molecular architecture of smell and taste in Drosophila. Annu Rev Neurosci 30:505–533

    Article  PubMed  Google Scholar 

  • Vosshall LB, Wong A, Axel R (2000) An olfactory sensory map in the fly brain. Cell 102:147–159

    Article  PubMed  Google Scholar 

  • Wesson DW, Levy E, Nixon RA, Wilson DA (2010) Olfactory dysfunction correlates with amyloid-β burden in an Alzheimer’s disease mouse model. J Neurosci 30(2):505–514

    Article  PubMed  PubMed Central  Google Scholar 

  • Wilson RI, Laurent G (2005) Role of GABAergic inhibition in shaping odor evoked spatiotemporal patterns in the Drosophila antennal lobe. J Neurosci 25:9069–9079

    Article  PubMed  PubMed Central  Google Scholar 

  • Wong A, Wang J, Axel R (2002) Spatial representation of the glomerular map in the Drosophila protocerebrum. Cell 109:229–241

    Article  PubMed  Google Scholar 

  • Woodard C, Huang T, Sun J, Helfand SL, Carlson JR (1989) Genetic analysis of olfactory behavior in Drosophila: a new screen yields the Ota mutants. Genetics 123(2):315–326

    PubMed  PubMed Central  Google Scholar 

  • Yuan H, Liu XZ (2011) DFNX1 nonsyndromic hearing loss and deafness. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K (eds) GeneReviews® Seattle (WA). University of Washington, Seattle

    Google Scholar 

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Acknowledgements

We would like to thank John Layne for helpful discussions and critical feedback on the manuscript. We also thank members of the Rollmann lab for technical assistance and/or helpful discussions. We wish to acknowledge TRiP at the Harvard Medical School (NIH/NIGMS R01-GM084947) for providing transgenic RNAi stocks. This work was supported by the National Institutes of Health [Grant No. GM080592 to S.M.R.], the National Science Foundation Research Experiences for Undergraduates [Grant No. DBI-1262863, E.R.], and the University of Cincinnati Graduate School Dean’s Fellowship [E.B.].

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  1. Department of Biological Sciences, University of Cincinnati, Cincinnati, OH, 45221-0006, USA

    Elizabeth B. Brown & Stephanie M. Rollmann

  2. Department of Biology, Wittenberg University, Springfield, OH, 45501, USA

    Emily Rayens

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Brown, E., Rayens, E. & Rollmann, S.M. The Gene CG6767 Affects Olfactory Behavior in Drosophila melanogaster. Behav Genet 49, 317–326 (2019). https://doi.org/10.1007/s10519-019-09949-8

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