A small molecule for a big transformation: topical application of a 20-nucleotide-long antisense fragment of the DIAP-2 gene inhibits the development of Drosophila melanogaster female imagos

Palmah M. Nyadar, Volodymyr V. Oberemok, Ilya V. Zubarev


Several genes have been identified to play important roles associated with sex selection in Drosophila melanogaster. An essential part is attributed to the sex-lethal gene that depends on the expression of the X:A (number of chromosomes to autosomes) ratio signal controlling both sex selection and dosage compensation processes in D. melanogaster. Interestingly, for sex selection in D. melanogaster there are no documented data addressing the role of the inhibitor of apoptosis (IAP) genes and their signaling influence on this biological process. In this study, we found that topical application of a 20-nucleotide-long antisense DNA fragment (oligoDIAP-2) from the death-associated inhibitor of apoptosis (DIAP)-2 gene interferes with D. melanogaster development and significantly decreases the number of female imagos and their biomass. We show that the applied antisense oligoDIAP-2 fragment downregulates the target DIAP-2 gene whose normal concentration is necessary for the development of female D. melanogaster. These data correspond to the results on downregulation of the target host IAP-Z gene of Lymantria dispar L. female imagos after topical treatment with an 18-nucleotide-long antisense DNA fragment from the Lymantria dispar multicapsid nuclear polyhedrosis virus IAP-3 gene at the larval stage. The observed novel phenomenon linking the downregulation of insect IAP genes and the low rate of female imago development could have practical application, especially in insect pest control and molecular pathology.


Received: March 2, 2017; Revised: April 29, 2017; Accepted: May 17, 2017; Published online: July 19, 2017

How to cite this article: Nyadar PM, Oberemok VV, Zubarev IV. A small molecule for a big transformation: Topical application of a 20-nucleotide-long antisense fragment of the DIAP-2 gene inhibits the development of Drosophila melanogaster female imagos. Arch Biol Sci. 2018;70(1):33-9.


inhibitor of apoptosis (IAP) genes; Drosophila melanogaster DIAP-2 gene; sex determination; developmental biology; DNA insecticides

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Hay BA, Huh JR, Guo M. The genetics of cell death: approaches, insights and opportunities in Drosophila. Nature Rev Genet. 2004;5(12):911-22.

Vucic D, Kaiser WJ, Harvey AJ, Miller LK. Inhibition of reaper-induced apoptosis by interaction with inhibitor of apoptosis proteins (IAPs). Proc Natl Acad Sci. 1997;94(19):10183-4.

Leulier F, Lhocine N, Lemaitre B, Meier P. The Drosophila inhibitor of apoptosis protein DIAP2 functions in innate immunity and is essential to resist gram-negative bacterial infection. Mol Cell Biol. 2006;26(21):7821-31.

Huh JR, Foe I, Muro I, Chen CH, Seol JH, Yoo SJ, Guo M, Park JM, Hay BA. The Drosophila inhibitor of apoptosis (IAP) DIAP2 is dispensable for cell survival, required for the innate immune response to gram-negative bacterial infection, and can be negatively regulated by the reaper/hid/grim family of IAP-binding apoptosis inducers. J Biol Chem. 2007;282(3):2056-68.

Bergmann A. The role of ubiquitylation for the control of cell death in Drosophila. Cell Death Differ. 2010;17(1):61-7.

Rumble JM, Duckett CS. Diverse functions within the IAP family. J Cell Sci. 2008;121(21):3505-7.

Cline TW. Evidence that sisterless-a and sisterless-b are two of several discrete" numerator elements" of the X/A sex determination signal in Drosophila that switch Sxl between two alternative stable expression states. Genetics. 1988;119(4):829-62.

Salz H, Erickson JW. Sex determination in Drosophila: The view from the top. Fly. 2010;4(1):60-70.

Mullon C, Pomiankowski A, Reuter M. Molecular evolution of Drosophila Sex-lethal and related sex determining genes. BMC Evol Biol. 2012;12(1):5.

Oberemok VV, Skorokhod OA. Single-stranded DNA fragments of insect-specific nuclear polyhedrosis virus act as selective DNA insecticides for gypsy moth control. Pest Biochem Physiol. 2014;113:1-7.

Oberemok VV, Laikova KV, Zaitsev AS, Nyadar PM, Shumskykh MN, Gninenko Yu I. DNA insecticides based on iap3 gene fragments of cabbage looper and gypsy moth nuclear polyhedrosis viruses show selectivity for non-target insects. Arch Biol Sci. 2015;67(3):785-92.

Oberemok VV, Laikova KV, Zaitsev AS, Gushchin VA, Skorokhod OA. The RING for gypsy moth control: topical application of fragment of its nuclear polyhedrosis virus anti-apoptosis gene as insecticide. Pest Biochem Physiol. 2016;131:32-9.

Nyadar PM, Zaitsev AS, Tajudeen AA, Shumskykh MN, Oberemok VV. Biological control of gypsy moth (Lymantria dispar): an RNAi-based approach and a case for DNA insecticides. Arch Biol Sci. 2016;68(3):677-83.

Dias N, Stein CA. Antisense oligonucleotides: basic concepts and mechanisms. Mol Cancer Ther. 2002;1(5):347-55.

Raymond CS, Shamu CE, Shen MM, Seifert KJ, Hirsch B, Hodgkin J, Zarkower D. Evidence for evolutionary conservation of sex-determining genes. Nature. 1998;391(6668):691-95.

Bangs P, White K. Regulation and execution of apoptosis during Drosophila development. Dev Dynam. 2000;218(1):68-79.

Hay BA. Understanding IAP function and regulation: a view from Drosophila. Cell Death Differ. 2000;7(11):1045-56.

Abdelwahid E, Yokokura T, Krieser RJ, Balasundaram S, Fowle WH, White K. Mitochondrial disruption in Drosophila apoptosis. Dev Cell. 2007;12(5):793-806.

Griffiths AJ. An introduction to genetic analysis. Macmillan. 2005.

Arbeitman MN, New F, Fear JM, Howard TS, Dalton JE, Graze RM. Sex Differences in Drosophila Somatic Gene Expression: Variation and Regulation by Doublesex. G3 (Bethesda). 2016;6(7):1799-808.

Cheng C, Kirkpatrick M. Sex-Specific Selection and Sex-Biased Gene Expression in Humans and Flies. PLoS Genet. 2016;12(9):e1006170.

Richardson LA. Sex Chromosomes Do It Differently. PLoS Biol. 2016;14(10):e2001096.

Edward DA, Chapman T. Sex‐specific effects of developmental environment on reproductive trait expression in Drosophila melanogaster. Ecol Evol. 2012;2(7):1362-70.

Bopp D, Bell LR, Cline TW, Schedl P. Developmental distribution of female-specific Sex-lethal proteins in Drosophila melanogaster. Genes Dev. 1991;5(3):403-15.

Van Doorn GS. Patterns and mechanisms of evolutionary transitions between genetic sex-determining systems. Cold Spring Harb Perspect Biol. 2014;6(8):a017681.

Gupta P.K. Genetics. 3rd ed. New Delhi: Capital Offset Press; 2008-9. 534 p.

Oberemok VV, Nyadar PM. Investigation of mode of action of DNA insecticides on the basis of LdMNPV IAP-3 gene. Turk J Biol. 2015; 39(2):258-64.

Oberemok VV, Laikova KV, Zaitsev AS, Nyadar PM, Gninenko YuI, Gushchin VA, Makarov VV, Agranovsky AA.Topical treatment of LdMNPV-infected gypsy moth larvae with 18 nucleotides long antisense fragment from LdMNPV IAP-3 gene triggers higher level of apoptosis in the infected cells and mortality of the pest. J Plant Prot Res. 2017; 57 (1):18-24.

Ghiselli F, Milani L, Chang PL, Hedgecock D, Davis JP, Nuzhdin, SV, Passamonti M. De novo assembly of the Manila clam Ruditapes philippinarum transcriptome provides new insights into expression bias, mitochondrial doubly uniparental inheritance and sex determination. Mol Biol Evol. 2012;29:771-86.

Oberemok VV, Laikova KV, Gninenko YI, Zaitsev AS, Nyadar PM, Adeyemi TA. A short history of insecticides. J Plant Prot Res. 2015;55(3):221-6.


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