Skip to main content
SpringerLink
Log in

Wide mutational spectrum of a gene involved in hormone action and insecticide resistance in Drosophila melanogaster

  • Original Paper
  • Published:
Molecular Genetics and Genomics Aims and scope Submit manuscript

Abstract

The Methoprene-tolerant (Met) bHLH-PAS gene in Drosophila melanogaster is involved in the molecular action of juvenile hormone (JH), and mutants result in resistance to the toxic and morphogenetic effects of JH and JH agonist insecticides such as methoprene. A detailed study of Met mutants can shed light on the poorly understood action of JH as well as the molecular basis of Met resistance to JH insecticides. Nine mutant alleles bearing point mutations in Met were examined for penetrance and expressivity of three phenotypic characters: resistance, defective oogenesis, and a novel eye defect. The collection ranged from two weak alleles having less severe phenotypes to strong alleles with severe phenotypes similar to that of a null allele. The point mutations were located in both conserved and nonconserved domains. Both the eye defect, seen as severely malformed ommatidial facets in the posterior margin of the compound eye, and the oogenesis phenotype are nonconditional, whereas expression of the resistance phenotype requires treatment with JH or JH analogs (JHAs) during early metamorphosis. A proposed basis for all the phenotypic characters centers on MET action as a transcriptional regulator of ecdysone secondary-response target genes during metamorphosis. Disruption of MET function either by mutation or by JHA presence during early metamorphosis results in transcriptional misregulation of different target genes, resulting in the pathology seen in either instance. The variety of amino acid changes in MET that resulted in resistance may portend a rapid rise in resistance in response to increased use of JH insecticides in field insect populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ashburner M (1970) Effects of juvenile hormone on adult differentiation of Drosophila melanogaster. Nature 227:187–189

    Article  PubMed  CAS  Google Scholar 

  • Ashok M, Turner C, Wilson TG (1998) Insect juvenile hormone resistance gene homology with the bHLH-PAS family of transcriptional regulators. Proc Natl Acad Sci USA 95:2761–2766

    Article  PubMed  CAS  Google Scholar 

  • Baldi P, Pollastri G (2003) The principled design of large-scale recursive neural network architectures—DAG-RNNs and the protein structure prediction problem. J Mach Learn Res 4:575–603

    Article  Google Scholar 

  • Boleli IC, Bitondi MM, Figueiredo VL, Simoes ZL (2001) Mispatterning in the ommatidia of Apis mellifera pupae treated with a juvenile hormone analogue. J Morphol 249:89–99

    Article  PubMed  CAS  Google Scholar 

  • Bownes M (1989) The roles of juvenile hormone, ecdysone and the ovary in the control of Drosophila vitellogenesis. J Insect Physiol 35:409–413

    Article  CAS  Google Scholar 

  • Bownes M, Rembold H (1987) The titre of juvenile hormone during the pupal and adult stages of the life cycle of Drosophila melanogaster. Eur J Biochem 164:709–712

    Article  PubMed  CAS  Google Scholar 

  • Cornel AJ, Stanich MA, McAbee RD, Mulligan FS (2002) High level methoprene resistance in the mosquito Ochlerotatus nigromaculis (Ludlow) in central California. Pest Manag Sci 58:791–798

    Article  PubMed  CAS  Google Scholar 

  • Dame DA, Wichterman GJ, Hornby JA (1998) Mosquito (Aedes taeniorhynchus) resistance to methoprene in an isolated habitat. J Am Mosq Cont Assoc 14:200–203

    Google Scholar 

  • Dhadialla TS, Carlson GR, Le DP (l998) New insecticides with ecdysteroidal and juvenile hormone activity. Annu Rev Entomol 43:545–569

    Article  Google Scholar 

  • Dubrovsky EB, Dubrovskaya VA, Bilderback AL, Berger EM (2000) The isolation of two juvenile hormone-inducible genes in Drosophila melanogaster. Dev Biol 224:486–495

    Article  PubMed  CAS  Google Scholar 

  • Dubrovsky EB, Dubrovskaya VA, Berger EM (2002) Juvenile hormone signaling during oogenesis in Drosophila melanogaster. Insect Biochem Mol Biol 32:1555–1565

    Article  PubMed  CAS  Google Scholar 

  • Dubrovsky EB, Dubrovskaya VA, Berger EM (2004) Hormonal regulation and functional role of Drosophila E75A orphan nuclear receptor in the juvenile hormone signaling pathway. Dev Biol 268:258–270

    Article  PubMed  CAS  Google Scholar 

  • ffrench-Constant RH, Pittendrigh B, Vaughan A, Anthony N (1998) Why are there so few resistance-associated mutations in insecticide target genes? Phil Proc R Soc Lond B 353:1685–1693

    Article  CAS  Google Scholar 

  • ffrench-Constant RH, Anthony N, Aronstein K, Rocheleau T, Stilwell G (2000) Cyclodiene insecticide resistance: from molecular to population genetics. Annu Rev Entomol 49:449–466

    Article  Google Scholar 

  • Flatt T, Kawecki TJ (2004) Pleiotropic effects of methoprene-tolerant (Met), a gene involved in juvenile hormone metabolism, on life history traits in Drosophila melanogaster. Genetica 122:141–160

    Article  PubMed  CAS  Google Scholar 

  • Flatt T, Tu MP, Tatar M (2005) Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history. Bioessays 27:999–1010

    Article  PubMed  CAS  Google Scholar 

  • Frishman D, Argos P (1996) Incorporation of non-local interactions in protein secondary structure prediction from the amino acid sequence. Protein Eng 9:1333–142

    Article  Google Scholar 

  • Gilbert LI, Granger NA, Roe RM (2000) The juvenile hormones: historical facts and speculations on future research directions. Insect Biochem Mol Biol 30:617–644

    Article  PubMed  CAS  Google Scholar 

  • Godlewski J, Wang S, Wilson TG (2006) Interaction of bHLH-PAS proteins involved in juvenile hormone reception in Drosophila. Biochem Biophys Res Commun 342:1305–1311

    Article  PubMed  CAS  Google Scholar 

  • Gu Y-Z, Hogenesch JB, Bradfield CA (2000) The PAS superfamily: sensors of environmental and developmental signals. Annu Rev Pharmacol Toxicol 40:519–561

    Article  PubMed  CAS  Google Scholar 

  • Hammock BD, Mumby SM, Lee PW (1977) Mechanisms of resistance to the juvenoid methoprene in the house fly Musca domestica L. Pestic Biochem Physiol 7:261–272

    Article  CAS  Google Scholar 

  • Hankinson O (l995) The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 35:307–340

    Article  Google Scholar 

  • Horowitz AR, Kontsedalov S, Khasdan V, Ishaaya I (2005) Biotypes B and Q of Bemisia tabaci and their relevance to neonicotinoid and pyriproxyfen resistance. Arch Insect Biochem Physiol 58:216–225

    Article  PubMed  CAS  Google Scholar 

  • Jones G (1995) Molecular mechanisms of action of juvenile hormone. Annu Rev Entomol 40:147–169

    Article  PubMed  CAS  Google Scholar 

  • Jones G, Sharp PA (1997) Ultraspiracle: an invertebrate nuclear receptor for juvenile hormones. Proc Natl Acad Sci USA 94:13499–13503

    Article  PubMed  CAS  Google Scholar 

  • Kambysellis MP, Heed WB (1974) Juvenile hormone induces ovarian development in diapausing cave-dwelling Drosophila species. J Insect Physiol 20:1779–1786

    Article  PubMed  CAS  Google Scholar 

  • Kerr C, Ringo J, Dowse H, Johnson E (1997) Icebox, a recessive X-linked mutation in Drosophila causing low sexual receptivity. J Neurogenet 11:213–229

    Article  PubMed  CAS  Google Scholar 

  • Kozlova T, Thummel CS (2000) Steroid regulation of postembryonic development and reproduction in Drosophila. Trends Endocrinol Metabol 11:276–280

    Article  CAS  Google Scholar 

  • Lee WR (1976) Chemical mutagenesis. In: Novitski E (ed) The genetics and biology of Drosophila. Academic, New York, pp 1299–1341

    Google Scholar 

  • Madhavan K (1973) Morphogenetic effects of juvenile hormone and juvenile hormone mimics on adult development of Drosophila. J Insect Physiol 19:441–453

    Article  PubMed  CAS  Google Scholar 

  • McGuffin LJ, Bryson K, Jones DT (2000) The PSIPRED protein structure prediction server. Bioinformatics 16:404–4-5

    Article  PubMed  CAS  Google Scholar 

  • Minkoff C III, Wilson TG (1992) The competitive ability and fitness components of the Methoprene-tolerant (Met) Drosophila mutant resistant to juvenile hormone analog insecticides. Genetics 131:91–97

    PubMed  Google Scholar 

  • Miura K, Oda M, Makita S, Chinzei Y (2005) Characterization of the Drosophila Methoprene-tolerant gene product: juvenile hormone binding and ligand-dependent gene regulation. FEBS J 272:1169–1178

    Article  PubMed  CAS  Google Scholar 

  • Monsma SA, Booker R (1996) Genesis of the adult retina and outer optic lobes of the moth, Manduca sexta. II. Effects of deafferentation and developmental hormone manipulation. J Comp Neurol 367:21–35

    Article  PubMed  CAS  Google Scholar 

  • Moore AW, Barbel S, Jan LY, Jan YN (2000) A genomewide survey of basic helix–loop–helix factors in Drosophila. Proc Natl Acad Sci USA 97:10436–10441

    Article  PubMed  CAS  Google Scholar 

  • Mutero A, Pralavorio M, Bride J-M, Fournier D (1994) Resistance-associated point mutations in insecticide-insensitive acetylcholinesterase. Proc Natl Acad Sci USA 91:5922–5926

    Article  PubMed  CAS  Google Scholar 

  • Postlethwait JH (1974) Juvenile hormone and the adult development of Drosophila. Biol Bull 147:119–135

    Article  PubMed  CAS  Google Scholar 

  • Postlethwait JH, Jones J (1978) Endocrine control of larval fat body histolysis in normal and mutant Drosophila melanogaster. J Exp Zool 203:207–214

    Article  PubMed  CAS  Google Scholar 

  • Postlethwait JH, Weiser K (1973) Vitellogenesis induced by juvenile hormone in the female sterile mutant apterous-four in Drosophila melanogaster. Nat New Biol 244:284–285

    Article  PubMed  CAS  Google Scholar 

  • Qiao CL, Raymond M (1995) The same esterase B1 haplotype is amplified in insecticide-resistant mosquitoes of the Culex pipens complex from the Americas and China. Heredity 74:339–345

    Article  PubMed  CAS  Google Scholar 

  • Restifo LL, Wilson TG (1998) A juvenile hormone agonist reveals distinct developmental pathways mediated by ecdysone-inducible Broad Complex transcription factors. Dev Genet 22:141–159

    Article  PubMed  CAS  Google Scholar 

  • Riddiford LM (1993) Hormones and Drosophila development. In: Bate M, Martinez Arias A (eds) The development of Drosophila melanogaster. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 899–939

    Google Scholar 

  • Riddiford LM (1994) Cellular and molecular actions of juvenile hormone. I. General considerations and premetamorphic actions. Adv Insect Physiol 24:213–274

    CAS  Google Scholar 

  • Riddiford LM (1996) Molecular aspects of juvenile hormone action in insect metamorphosis. In: Gilbert LI, Tata JR, Atkinson BG (eds) Metamorphosis: postembryonic reprogramming of gene expression in amphibian and insect cells. Academic, San Diego, pp 223–251

    Google Scholar 

  • Riddiford LM, Ashburner M (1991) Effects of juvenile hormone mimics on larval development and metamorphosis of Drosophila melanogaster. Gen Comp Endocrinol 82:172–183

    Article  PubMed  CAS  Google Scholar 

  • Rost B (1996) PHD: predicting one-dimensional protein structure by profile based neural networks. Meth Enzymol 266:525–539

    Article  PubMed  CAS  Google Scholar 

  • Sakuma M (1998) PROBIT analysis of preference data. Appl Entomol Zool 33:339–347

    Google Scholar 

  • Shemshedini L, Wilson TG (1990) Resistance to juvenile hormone and an insect growth regulator in Drosophila is associated with an altered cytosolic juvenile hormone binding protein. Proc Natl Acad Sci USA 87:2072–2076

    Article  PubMed  CAS  Google Scholar 

  • Shemshedini L, Lanoue M, Wilson TG (1990) Evidence for a juvenile hormone receptor involved in protein synthesis in Drosophila melanogaster. J Biol Chem 265:1913–1918

    PubMed  CAS  Google Scholar 

  • Sliter TJ, Sedlak BJ, Baker FC, Schooley PA (1987) Juvenile hormone in Drosophila melanogaster: identification and titer determination during development. Insect Biochem 17:161–165

    Article  CAS  Google Scholar 

  • Soderlund DM, Knipple DC (2003) The molecular biology of knockdown resistance to pyrethroid insecticides. Insect Biochem Mol Biol 33:563–577

    Article  PubMed  CAS  Google Scholar 

  • Soller M, Bownes M, Kubli E (1999) Control of oocyte maturation in sexually mature Drosophila females. Dev Biol 208:337–351

    Article  PubMed  CAS  Google Scholar 

  • Staal GB (1975) Insect growth regulators with juvenile hormone activity. Annu Rev Entomol 20:417–460

    Article  PubMed  CAS  Google Scholar 

  • Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292:107–110

    Article  PubMed  CAS  Google Scholar 

  • Thummel CS (1996) Flies on steroids: Drosophila metamorphosis and the mechanisms of steroid hormone action. Trends Genet 12:306–310

    Article  PubMed  CAS  Google Scholar 

  • Vais H, Williamson MS, Devonshire AL, Usherwood PNR (2001) The molecular interactions of pyrethroid insecticides with insect and mammalian sodium channels. Pest Manag Sci 57:877–888

    Article  PubMed  CAS  Google Scholar 

  • Wheeler DE, Nijhout HF (2003) A perspective for understanding the modes of juvenile hormone action as a lipid signaling system. Bioessays 25:994–1001

    Article  PubMed  CAS  Google Scholar 

  • Williamson MS, Martinez-Torres D, Hick CA, Devonshire AL (l996) Identification of mutations in the housefly para-type sodium channel gene associated with knockdown resistance (kdr) to pyrethroid insecticides. Mol Gen Genet 251:51–60

    Article  Google Scholar 

  • Wilson TG (1982) A correlation between juvenile hormone deficiency and vitellogenic oocyte degeneration in Drosophila melanogaster. Wilhelm Roux Arch Entwicklungsmech Org 191:257–263

    Article  CAS  Google Scholar 

  • Wilson TG (1996) Genetic evidence that mutants of the Methoprene-tolerant gene of Drosophila melanogaster are null mutants. Arch Insect Biochem Physiol 32:641–649

    Article  PubMed  CAS  Google Scholar 

  • Wilson TG (2004) The molecular site of action of juvenile hormone and juvenile hormone insecticides during metamorphosis: how these compounds kill insects. J Insect Physiol 50:111–121

    Article  PubMed  CAS  Google Scholar 

  • Wilson TG, Ashok M (1998) Insecticide resistance resulting from an absence of target-site gene product. Proc Natl Acad Sci USA 95:14040–14044

    Article  PubMed  CAS  Google Scholar 

  • Wilson TG, Fabian J (1986) A Drosophila melanogaster mutant resistant to a chemical analog of juvenile hormone. Dev Biol 118:190–201

    Article  PubMed  CAS  Google Scholar 

  • Wilson TG, Fabian J (1987) Selection of methoprene-resistant mutants of Drosophila melanogaster. In: Law J (ed) Molecular entomology. UCLA symposia on molecular and cellular biology, New Series, pp 179–188

  • Wilson TG, Yerushalmi Y, Donnell DM, Restifo LL (2006) Interaction between hormonal signaling pathways in Drosophila melanogaster as revealed by genetic interaction between Methoprene-tolerant and Broad-Complex. Genetics 172:253–264

    Article  PubMed  CAS  Google Scholar 

  • Wyatt GR, Davey KG (1996) Cellular and molecular actions of juvenile hormone. II. Roles of juvenile hormone in adult insects. Adv Insect Physiol 26:1–155

    CAS  Google Scholar 

  • Yamamoto K, Chadarevian A, Pellegrini M (1988) Juvenile hormone action mediated in male accessory glands of Drosophila by calcium and kinase C. Science 239:916–919

    Article  PubMed  CAS  Google Scholar 

  • Zhou X, Riddiford LM (2002) Broad specifies pupal development and mediates the ‘status quo’ action of juvenile hormone on the pupal–adult transformation in Drosophila and Manduca. Development 129:2259–2269

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Judy Fabian and Jamie Fitch, who were involved in isolating several of the alleles in mutant screens. This work was funded by grants from the National Institutes of Health (AI052290) and the National Science Foundation (IBN 0322136) to T.G.W., and VEGA 2/3025/23 and APVT-51-027402 to R.F.

Author information

Authors and Affiliations

  1. Department of Entomology, Ohio State University, Columbus, OH, 43210, USA

    Thomas G. Wilson & Shaoli Wang

  2. Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlárska 3, 83306, Bratislava – Kramáre, Slovakia

    Milan Beňo & Robert Farkaš

Authors
  1. Thomas G. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shaoli Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Milan Beňo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert Farkaš
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas G. Wilson.

Additional information

Communicated by G. Reuter

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilson, T.G., Wang, S., Beňo, M. et al. Wide mutational spectrum of a gene involved in hormone action and insecticide resistance in Drosophila melanogaster . Mol Genet Genomics 276, 294–303 (2006). https://doi.org/10.1007/s00438-006-0138-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00438-006-0138-4

Keywords

Search

Navigation