Halloween genes

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20-hydroxyecdysone, a key regulatory hormone involved in cuticle development in insects 20-Hydroxyecdysone.svg
20-hydroxyecdysone, a key regulatory hormone involved in cuticle development in insects

The halloween genes are a set of genes identified in Drosophila melanogaster that influence embryonic development. All of the genes code for cytochrome P450 enzymes in the ecdysteroidogenic pathway (biosynthesis of ecdysone from cholesterol). Ecdysteroids such as 20-hydroxyecdysone and ecdysone influence many of the morphological, physiological, biochemical changes that occur during molting in insects. [1]

Steroid hormones control many aspects of reproduction, development, and homeostasis in higher organisms. [2] [3] In arthropods, steroid hormones play equal or even more vital developmental roles, especially in controlling the patterns of gene expression between developmental stages. [1] The forerunner of steroid hormones is cholesterol that vertebrates can synthesize. In contrast, insects need to take up cholesterol in their diet. In 20E biosynthesis, a series of hydroxylation takes place and the genes that encoded the enzymes for catalyzing the hydroxylation were first identified in Drosphilia. [4] Insects have been around since about 500 million years before the first mammal and have continued to be evolutionarily successful. This suggests that exogenous cholesterol was required for the mechanism for steroid hormone biosynthesis. [5]

First elaborated by research groups led by Wieschaus and Nüsslein-Volhard in the early 1980s, the name was coined to collectively name a series of Drosophila embryonic lethal mutations associated with defective exoskeleton formation. Early research showed that when one of the Halloween genes was mutated, fly embryos would die before the exoskeleton was created. [6] Mutants in the halloween gene series include the spook, spookier, phantom (or phm), disembodied (or dib), shadow (or sad), and shade genes.

The mutant homozygous embryos appear phenotypically normal until mid-embryonic development where the embryos exhibit abnormal developmental characters. Some abnormal characteristics include undifferentiated cuticle, a failure of head involution, dorsal closure, compact appearance and abnormal looping of the hindgut. These embryos die before reaching the end of embryogenesis. [5]

The mechanisms of transcriptional regulation of the Halloween genes appear to differ from one another. [7]

Descriptions

The spook gene (Cyp307a1) is expressed in the prothoracic gland, [8] and in conjunction with the gene product of spookier (Cyp307a2), converts 7-dehydrocholesterol to Δ4-diketol. [6]

The phantom gene (Cyp306a1) encodes an encoding the microsomal 25-hydroxylase. Strong expression of phm is restricted to the prothoracic gland cells of the Drosophila larval ring gland. [9] The gene product converts 2,22,25dE-ketodiol to 2,22dE-ketotriol. [6]

The disembodied gene (Cyp302a1) codes for a cytochrome P450 enzyme that adds a hydroxyl group to the carbon-22 position of 2,22,dE-ketotriol to make 2-deoxyecdysone. [10] dib mutants are defective in producing their cuticle and have severe defects in morphological processes such as head involution, dorsal closure and gut development. [11]

The shadow gene (Cyp315a1) product produces ecdysone from 2-deoxyecdysone. [6]

The shade gene (Cyp314a1) codes for an Ecdysone 20-monooxygenase responsible for adding a hydroxyl group to the 20C-position of ecdysone to make 20-hydroxyecdysone, the final step in the biosynthetic pathway. [12]

Related Research Articles

<span class="mw-page-title-main">Ecdysone</span> Precursor of an insect hormone

Ecdysone is a prohormone of the major insect molting hormone 20-hydroxyecdysone, secreted from the prothoracic glands. It is of steroidal structure. Insect molting hormones are generally called ecdysteroids. Ecdysteroids act as moulting hormones of arthropods but also occur in other related phyla where they can play different roles. In Drosophila melanogaster, an increase in ecdysone concentration induces the expression of genes coding for proteins that the larva requires. It causes chromosome puffs to form in polytene chromosomes. Recent findings in the laboratory of Chris Q. Doe have found a novel role of this hormone in regulating temporal gene transitions within neural stem cells of the fruit fly.

<span class="mw-page-title-main">20-Hydroxyecdysone</span> Chemical compound

20-Hydroxyecdysone is a naturally occurring ecdysteroid hormone which controls the ecdysis (moulting) and metamorphosis of arthropods. It is therefore one of the most common moulting hormones in insects, crabs, etc. It is also a phytoecdysteroid produced by various plants, including Cyanotis vaga, Ajuga turkestanica and Rhaponticum carthamoides where its purpose is presumably to disrupt the development and reproduction of insect pests. In arthropods, 20-hydroxyecdysone acts through the ecdysone receptor. Although mammals lack this receptor, 20-hydroxyecdysone affects mammalian biological systems. 20-Hydroxyecdysone is an ingredient of some supplements that aim to enhance physical performance. In humans, it is hypothesized to bind to the estrogen receptor beta (ERβ) protein-coding gene.

<span class="mw-page-title-main">Aldosterone synthase</span> Protein-coding gene in the species Homo sapiens

Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme catalyzes sequential hydroxylations of the steroid angular methyl group at C18 after initial 11β-hydroxylation. It is encoded by the CYP11B2 gene in humans.

<span class="mw-page-title-main">CYP17A1</span> Mammalian protein found in Homo sapiens

Cytochrome P450 17A1 is an enzyme of the hydroxylase type that in humans is encoded by the CYP17A1 gene on chromosome 10. It is ubiquitously expressed in many tissues and cell types, including the zona reticularis and zona fasciculata of the adrenal cortex as well as gonadal tissues. It has both 17α-hydroxylase and 17,20-lyase activities, and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. More specifically, the enzyme acts upon pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 position (C17) of the steroid D ring, or acts upon 17α-hydroxyprogesterone and 17α-hydroxypregnenolone to split the side-chain off the steroid nucleus.

<span class="mw-page-title-main">Cholesterol side-chain cleavage enzyme</span> Mammalian protein found in Homo sapiens

Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an acronym for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reaction in the process of steroidogenesis in all mammalian tissues that specialize in the production of various steroid hormones.

<span class="mw-page-title-main">Cholesterol 7 alpha-hydroxylase</span> Protein-coding gene in the species Homo sapiens

Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.

<span class="mw-page-title-main">21-Hydroxylase</span> Human enzyme that hydroxylates steroids

Steroid 21-hydroxylase is a protein that in humans is encoded by the CYP21A2 gene. The protein is an enzyme that hydroxylates steroids at the C21 position on the molecule. Naming conventions for enzymes are based on the substrate acted upon and the chemical process performed. Biochemically, this enzyme is involved in the biosynthesis of the adrenal gland hormones aldosterone and cortisol, which are important in blood pressure regulation, sodium homeostasis and blood sugar control. The enzyme converts progesterone and 17α-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol, respectively, within metabolic pathways which in humans ultimately lead to aldosterone and cortisol creation—deficiency in the enzyme may cause congenital adrenal hyperplasia.

<span class="mw-page-title-main">Steroid 11β-hydroxylase</span> Protein found in mammals

Steroid 11β-hydroxylase, also known as steroid 11β-monooxygenase, is a steroid hydroxylase found in the zona glomerulosa and zona fasciculata of the adrenal cortex. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene. The enzyme is involved in the biosynthesis of adrenal corticosteroids by catalyzing the addition of hydroxyl groups during oxidation reactions.

<span class="mw-page-title-main">Cytochrome P450 reductase</span> Mammalian protein found in Homo sapiens

Cytochrome P450 reductase is a membrane-bound enzyme required for electron transfer from NADPH to cytochrome P450 and other heme proteins including heme oxygenase in the endoplasmic reticulum of the eukaryotic cell.

<span class="mw-page-title-main">Cholesterol 24-hydroxylase</span> Protein family

Cholesterol 24-hydroxylase, also commonly known as cholesterol 24S-hydroxylase, cholesterol 24-monooxygenase, CYP46, or CYP46A1, is an enzyme that catalyzes the conversion of cholesterol to 24S-hydroxycholesterol. It is responsible for the majority of cholesterol turnover in the human central nervous system. The systematic name of this enzyme class is cholesterol,NADPH:oxygen oxidoreductase (24-hydroxylating).

Ecdysone 20-monooxygenase (EC 1.14.99.22) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">CYP26A1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 26A1 is a protein that in humans is encoded by the CYP26A1 gene.

<span class="mw-page-title-main">CYP4F2</span> Enzyme protein in the species Homo sapiens

Cytochrome P450 4F2 is a protein that in humans is encoded by the CYP4F2 gene. This protein is an enzyme, a type of protein that catalyzes chemical reactions inside cells. This specific enzyme is part of the superfamily of cytochrome P450 (CYP) enzymes, and the encoding gene is part of a cluster of cytochrome P450 genes located on chromosome 19.

<span class="mw-page-title-main">CYP7B1</span> Protein-coding gene in the species Homo sapiens

25-hydroxycholesterol 7-alpha-hydroxylase also known as oxysterol and steroid 7-alpha-hydroxylase is an enzyme that in humans is encoded by the CYP7B1 gene. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.

<span class="mw-page-title-main">Ecdysone receptor</span>

The ecdysone receptor is a nuclear receptor found in arthropods, where it controls development and contributes to other processes such as reproduction. The receptor is a non-covalent heterodimer of two proteins, the EcR protein and ultraspiracle protein (USP). It binds to and is activated by ecdysteroids. Insect ecdysone receptors are currently better characterized than those from other arthropods, and mimics of ecdysteroids are used commercially as caterpillar-selective insecticides.

<span class="mw-page-title-main">CYP4Z1</span> Protein-coding gene in the species Homo sapiens

CYP4Z1 is a protein that in humans is encoded by the CYP4Z1 gene.

<span class="mw-page-title-main">CYP2U1</span> Protein-coding gene in the species Homo sapiens

CYP2U1 is a protein that in humans is encoded by the CYP2U1 gene

Cytochrome P450, family 305, also known as CYP305, is an animal cytochrome P450 family found in insect genome. The first gene identified in this family is the CYP305A1 from the Drosophila melanogaster.

Juvenile hormone acid O-methyltransferase (JHAMT) is a ~33 kDa enzyme that catalyzes the conversion of inactive precursors of Juvenile hormones (JHs) to active JHs in the final stages of JH biosynthesis in the corpora allata of insects. More specifically, the enzyme catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to the carboxylate group of JH precursors.

In biochemistry, cytochrome P450 enzymes have been identified in all kingdoms of life: animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses. As of 2018, more than 300,000 distinct CYP proteins are known.

References

  1. 1 2 Gilbert LI, Rybczynski R, Warren JT (2002). "Control and biochemical nature of the ecdysteroidogenic pathway". Annual Review of Entomology. 47: 883–916. doi:10.1146/annurev.ento.47.091201.145302. PMID   11729094.
  2. ↑ Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM (1995). "The nuclear receptor superfamily: the second decade". Cell. 83 (6): 835–39. doi:10.1016/0092-8674(95)90199-X. PMC   6159888 . PMID   8521507.
  3. ↑ Okamoto, Naoki; Fujinaga, Daiki; Yamanaka, Naoki (2023), "Steroid hormone signaling: What we can learn from insect models", Vitamins and Hormones, vol. 123, Elsevier, pp. 525–554, doi:10.1016/bs.vh.2022.12.006, ISBN   978-0-443-13455-5, PMID   37717997 , retrieved 2024-07-29
  4. ↑ Rewitz, K.F.; Rybczynski, R.; Warren, J.T.; Gilbert, L.I. (2006-12-01). "The Halloween genes code for cytochrome P450 enzymes mediating synthesis of the insect moulting hormone". Biochemical Society Transactions. 34 (6): 1256–1260. doi:10.1042/BST0341256. ISSN   0300-5127. PMID   17073797.
  5. 1 2 Gilbert, Lawrence I (February 2004). "Halloween genes encode P450 enzymes that mediate steroid hormone biosynthesis in Drosophila melanogaster". Molecular and Cellular Endocrinology. 215 (1–2): 1–10. doi:10.1016/j.mce.2003.11.003. PMID   15026169. S2CID   9215493.
  6. 1 2 3 4 Gilbert LI. (2008). "Drosophila is an inclusive model for human diseases, growth and development". Molecular and Cellular Endocrinology. 293 (1–2): 25–31. doi:10.1016/j.mce.2008.02.009. PMID   18374475. S2CID   27545060.
  7. ↑ Kamiyama, Takumi; Niwa, Ryusuke (2022-02-08). "Transcriptional Regulators of Ecdysteroid Biosynthetic Enzymes and Their Roles in Insect Development". Frontiers in Physiology. 13. doi: 10.3389/fphys.2022.823418 . ISSN   1664-042X. PMC   8863297 . PMID   35211033.
  8. ↑ Namiki T, Niwa R, Sakudoh T, Shirai K, Takeuchi H, Kataoka H (2005). "Cytochrome 450 CYP307A1/Spook: A regulator for ecdysone synthesis in insects". Biochemical and Biophysical Research Communications. 337 (1): 367–74. doi:10.1016/j.bbrc.2005.09.043. PMID   16188237.
  9. ↑ Warren JT, Petryk A, Marqués G, 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 Biochemistry and Molecular Biology. 34 (9): 991–1010. Bibcode:2004IBMB...34..991W. doi:10.1016/j.ibmb.2004.06.009. PMID   15350618.
  10. ↑ Gilbert LI. (2004). "Halloween genes encode P450 enzymes that mediate steroid hormone biosynthesis in Drosophila melanogaster". Molecular and Cellular Endocrinology. 215 (1–2): 1–10. doi:10.1016/j.mce.2003.11.003. PMID   15026169. S2CID   9215493.
  11. ↑ Chávez VM, Marqués 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 enzyme that regulates embryonic ecdysone levels". Development. 127 (19): 4115–26. doi:10.1242/dev.127.19.4115. PMID   10976044.
  12. ↑ Petryk A, Warren JT, Marques G, Jarcho MP, Gilbert LI, Kahler J, Parvy JP, Li YT, Dauphin-Villemant C, O'Connor MB (2003). "Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone". Proceedings of the National Academy of Sciences of the United States of America. 100 (24): 13773–78. Bibcode:2003PNAS..10013773P. doi: 10.1073/pnas.2336088100 . PMC   283497 . PMID   14610274.
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