Skip to main content
SpringerLink
Log in

The Function and Evolution of the Halloween Genes: The Pathway to the Arthropod Molting Hormone

  • Chapter
Ecdysone: Structures and Functions

The Halloween genes of Drosophila melanogaster were first described in the 1980s using cytogenetic methodology. During the past several years the genes have been cloned, expressed and the gene products have been characterized as cytochrome P450 enzymes (CYPs) and four have been functionalized as mediating the final steps in the biosynthesis of the arthropod molting hormone, 20-hydroxyecdysone (20E). A fifth has now been studied in detail and shown to be required for ecdysteroidogenesis but its exact function has yet to be elucidated. Since both insects and crustaceans utilize 20E as their principal molting hormone we have examined by BLAST search the genome of Daphnia and demonstrated the existence of Halloween gene orthologs in this crustacean, indicating that these genes play an identical role in this class as they do in insects. Further examination of the data bases representing Lepidoptera, Coleoptera, Hymenoptera and other Diptera allowed the development of a phylogenetic scheme for this gene family and suggests that the Halloween genes and vertebrate steroidogenic P450s originated from common ancestors that were perhaps destined for steroidogenesis, and arose before the deuterostome-arthropod split.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Beckstead RB, Thummel CS (2006) Indicted: worms caught using steroids. Cell 124:1137–1140

    Article  PubMed  CAS  Google Scholar 

  • Blais C, Dauphin-Villemant C, Kovganko N, Girault JP, Descoins C Jr, Lafont R (1996) Evidence for the involvement of 3-oxo-delta 4 intermediates in ecdysteroid biosynthesis. Biochem J 320(Pt 2):413–419

    PubMed  CAS  Google Scholar 

  • Chavez VM, Marques G, Delbecque JP, Kobayashi K, Hollingsworth M, Burr J, Natzle JE, O'Connor MB (2000) The Drosophila disembodied gene controls late embryonic morphogenesis and codes for a cytochrome P450 that regulates embryonic ecdysone levels. Development 127:4115–4126

    PubMed  CAS  Google Scholar 

  • Chen S, Li X (2007) Transposable elements are enriched within or in close proximity to xenobiotic-metabolizing cytochrome CYP genes. BMC Evol Biol 7:46

    Article  PubMed  Google Scholar 

  • Claudianos C, Ranson H, Johnson RM, Biswas S, Schuler MA, Berenbaum MR, Feyereisen R, Oakeshott JG (2006) A deficit of detoxification enzymes: pesticide sensitivity and environmental response in the honeybee. Insect Mol Biol 15:615–636

    Article  PubMed  CAS  Google Scholar 

  • Corbin CJ, Mapes SM, Marcos J, Shackleton CH, Morrow D, Safe S, Wise T, Joe Ford J, Conley AJ (2004) Paralogues of porcine aromatase cytochrome CYP: a novel hydroxylase activity is associated with the survival of a duplicated gene. Endocrinology 145:2157–2164

    Article  PubMed  CAS  Google Scholar 

  • Dai J-D, Gilbert LI (1991) Metamorphosis of the corpus allatum and degeneration of the prothoracic glands during the larval-pupal-adult transformation of Drosophila melanogaster: a cytophysi-ological analysis of the ring gland. Dev Biol 144:309–326

    Article  PubMed  CAS  Google Scholar 

  • Emerson JJ, Kaessmann H, Betran E, Long M (2004) Extensive gene traffic on the mammalian X chromosome. Science 303:537–540

    Article  PubMed  CAS  Google Scholar 

  • Feyereisen R (2005) Insect cytochrome P450. In: Gilbert LI, Iatrou K, Gill S (Eds), Comprehensive Molecular Insect Science, Vol. 4. Elsevier, Oxford, pp. 1–77

    Google Scholar 

  • Feyereisen R, Durst F (1978) Ecdysterone biosynthesis: a microsomal cytochrome P-450-linked ecdys-one 20-monooxygenase from tissues of the African migratory locust. Eur J Biochem 88: 37–47

    Article  PubMed  CAS  Google Scholar 

  • Force A, Lynch M, Pickett FB, Amores A, Yan Y, Postlethwait J (1999) Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151:1531–1545

    PubMed  CAS  Google Scholar 

  • Gayral P, Caminade P, Boursot P, Galtier N (2007) The evolutionary fate of recently duplicated retrogenes in mice. J Evol Biol 20:617–626

    Article  PubMed  CAS  Google Scholar 

  • Gilbert LI (2004) Halloween genes encode P450 enzymes that mediate steroid hormone biosynthesis in Drosophila melanogaster. Mol Cell Endocrinol 215:1–10

    Article  PubMed  CAS  Google Scholar 

  • Gilbert LI, Warren JT (2005) A molecular genetic approach to the biosynthesis of the insect steroid molting hormone. Vitam Horm 73:31–57

    Article  PubMed  CAS  Google Scholar 

  • Gilbert LI, Rybczynski R, Warren JT (2002) Control and biochemical nature of the ecdysteroidogenic pathway. Annu Rev Entomol 47:883–916

    Article  PubMed  CAS  Google Scholar 

  • Glenner H, Thomsen PF, Hebsgaard MB, Sørensen MV, Willerslev E (2006) The origin of insects. Science 314:1883–1884

    Article  PubMed  CAS  Google Scholar 

  • Gotoh O (1992) Substrate recognition sites in cytochrome CYP family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequence. J Biol Chem 267:83–90

    PubMed  CAS  Google Scholar 

  • Henrich V, Tucker R, Maroni G, Gilbert LI (1987a) The ecdysoneless (ecd1-ts) mutation disrupts ecdys-teroid synthesis autonomously in the ring gland of Drosophila melanogaster. Dev Bio 120:50–55

    Article  CAS  Google Scholar 

  • Henrich V, Pak M, Gilbert LI (1987b) Neural factors that stimulate ecdysteroid synthesis by the larval ring gland of Drosophila melanogaster. J Comp Physiol 157:643–549

    Google Scholar 

  • Henrich V, Sliter TJ, Lubahn DB, MacIntyre A, Gilbert LI (1990) A steroid/thyroid hormone receptor superfamily member in Drosophila melanogaster that shares sequence similarity with a mammalian homologue. Nucleic Acids Res 18:4143–4148

    Article  PubMed  CAS  Google Scholar 

  • Keller A (2007) A cultural and natural history of the fly. (book review). PLOS Biol 5:0978–0979

    Article  CAS  Google Scholar 

  • Köhler HR, Kloas W, Shirling M, Lutz I, Reye AL, Langen JS, Triebskorn R, Nagel R, Schönfelder G (2007) Sex steroid receptor evolution and signaling in aquatic invertebrates. Ecotoxicology 16:131–143

    Article  PubMed  Google Scholar 

  • Lachaise F, Le Roux A, Hubert M, Lafont R (1993) The molting gland of crustaceans: localization, activity, and endocrine control. J Crustacean Biol 13:198–234

    Article  Google Scholar 

  • Lafont R, Mathieu M (2007) Steroids in aquatic invertebrates. Ecotoxicology 16:109–130

    Article  PubMed  CAS  Google Scholar 

  • Lafont R, Dauphin-Villemant C, Warren JT, Rees H (2005) Ecdysteroid chemistry and biochemistry. In: Gilbert LI, Iatrou K, Gill S (Eds), Comprehensive Molecular Insect Science, Vol. 3. Elsevier, Oxford, pp. 125–195

    Google Scholar 

  • Lepesheva GI, Waterman MR (2007) Sterol 14α-demethylase cytochrome CYP (CYP51), a CYP in all biological kingdoms. Biochim Biophys Acta 1770:467–477

    PubMed  CAS  Google Scholar 

  • Lezzi M, Gilbert LI (1969) Control of gene activities in the polytene chromosomes of Chironomus tentans by ecdysone and juvenile hormone. Proc Natl Acad Sci USA 64:498–503

    Article  PubMed  CAS  Google Scholar 

  • Lezzi M, Gilbert LI (1970) Differential effects of K+ and Na+ on specific bands of isolated polytene chromosomes of Chironomus tentans. J Cell Sci 6:615–627

    PubMed  CAS  Google Scholar 

  • Li W, Yang J, Gu X (2005) Expression divergence between duplicate genes. Trends Genet 21: 602–607

    Article  PubMed  Google Scholar 

  • Mitchell MHJ, Crooks JR, Keogh DP, Smith SL (1999) Ecdysone 20-monooxygenase activity during larval-pupal-adult development of the tobacco hornworm, Manduca sexta. Arch Insect Biochem Physiol 41:24–32

    Article  CAS  Google Scholar 

  • Motola DL, Cummins CL, Rottiers V, Sharma KK, Li T, Li Y, Suino-Powell K, Xu HE, Auchus RJ, Antebi A, Mangelsdorf1 DJ (2006) Identification of ligands for DAF-12 that govern Dauer formation and reproduction in C. elegans. Cell 124:1209–1223

    Article  PubMed  CAS  Google Scholar 

  • Namiki T, Niwa R, Sakudoh T, Shirai K, Takeuchi H, Kataoka H (2005) Cytochrome P450/Spook: a regulator for ecdysone synthesis in insects. Biochem Biophys Res Commun 337:367–374

    Article  PubMed  CAS  Google Scholar 

  • Nelson DR, Strobel HW (1987) Evolution of cytochrome P—450 proteins. Mol Biol Evol 4: 572–593

    PubMed  CAS  Google Scholar 

  • Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Guengerich FP, Estabrook RW, Gunsalus IC, Gonzales FJ, Nebert DW (1996) P450 superfamily: update on new sequences, gene mapping, accession numbers, and nomenclature. Pharmacogenetics 6:1–42

    Article  PubMed  CAS  Google Scholar 

  • Neubueser D, Warren JT, Gilbert LI, Cohen SM (2005) molting defective is required for ecdysone biosynthesis. Dev Biol 280:362–372

    Article  PubMed  CAS  Google Scholar 

  • Niwa R, Matsuda T, Yoshiyama T, Namiki T, Mita K, Fujimoto Y, Kataoka H (2004) CYP306A1, a cytochrome P450 enzyme is essential for ecdysteroid biosynthesis in the prothoracic glands of Bombyx and Drosoophila. J Biol Chem 279:35942–35949

    Article  PubMed  CAS  Google Scholar 

  • Niwa R, Sakudoh T, Namiki T, Saida K, Fujimoto Y, Kataoka H (2005) The ecdysteroidogenic P 450 CYP302A1/disembodied from the silkworm, Bombyx mori, is transcriptionally regulated by prothoracicotropic hormone. Insect Mol Biol 14:563–571

    Article  PubMed  CAS  Google Scholar 

  • Ono H, Rewitz KF, Shinoda T, Itoyama K, Petryk A, Rybczynski R, Jarcho M, Warren, JT, Marques G, Shimell MJ, Gilbert LI, O'Connor MB (2006) Spook and spookier code for stage-specific components of the biosynthetic pathway in Diptera. Dev Biol 298:555–5780

    Article  PubMed  CAS  Google Scholar 

  • Parvy JP, Blais C, Bernard F, Warren JT, Petryk A, Gilbert LI, O'Connor MB, Dauphin-Villemant C (2005) A role for βFTZ-F1 in regulating ecdysteroid titers during post-embryonic development in Drosophila melanogaster. Dev Biol 282:84–94

    Article  PubMed  CAS  Google Scholar 

  • Payne AH, Hales DB (2004) Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocrinol Rev 25:947–970

    Article  CAS  Google Scholar 

  • Petryk A, Warren JT, Marques G, Jarcho MP, Gilbert LI, Parvy J-P, Dauphin-Villemant C, O'Connor MB (2003) Shade is the Drosophila P450 enzyme that mediates the hydroxylation of cdysone to the steroid insect molting hormone 20-hydroxyecdysone. Proc Natl Acad Sci USA 100:13773–13778

    Article  PubMed  CAS  Google Scholar 

  • Rewitz KF, Rybczynski R, Warren JT, Gilbert LI (2006a) Identification, characterization and developmental expression of Halloween genes encoding P450 enzymes mediating ecdysone biosynthesis in the tobacco hornworm, Manduca sexta. Insect Biochem Mol Biol 36:188–199

    Article  CAS  Google Scholar 

  • Rewitz KF, Rybczynski R, Warren JT, Gilbert LI (2006b) Developmental expression of Manduca shade, the P450 mediating the final step in molting hormone synthesis. Mol Cell Endocrinol 247:166–174

    Article  CAS  Google Scholar 

  • Rewitz KF, O'Connor MB, Gilbert LI (2007) Molecular evolution of the insect Halloween family of cytochrome P450s: phylogeny, gene organization and functional conservation. Insect Biochem Mol Biol 37:741–753

    Article  PubMed  CAS  Google Scholar 

  • Richard D, Applebaum SW, Sliter TJ, Baker FC, Schooley DA, Reuter CC, Henrich V, Gilbert LI (1989) Juvenile hormone bisepoxide biosynthesis in vitro by the ring gland of Drosophila melanogaster: a putative juvenile hormone in the higher Diptera. Proc Natl Acad Sci USA 86:1421–1425

    Article  PubMed  CAS  Google Scholar 

  • Roberts B, Gilbert LI (1986) Ring gland and prothoracic gland sensitivity to interspecific protho-racicotropic hormone extracts. J Comp Physiol 156:767–771

    CAS  Google Scholar 

  • Roberts B, Whitten J, Gilbert LI (1976) Patterns of incorporation of tritiated thymidine by the dorsal polytene foot-pad nuclei of Sarcophaga bullata (Sarcophagidae: Diptera). Chromosoma 54:127–140

    Article  PubMed  CAS  Google Scholar 

  • Rogozin IB, Wolf YI, Sorokin AV, Mirkin BG, Koonin EV (2003) Remarkable interkingdom conservation of intron position and massive, lineage-specific intron loss and gain in eukaryotic evolution. Curr Biol 13:1512–1517

    Article  PubMed  CAS  Google Scholar 

  • Rybczynski R, Gilbert LI (1994) Changes in general and specific protein synthesis that accompany ecdysteroid synthesis in stimulated prothoracic glands of Manduca sexta. Insect Biochem Mol Biol 24:175–189

    Article  PubMed  CAS  Google Scholar 

  • Saunders D, Henrich V, Gilbert LI (1989) Induction of diapause in Drosophila melanogaster: photoperiodic regulation and impact of arrhythmic mutations on time measurement. Proc Natl Acad Sci USA 86:3748–3752

    Article  PubMed  CAS  Google Scholar 

  • Savard J, Tautz D, Richards S, Weinstock GM, Gibbs RA, Werren JH, Tettelin H, Lercher MJ (2006) Phylogenomic analysis reveals bees and wasps (Hymenoptera) at the base of the radiation of holometabolous insects. Genome Res 16:1334–1338

    Article  PubMed  CAS  Google Scholar 

  • Sieglaff DH, Duncan KA, Brown MR (2005) Expression of genes encoding proteins involved in ecdysteroidogenesis in the female mosquito, Aedes aegypti. Insect Biochem Mol Biol 35: 471–490

    Article  PubMed  CAS  Google Scholar 

  • Sliter TJ, Gilbert LI (1992) Developmental arrest and ecdysone deficiency resulting from mutations at the dre4 locus of Drosophila. Genetics 130:555–568

    PubMed  CAS  Google Scholar 

  • Sliter TJ, Henrich V, Tucker RL, Gilbert LI (1989) The genetics of the Dras3-Roughened-ecdysoneless chromosomal region (62B3–4 to 62D3–4) in Drosophila melanogaster: analysis of recessive lethal mutations. Genetics 123:327–336

    PubMed  CAS  Google Scholar 

  • Smith CD, Shu S, Mungall CJ, Karpen GH (2007) The release 5.1 annotation of Drosophila mela-nogaster heterochromatin. Science 316:1586–1591

    Article  PubMed  CAS  Google Scholar 

  • Smith SL, Bollenbacher WE, Cooper DY, Schleyer H, Wielgus JJ, Gilbert LI (1979) Ecdysone 20-monooxygenase: characterization of an insect cytochrome p-450 dependent steroid hydrox-ylase. Mol Cell Endocrinol 15:111–133

    Article  PubMed  CAS  Google Scholar 

  • Smith SL, Bollenbacher WE, Gilbert LI (1983) Ecdysone 20-monooxygenase activity during larval-pupal development of Manduca sexta. Mol Cell Endocrinol 31:227–251

    Article  PubMed  CAS  Google Scholar 

  • Srivastava US, Gilbert LI (1968) Juvenile hormone: effects on a higher dipteran. Science 161:61–62

    Article  PubMed  CAS  Google Scholar 

  • Srivastava US, Gilbert LI (1969) The influence of juvenile hormone on the metamorphosis of Sarcophaga bullata. J Insect Physiol 15:177–189

    Article  CAS  Google Scholar 

  • Sroka P, Gilbert LI (1971) Studies on the endocrine control of post-emergence ovarian maturation in Manduca sexta. J Insect Physiol 17:2409–2419

    Article  PubMed  CAS  Google Scholar 

  • Sztal T, Chung H, Gramzow L, Daborn PJ, Batterham P, Robin C (2007) Two independent duplications forming the Cyp307a genes in Drosophila. Insect Biochem Mol Biol 37: 1044–1053

    Article  PubMed  CAS  Google Scholar 

  • Taylor JS, Raes J (2004) Duplication and divergence: the evolution of new genes and old ideas. Annu Rev Genet 38:615–643

    Article  PubMed  CAS  Google Scholar 

  • Warren JT, Gilbert LI (1986) Ecdysone metabolism and distribution during the pupal-adult development of Manduca sexta. Insect Biochem 16:65–82

    Article  CAS  Google Scholar 

  • Warren JT, Wismar J, Subrahmanyam B, Gilbert LI (2001) Woc (without children) gene control of ecdysone biosynthesis in Drosophila melanogaster. Mol Cell Endocrinol 181:1–14

    Article  PubMed  CAS  Google Scholar 

  • Warren JT, Petryk A, Marques G, Jarcho M, Parvy J-P, Dauphin-Villemaont C, O'Connor MB, Gilbert LI (2002) Molecular and biochemical characterization of two P450 enzymes in the ecdysteroidogenic pathway of Drosophila melanogaster. Proc Natl Acad Sci USA 99: 11043–11048

    Article  PubMed  CAS  Google Scholar 

  • Warren JT, Petryk A, Marques G, Jarcho M, Parvy JP, Shinoda T, Itoyama K, Kobayashi J, Jarcho M, Li Y, O'Connor MB, Dauphin-Villemant C, Gilbert LI (2004) Phantom encodes the 25-hydroxylase of Drosophila melanogaster and Bombyx mori: a P450 enzyme critical in ecdysone biosynthesis. Insect Biochem Mol Biol 34:991–1010

    Article  PubMed  CAS  Google Scholar 

  • Warren JT, Yerushalmi Y, Shimell MJ, O'Connor MB, Gilbert LI (2006) Discrete pulses of molting hormone, 20-hydroxyecdysone, during late larval development of Drosophila mela-nogaster: correlations with changes in gene activity. Dev Dynam 235:315–326

    Article  CAS  Google Scholar 

  • Wismar J, Habtemichael N, Warren JT, Dai JD, Gilbert LI, Gateff E (2000) The mutation without children (rgl) causes ecdysteroid deficiency in third-instar larvae of Drosophila melanogaster. Dev Biol 226:1–17

    Article  PubMed  CAS  Google Scholar 

  • Yoshiyama T, Namiki T, Mita K, Kataoka H, Niwa R (2006) Neverland is an evolutionarily conserved Rieske-domain protein that is essential for ecdysone synthesis and insect growth. Development 133:565–2574

    Article  Google Scholar 

  • Zhang J (2003) Evolution by gene duplication: an update. Trends Ecol Evol 18:292–298

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, University of North Carolina, Chapel Hill, NC, 27599-3280, USA

    Lawrence I. Gilbert

  2. Department of Science, Systems and Models, Roskilde University, PO Box 260, Roskilde, DK-4000, Denmark

    Kim F. Rewitz

Authors
  1. Lawrence I. Gilbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kim F. Rewitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kim F. Rewitz .

Editor information

Editors and Affiliations

  1. Laboratory of Agrozoology Faculty of Bioscience Engineering, Ghent University, Belgium

    Guy Smagghe

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science + Business Media B.V

About this chapter

Cite this chapter

Gilbert, L.I., Rewitz, K.F. (2009). The Function and Evolution of the Halloween Genes: The Pathway to the Arthropod Molting Hormone. In: Smagghe, G. (eds) Ecdysone: Structures and Functions. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9112-4_9

Download citation

Publish with us

Policies and ethics

Search

Navigation