Identification and Characterization of the Doublesex Gene of Nasonia Oliveira, D.C.S.G.; Werren, J.H.; Verhulst, E.C.; Giebel, J

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Identification and Characterization of the Doublesex Gene of Nasonia Oliveira, D.C.S.G.; Werren, J.H.; Verhulst, E.C.; Giebel, J University of Groningen Identification and characterization of the doublesex gene of Nasonia Oliveira, D.C.S.G.; Werren, J.H.; Verhulst, E.C.; Giebel, J. D.; Kamping, A.; Beukeboom, L. W.; van de Zande, L. Published in: Insect Molecular Biology DOI: 10.1111/j.1365-2583.2009.00874.x IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2009 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Oliveira, D. C. S. G., Werren, J. H., Verhulst, E. C., Giebel, J. D., Kamping, A., Beukeboom, L. W., & van de Zande, L. (2009). Identification and characterization of the doublesex gene of Nasonia. Insect Molecular Biology, 18(3), 315-324. https://doi.org/10.1111/j.1365-2583.2009.00874.x Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 01-10-2021 Insect Molecular Biology (2009) 18(3), 315–324 doi: 10.1111/j.1365-2583.2009.00874.x IdentificationBlackwell Publishing Ltd and characterization of the doublesex gene of Nasonia D. C. S. G. Oliveira*‡, J. H. Werren*, E. C. Verhulst†, (Baker & Wolfner, 1988). Differential splicing of male and J. D. Giebel*§, A. Kamping†, L. W. Beukeboom† female dsx mRNA results in sex-specific dsx proteins, which and L. van de Zande† regulate downstream somatic sexual dimorphism (Baker & *Department of Biology, University of Rochester, Wolfner, 1988). The dsx protein is characterized by two Rochester, NY, USA; and †Evolutionary Genetics, Centre functional domains, an N-terminal DNA binding domain for Ecological and Evolutionary Studies, University of (DM domain or OD1) and a C-terminal dimerization domain Groningen, Haren, The Netherlands (dsx dimer or OD2). The DM domain is a zinc module, with conserved amino acid residues for zinc chelating and promoter binding (Zhu et al., 2000). The dsx dimer is an alpha-helical Abstract motif which, by promoting dimerization of dsx, enhances The doublesex (dsx) gene of the parasitic wasp DNA recognition by the DM domain (Bayrer et al., 2005). Nasonia vitripennis is described and characterized. Strong conservation of the DM domain occurs between Differential splicing of dsx transcripts has been shown D. melanogaster dsx (DMdsx) and the sex determining to induce somatic sexual differentiation in Diptera and protein mab-3 in the nematode Caenorhabditis elegans. Lepidoptera, but not yet in other insect orders. Two Function of the gene in these divergent organisms is spliceforms of Nasonia dsx mRNA are differentially sufficiently conserved that DMdsx can partially rescue expressed in males and females. In addition, in a male-specific development in mab-3 deficient worms gynandromorphic line that produces haploids (normally (Raymond et al., 1998). Furthermore, the mammalian Dmrt- males) with full female phenotypes, these individuals 1 gene transcribes a DM domain protein that is differentially show the female spliceform, providing the first demon- expressed in testes, and mutations in this gene suggest stration of a direct association of dsx with somatic sex that it plays an important role in male sexual differentiation differentiation in Hymenoptera. Finally, the DNA binding (Raymond et al., 2000). Recently, dsx orthologues have (DM) domain of Nasonia dsx clusters phylogenetically been detected in a variety of insects. Doublesex orthologues with dsx from other insects, and Nasonia dsx shows have most extensively been described in Diptera, including microsynteny with dsx of Apis, further supporting Anastrepha obliqua (Ruiz et al., 2005), Anopheles gambiae identification of the dsx orthologue in Nasonia. (Scali et al., 2005), Bactrocera tryoni (Sherman & Frommer, 1998) and Musca domestica (Hediger et al., 2004), but also Keywords: DM domain genes, doublesex, haplodiploidy, have been found in Lepidoptera (Bombyx mori, Ohbayashi Hymenoptera, sex determination. et al., 2001) and Hymenoptera (Apis mellifera; Cho et al., 2007), as all have a characteristic strongly conserved DM Introduction domain. However, in only a few cases have spliceform differences between males and females been shown, eg in The role of the transcription factor doublesex (dsx) in sex Ap. mellifera (Cho et al., 2007) and functional assays are determination was first described in Drosophila melanogaster restricted to Drosophila (eg Baker & Wolfner, 1988; Raymond et al., 1998) and to a lesser extent to Lepidoptera First published online 23 March 2009. (Suzuki et al., 2005). A current hypothesis predicts higher Correspondence: John W. Werren, 306 Hutchinson Hall, Department of conservation at the base of sex-determining gene cascades, Biology, University of Rochester, Rochester, NY 14627, USA. Tel.: +1 585 ie dsx, but divergence at the level of upstream primary 275 3889; fax: +1 585 275 2070; e-mail: [email protected]. signals (Wilkins, 1995). Present addresses: ‡Departament de Genètica i de Microbiologia, Hymenoptera, including the honeybee Ap. mellifera and Universitat Autònoma de Barcelona, Bellaterra, Spain; and §Department of Microbiology and Immunology, University of Michigan Medical School, Ann the jewel wasp Nasonia, have haplodiploid sex determination. Arbor, MI, USA. Males are haploid and develop parthenogenetically from © 2009 The Authors Journal compilation © 2009 The Royal Entomological Society 315 316 D. C. S. G. Oliveira et al. unfertilized eggs, whereas females are diploid and develop morphological sex-specific differences amongst Nasonia from fertilized eggs. For over 60 years it has been known species (J. H. Werren et al., unpubl. data). The putative that different sex-determining mechanisms exist within the coding region of this gene, provisionally termed DM1, was Hymenoptera (Whiting, 1943). In haplodiploids, a relatively represented in a fully sequenced bacterial artificial common mechanism is complementary sex determination chromosome of Nasonia giraulti (NG, GenBank accession (CSD). Gender is genetically determined by a single locus number AC185330). Subsequently, the N. vitripennis (NV) with multiple alleles: individuals that are heterozygous at genome was bioinformatically screened with the DM domain- this locus develop into females, whereas hemizygotes and coding sequence and, in addition to finding the NV DM1, homozygotes develop into haploid and diploid males, three additional DM-domain genes were detected, termed respectively (Whiting, 1943; Crozier, 1971). This mode of DM2, DM3 and DM4. These four DM domain-containing sex determination has now been shown for more than 60 genes were found in the following scaffolds: DM1, scaffold species (van Wilgenburg et al., 2006) and for the honeybee 23; DM2, scaffold 53; DM3, scaffold 62; DM4, scaffold 6 the complementary sex determiner (csd) gene was (NV genome version 1.0; HGSC at Baylor College of Medicine). identified and cloned (Beye et al., 2003). However, it is clear Besides giving the strongest BLAST match to any insect dsx that sex determination in some groups, such as the large genes, the DM1 gene also contains a second conserved parasitoid wasp group Chalcidoidea to which Nasonia coding sequence characteristic of dsx proteins: the dsx belongs, cannot be explained by CSD, because upon dimerization domain (dsx dimer). Only one gene containing inbreeding homozygous diploids still develop into females the dsx dimer was found in each of the five insect genomes (Skinner & Werren, 1980). searched (see below). Further analysis of scaffold 23, involving The parasitic wasp Nasonia has been extensively the immediate flanking sequences of DM1 revealed that studied genetically and is rapidly being recognized as a the DM1 is flanked upstream by a prospero orthologue and model system in evolutionary and developmental biology downstream by an elongase gene (data not shown). (Werren & Stouthamer, 2002; Shuker et al., 2003; Pultz & Microsynteny of prospero – dsx gene order is also present Leaf, 2003; Beukeboom & Desplan, 2003; Werren et al., in the genomes of Ap. mellifera, Tribolium castaneum and 2004; Ferree et al., 2006; Lynch et al., 2006). It has been An. gambiae, but not in D. melanogaster. known for a long time that its sex determination is not Four different DM-domain genes were also found in the governed by CSD (Whiting, 1967; Skinner & Werren, 1980), genomes of D. melanogaster and Ap. mellifera, whereas but until recently little progress had been made in elucidating only three were found in the genomes of T. castaneum and its mode of sex determination (Beukeboom, 1995). Recently, An. gambiae. Phylogenetic analysis using
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