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Журнальные статьи

Akagi, Kazutaka; Kageyama, Yuji; Kayashima, Yasunari; et al. The Binding of Multiple Nuclear Receptors to a Single Regulatory Region Is Important for the Proper Expression of EDG84A in Drosophila melanogaster //JOURNAL OF MOLECULAR BIOLOGY Volume: 425 Issue: 1 Pages: 71-81 JAN 9 2013

Nuclear receptor transcription factor family members share target sequence similarity; however, little is known about how these factors exert their specific regulatory control. Here, we examine the mechanism regulating the expression of the Drosophila EDG84A gene, a target gene of the orphan nuclear receptor beta FTZ-F1, as a model to study the cooperative behavior among nuclear receptors. We show that the three nuclear receptors beta FTZ-F1, DHR3, and DHR39 bind to a common element in the EDG84A promoter. The expression level of the EDG84A promoter-lacZ reporter genes in DHR39-induced and mutant animals, respectively, suggests that DHR39 works as a repressor. The activity of a reporter gene carrying a mutation preventing DHR3 binding was reduced in ftz-f1 mutants and rescued by the induced expression of beta FTZ-F1, suggesting that DHR3 and beta FTZ-F1 activate the EDG84A gene in a redundant manner. A reporter gene carrying a mutation that abolishes DHR39 and FTZ-F1 binding was prematurely expressed, and the expression level of the reporter gene carrying a mutation preventing DHR3 binding was reduced. These findings suggest that the temporal expression of this gene is mainly controlled by beta FTZ-F1 but that the binding of DHR3 is also important. Comparison of the binding site sequence among Drosophila species suggests that DHR3 binding ability was gained after the melanogastersubgroup evolved, and this ability may contribute to the robust expression of this gene. These results show the complicated regulatory mechanisms utilized by multiple nuclear receptors to properly regulate the expression of their target gene through a single target site.

Akif, Mohd; Georgiadis, Dimitris; Mahajan, Aman; et al. High-Resolution Crystal Structures of Drosophila melanogaster Angiotensin-Converting Enzyme in Complex with Novel Inhibitors and Antihypertensive Drugs //JOURNAL OF MOLECULAR BIOLOGY Volume: 400 Issue: 3 Pages: 502-517 JUL 16 2010

Angiotensin I-converting enzyme (ACE), one of the central components of the renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N and C). The N- and C-domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting both domains leading to defects in other pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homologue from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study, we present high-resolution structures for native AnCE and in complex with six known antihypertensive drugs, a novel C-domain sACE specific inhibitor, lisW-S, and two sACE domain-specific phosphinic peptidyl inhibitors, RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side chains at different binding pockets in the active site in comparison with the active site of N- and C-domains of sACE. This study provides information about the structure-activity relationships that could be utilized for designing new inhibitors with improved domain selectivity for sACE

Akif, Mohd; Ntai, Ioanna; Sturrock, Edward D.; et al. Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 398 Issue: 3 Pages: 532-536 JUL 30 2010

Angiotensin-I converting enzyme (ACE, a zinc dependent dipeptidyl carboxypeptidase) is a major target of drugs due to its role in the modulation of blood pressure and cardiovascular disorders. Here we present a crystal structure of AnCE (an ACE homologue from Drosophila melanogaster with a single enzymatic domain) in complex with a natural product-phosphonotripeptide. K-26 at 1.96 angstrom resolution. The inhibitor binds exclusively in the S(1) and S(2) binding pockets of AnCE (coordinating the zinc ion) through ionic and hydrogen bond interactions. A detailed structural comparison of AnCE-K-26 complex with individual domains of human somatic ACE provides useful information for further exploration of ACE inhibitor pharmacophores involving phosphonic acids.

Bonilla-Ramirez, Leonardo; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos Low doses of paraquat and polyphenols prolong life span and locomotor activity in knock-down parkin Drosophila melanogaster exposed to oxidative stress stimuli: Implication in autosomal recessive juvenile Parkinsonism //GENE Volume: 512 Issue: 2 Pages: 355-363 JAN 10 2013

Previous studies have shown that polyphenols might be potent neuroprotective agents in Drosophila melanogaster wild type Canton-S acutely or chronically treated with paraquat (PQ), a selective toxin for elimination of dopaminergic (DAergic) neurons by oxidative stress (OS), as model of Parkinson's disease (PD). This study reports for the first time that knock-down (K-D) parkin Drosophila melanogaster (TH-GAL4; UAS-RNAi-parkin) chronically exposed to PQ (0.1-0.25 mM), FeSO4 (Fe, 0.1 mM), deferoxamine (DFO, 0.01 mM) alone or (0.1 mM) PQ in combination with polyphenols propyl gallate (PG, 0.1 mM) and epigallocathecin gallate (EGCG, 0.1, 0.5 mM) showed significantly higher life span and locomotor activity than untreated K-D flies or treated with (1, 5, 20 mM) PQ alone. Whilst gallic acid (GA, 0.1, 0.5 mM) alone or in the presence of PQ provoked no effect on K-D flies, epicathecin (EC, 0.5 mM) only showed a positive effect on prolonging K-D flies' life span. It is shown that PG (and EGCG) protected protocerebral posterolateral 1 (PPL1) DAergic neurons against PQ. Interestingly, the protective effect of low PQ concentrations, DFO and iron might be explained by a phenomenon known as "hormesis." However, pre-fed K-D flies with (0.1 mM) PQ for 7 days and then exposed to (0.25 mM) for additional 8 days affect neither survival nor climbing of K-D Drosophila compared to flies treated with (0.25 mM) PQ alone. Remarkably, K-D flies treated with 0.1 mM PQ (7 days) and then with (0.25 mM) PQ plus PG (8 days) behaved almost as flies treated with (0.25 mM) PQ. Taken these data suggest that antioxidant supplements that synergistically act with low pro-oxidant stimuli to prolong and increase locomotor activity become inefficient once a threshold of OS has been reached in K-D flies. Our present findings support the notion that genetically altered Drosophila melanogaster as suitable model to study genetic and environmental factors as causal and/or modulators in the development of autosomal recessive juvenile Parkinsonism (AR-JD)/PD. Most importantly, we have shown for the first time that low amounts of stressors induce a health-promoting extending effect in K-D parkin flies. Altogether our present results open new avenues for the screening, testing and development of novel antioxidant drugs against OS stimuli in neurodegenerative disorders.

Cohen, Lior; Moran, Yehu; Sharon, Amir; et al. Drosomycin, an Innate Immunity Peptide of Drosophila melanogaster, Interacts with the Fly Voltage-gated Sodium Channel //JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 284 Issue: 35 Pages: 23558-23563 AUG 28 2009

Several peptide families, including insect antimicrobial peptides, plant protease inhibitors, and ion channel gating modifiers, as well as blockers from scorpions, bear a common CS alpha beta scaffold. The high structural similarity between two peptides containing this scaffold, drosomycin and a truncated scorpion beta-toxin, has prompted us to examine and compare their biological effects. Drosomycin is the most expressed antimicrobial peptide in Drosophila melanogaster immune response. A truncated scorpion beta-toxin is capable of binding and inducing conformational alteration of voltage-gated sodium channels. Here, we show that both peptides (i) exhibit anti-fungal activity at micromolar concentrations; (ii) enhance allosterically at nano-molar concentration the activity of Lqh alpha IT, a scorpion alpha toxin that modulates the inactivation of the D. melanogaster voltage-gated sodium channel (DmNa(v)1); and ( iii) inhibit the facilitating effect of the polyether brevetoxin-2 on DmNa(v)1 activation. Thus, the short CS alpha beta scaffold of drosomycin and the truncated scorpion toxin can maintain more than one bioactivity, and, in light of this new observation, we suggest that the biological role of peptides bearing this scaffold should be carefully examined. As for drosomycin, we discuss the intriguing possibility that it has additional functions in the fly, as implied by its tight interaction with DmNa(v)1.

Costa, Elisabet; Beltran, Sergi; Espinas, M. Lluisa Drosophila melanogaster SAP18 protein is required for environmental stress responses //FEBS LETTERS Volume: 585 Issue: 2 Pages: 275-280 JAN 21 2011

SAP18, a highly evolutionarily conserved protein, has been proposed to be involved in multiple cellular processes, from gene regulation to mRNA processing. To gain further insight into the role of SAP18, we performed genome-wide expression profiling of dsap18 mutant Drosophila melanogaster embryos and we found that dSAP18 is required for the expression of immune and stress related genes. We show that dSAP18 colocalizes with histone H3 phosphorylation, which has been implicated in the regulation of genes in response to signaling stimuli. dsap18 mutant larvae develop melanotic tumors after heat shock and the viability of dsap18 mutant flies is reduced after fungal infection or in high-salt medium. Altogether, our results indicate that dSAP18 is a key player in transcriptional responses to stress.

Costa, Rita; Speretta, Elena; Crowther, Damian C.; et al. Testing the Therapeutic Potential of Doxycycline in a Drosophila melanogaster Model of Alzheimer Disease //JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 286 Issue: 48 Pages: 41647-41655 DEC 2 2011

Therapies for Alzheimer disease that reduce the production of pathogenic amyloid beta (A beta) peptides have been associated with a range of unwanted effects. For this reason, alternative strategies that promote the clearance of the peptide by preventing its aggregation and deposition in the brain have been favored. In this context we have studied doxycycline, a member of the tetracycline family of antibiotics that has shown neuroprotective effects in a number of models of neurodegenerative disease. We investigated the neuroprotective potential of doxycycline in a Drosophila model of A beta toxicity and sought to correlate any effects with the aggregation state of the peptide. We found that administration of doxycycline to A beta 42-expressing flies did not improve their lifespan but was able to slow the progression of their locomotor deficits. We also measured the rough eye phenotype of transgenic flies expressing the E22G variant of A beta 42 and showed that doxycycline administration partially rescued the toxicity of A beta in the developing eye. We correlated these in vivo effects with in vitro observations using transmission electron microscopy, dynamic light scattering, and thioflavin T binding. We found that doxycycline prevents A beta fibrillization and favors the generation of smaller, non-amyloid structures that were nontoxic as determined by the lack of caspase 3 activation in a neuroblastoma cell line. Our confirmation that doxycycline can prevent amyloid beta toxicity both in vitro and in vivo supports its therapeutic potential in AD.


Precise estimates of costs and benefits, the fitness economics, of mating are of key importance in understanding how selection shapes the coevolution of male and female mating traits. However, fitness is difficult to define and quantify. Here, we used a novel application of an established analytical technique to calculate individual- and population-based estimates of fitness-including those sensitive to the timing of reproduction-to measure the effects on females of increased exposure to males. Drosophila melanogaster females were exposed to high and low frequencies of contact with males, and life-history traits for each individual female were recorded. We then compared different fitness estimates to determine which of them best described the changes in life histories. We predicted that rate-sensitive estimates would be more accurate, as mating influences the rate of offspring production in this species. The results supported this prediction. Increased exposure to males led to significantly decreased fitness within declining but not stable or increasing populations. There was a net benefit of increased male exposure in expanding populations, despite a significant decrease in lifespan. The study shows how a more accurate description of fitness, and new insights can be achieved by considering individual life-history strategies within the context of population growth.

Egorova, Ksenia S.; Olenkina, Oxana M.; Kibanov, Mikhail V.; et al. Genetically Derepressed Nucleoplasmic Stellate Protein in Spermatocytes of D. melanogaster Interacts with the Catalytic Subunit of Protein Kinase 2 and Carries Histone-Like Lysine-Methylated Mark //JOURNAL OF MOLECULAR BIOLOGY Volume: 389 Issue: 5 Pages: 895-906 JUN 26 2009

The X-chromosome-linked clusters of the tandemly repeated testis-specific Stellate genes of Drosophila melanogaster, encoding proteins homologous to the regulatory beta-subunit of the protein kinase casein kinase 2 (CK2), are repressed in wild-type males. Derepression of Stellate genes in the absence of the Y chromosome or Y-linked crystal locus (crystal line) causes accumulation of abundant protein crystals in testes and different meiotic abnormalities, which lead to partial or complete male sterility. To understand the cause of abnormalities in chromosome behavior owing to Stellate overexpression, we studied subcellular localization of Stellate proteins by biochemical fractionation and immunostaining of whole testes. We showed that, apart from the known accumulation of Stellate in crystalline form, soluble Stellate was located exclusively in the nucleoplasm, whereas Stellate crystals were located mainly in the cytoplasm. Coimmunoprecipitation experiments revealed that the alpha-subunit of the protein kinase CK2 (CK2 alpha) was associated with soluble Stellate. Interaction between soluble Stellate and CK2 alpha in the nucleus could lead to modulations in the phosphorylation of nuclear targets of CK2 and abnormalities in the meiotic segregation of chromosomes. We also observed that Stellate underwent lysine methylation and mimicked trimethyl-H3K9 epigenetic modification of histone.H3 tail.

Fukui, Tomokazu; Morishita, Suguru; Itoh, Masanobu. RNA editing and elimination of P element sequences in antisense read-through transcripts of Drosophila melanogaster //GENES & GENETIC SYSTEMS Volume: 84 Issue: 6 Pages: 440-440 DEC 2009

Gomez, Federico H.; Loeschcke, Volker; Norry, Fabian M. QTL for survival to UV-C radiation in Drosophila melanogaster //INTERNATIONAL JOURNAL OF RADIATION BIOLOGY Volume: 89 Issue: 7 Pages: 583-589 JUL 2013

Purpose : The aim of this study was to investigate tolerance to UV-C (ultraviolet C, 280-100 nm) radiation in Drosophila melanogaster, implementing a quantitative trait locus (QTL) mapping approach. This is of interest to test for genetic variation in survival to UV (ultraviolet) radiation. Materials and methods : We performed a QTL scan in D. melanogaster recombinant inbred lines (RIL) constructed from parental stocks derived from a crossing between northern and southern hemisphere populations that segregated substantial genetic variation in thermal resistance in a previous study. Here, two experimental treatments were implemented: Continuous and cyclic UV-C radiation. Results : Significant QTL were detected on all three major chromosomes. Among these, multiple trait composite interval mapping revealed a significant QTL in the pericentromeric region of chromosome 2, a genome region consistently implicated in thermotolerance in previous studies. Conclusions : This study shows substantial genetic variation for UV-C radiation resistance in D. melanogaster, with QTL for survival to UV-C radiation generally overlapping with major thermotolerance QTL. The genetic architecture of UV-C radiation resistance appears to be more complex in continuously irradiated individuals.

Goto, Shin G.; Udaka, Hiroko; Ueda, Chiaki; et al. Fatty acids of membrane phospholipids in Drosophila melanogaster lines showing rapid and slow recovery from chill coma //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 391 Issue: 2 Pages: 1251-1254 JAN 8 2010

We investigated the fatty acid compositions of phospholipids in Drosophila melanogaster lines showing rapid (CR), intermediate (CTL), or slow (CS) recovery from chill coma, which were established by artificial selection or by free recombination without selection. Compared to CTL, CS showed a low composition of dienoic acids and a small number of double bonds in the fatty acids. The ratio of unsaturated fatty acids and saturated fatty acids (UFAs/SFAs) was significantly lower in CS than in CTL. CR had higher monoenoic acid composition and lower dienoic acid composition than CTL. In addition, the amount of SFAs was lower and therefore the UFAs/SFAs ratio considerably higher in CR than in CTL. These changes in phospholipid fatty acids probably contributed to losing and maintaining the homeoviscosity of the cellular membranes in CS and CR, respectively, at low temperature and therefore produced their distinct phenotypes in recovery from chill coma.

Guzik-Lendrum, Stephanie; Nagy, Attila; Takagi, Yasuharu; et al. Drosophila melanogaster Myosin-18 Represents a Highly Divergent Motor with Actin Tethering Properties //JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 286 Issue: 24 Pages: 21755-21766 JUN 17 2011

The gene encoding Drosophila myosin-18 is complex and can potentially yield six alternatively spliced mRNAs. One of the major features of this myosin is an N-terminal PDZ domain that is included in some of the predicted alternatively spliced products. To explore the biochemical properties of this protein, we engineered two minimal motor domain (MMD)-like constructs, one that contains the N-terminal PDZ (myosin-18 M-PDZ) domain and one that does not (myosin-18 M-Delta PDZ). These two constructs were expressed in the baculovirus/Sf9 system. The results suggest that Drosophila myosin-18 is highly divergent from most other myosins in the superfamily. Neither of the MMD constructs had an actin-activated MgATPase activity, nor did they even bind ATP. Both myosin-18 M-PDZ and M-Delta PDZ proteins bound to actin with K-d values of 2.61 and 1.04 mu M, respectively, but only about 50-75% of the protein bound to actin even at high actin concentrations. Unbound proteins from these actin binding assays reiterated the 60% saturation maximum, suggesting an equilibrium between actin-binding and non-actin-binding conformations of Drosophila myosin-18 in vitro. Neither the binding affinity nor the substoichiometric binding was significantly affected by ATP. Optical trapping of single molecules in three-bead assays showed short lived interactions of the myosin-18 motors with actin filaments. Combined, these data suggest that this highly divergent motor may function as an actin tethering protein.

Han, Qian; Robinson, Howard; Li, Jianyong Biochemical identification and crystal structure of kynurenine formamidase from Drosophila melanogaster //BIOCHEMICAL JOURNAL Volume: 446 Pages: 253-260 Part: 2 SEP 1 2012

KFase (kynurenine formamidase), also known as arylformamidase and formylkynurenine formamidase, efficiently catalyses the hydrolysis of NFK (N-formyl-L-kynurenine) to kynurenine. KFase is the second enzyme in the kynurenine pathway of tryptophan metabolism. A number of intermediates formed in the kynurenine pathway are biologically active and implicated in an assortment of medical conditions, including cancer, schizophrenia and neurodegenerative diseases. Consequently, enzymes involved in the kynurenine pathway have been considered potential regulatory targets. In the present study, we report, for the first time, the biochemical characterization and crystal structures of Drosophila melanogaster KFase conjugated with an inhibitor, PMSF. The protein architecture of KFase reveals that it belongs to the alpha/beta hydrolase fold family. The PMSF-binding information of the solved conjugated crystal structure was used to obtain a KFase and NFK complex using molecular docking. The complex is useful for understanding the catalytic mechanism of KFase. The present study provides a molecular basis for future efforts in maintaining or regulating kynurenine metabolism through the molecular and biochemical regulation of KFase.

Hedges, Lauren M.; Yamada, Ryuichi; O'Neill, Scott L.; et al. The Small Interfering RNA Pathway Is Not Essential for Wolbachia-Mediated Antiviral Protection in Drosophila melanogaster //APPLIED AND ENVIRONMENTAL MICROBIOLOGY Volume: 78 Issue: 18 Pages: 6773-6776 SEP 2012

Wolbachia pipientis delays RNA virus-induced mortality in Drosophila spp. We investigated whether Wolbachia-mediated protection was dependent on the small interfering RNA (siRNA) pathway, a key antiviral defense. Compared to Wolbachia-free flies, virus-induced mortality was delayed in Wolbachia-infected flies with loss-of-function of siRNA pathway components, indicating that Wolbachia-mediated protection functions in the absence of the canonical siRNA pathway.


Populations of Drosophila melanogaster face significant mortality risks from parasitoid wasps that use species-specific strategies to locate and survive in hosts. We tested the hypothesis that parasitoids with different strategies select for alternative host defense characteristics and in doing so contribute to the maintenance of fitness variation and produce trade-offs among traits. We characterized defense traits of Drosophila when exposed to parasitoids with different host searching behaviors (Aphaereta sp. and Leptopilina boulardi). We used host larvae with different natural alleles of the gene Dopa decarboxylase (Ddc), a gene controlling the production of dopamine and known to influence the immune response against parasitoids. Previous population genetic analyses indicate that our focal alleles are maintained by balancing selection. Genotypes exhibited a trade-off between the immune response against Aphaereta sp. and the ability to avoid parasitism by L. boulardi. We also identified a trade-off between the ability to avoid parasitism by L. boulardi and larval competitive ability as indicated by differences in foraging and feeding behavior. Genotypes differed in dopamine levels potentially explaining variation in these traits. Our results highlight the potential role of parasitoid biodiversity on host fitness variation and implicate Ddc as an antagonistic pleiotropic locus influencing larval fitness traits.

Hung, Ko-Hsuan; Titus, Mitchell; Chiang, Shu-Chi; et al A Map of Drosophila melanogaster Small Nuclear RNA-activating Protein Complex (DmSNAPc) Domains Involved in Subunit Assembly and DNA Binding //JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 284 Issue: 34 Pages: 22568-22579 AUG 21 2009

Transcription of genes coding for the small nuclear RNAs (snRNAs) is dependent upon a unique transcription factor known as the small nuclear RNA-activating protein complex (SNAPc). SNAPc binds to an essential proximal sequence element located about 40-65 base pairs upstream of the snRNA transcription start site. In the fruit fly Drosophila melanogaster, DmSNAPc contains three distinct polypeptides (DmSNAP190, DmSNAP50, and DmSNAP43) that are stably associated with each other and bind to the DNA as a complex. We have used mutational analysis to identify domains within each subunit that are involved in complex formation with the other two subunits in vivo. We have also identified domains in each subunit required for sequence-specific DNA binding. With one exception, domains required for subunit-subunit interactions lie in the most evolutionarily conserved regions of the proteins. However, DNA binding by DmSNAPc is dependent not only upon the conserved regions but is also highly dependent upon domains outside the conserved regions. Comparison with functional domains identified in human SNAPc indicates many parallels but also reveals significant differences in this ancient yet rapidly evolving system.

Kaun, Karla R.; Devineni, Anita V.; Heberlein, Ulrike. Drosophila melanogaster as a model to study drug addiction //HUMAN GENETICS Volume: 131 Issue: 6 Special Issue: SI Pages: 959-975 JUN 2012

Animal studies have been instrumental in providing knowledge about the molecular and neural mechanisms underlying drug addiction. Recently, the fruit fly Drosophila melanogaster has become a valuable system to model not only the acute stimulating and sedating effects of drugs but also their more complex rewarding properties. In this review, we describe the advantages of using the fly to study drug-related behavior, provide a brief overview of the behavioral assays used, and review the molecular mechanisms and neural circuits underlying drug-induced behavior in flies. Many of these mechanisms have been validated in mammals, suggesting that the fly is a useful model to understand the mechanisms underlying addiction.

Kawano, Takeshi; Shimoda, Masami; Matsumoto, Hitoshi; et al. Identification of a Gene, Desiccate, Contributing to Desiccation Resistance in Drosophila melanogaster //JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 285 Issue: 50 Pages: 38889-38897 DEC 2010

Suitable alterations in gene expression are believed to allow animals to survive drastic changes in environmental conditions. Drosophila melanogaster larvae cease eating and exit moist food to search for dry pupation sites after the foraging stage in what is known as the wandering stage. Although the behavioral change from foraging to wandering causes desiccation stress, the mechanism by which Drosophila larvae protect themselves from desiccation remains obscure. Here, we identified a gene, CG14686 (designated as Desiccate (Desi)), whose expression was elevated during the wandering stage. The Desi expression level was reversibly decreased by transferring wandering larvae to wet conditions and increased again by transferring them to dry conditions. Elevation of Desi expression was also observed in foraging larvae when they were placed in dry conditions. Desi encoded a 261-amino acid single-pass transmembrane protein with notable motifs, such as SH2 and PDZ domain-binding motifs and a cAMP-dependent protein kinase phosphorylation motif, in the cytoplasmic region, and its expression was observed mainly in the epidermal cells of the larval integuments. Overexpression of Desi slightly increased the larval resistance to desiccation stress during the second instar. Furthermore, Desi RNAi larvae lost more weight under dry conditions, and subsequently, their mortalities significantly increased compared with control larvae. Under dry conditions, consumption of carbohydrate was much higher in Desi RNAi larvae than control larvae. Based on these results, it is reasonable to conclude that Desi contributes to the resistance of Drosophila larvae to desiccation stress.

Kayashima, Yasunari; Yamanashi, Keiko; Sato, Ayaka; et al. Freeze-Dried Royal Jelly Maintains Its Developmental and Physiological Bioactivity in Drosophila melanogaster //BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY Volume: 76 Issue: 11 Pages: 2107-2111 NOV 2012

Royal jelly (RJ), a honeybee-derived product, has been found to possess developmental and physiological bioactivity in the fruit fly, Drosophila melanogaster, but little is known about the in vivo bioactivity of freeze-dried RJ (FDRJ) powder, which is another form of RJ processed for human use. To address this, we used Drosophila as a model animal to examine the effects of FDRJ in multicellular organisms. When flies were reared on food supplemented with FDRJ, the developmental time from larva to adult was shortened, the adult male lifespan was prolonged, and female fecundity was increased without any significant morphological alterations. Moreover, the expression of dilp5, an insulin-like peptide, its receptor InR, and the nutrient sensing molecule TOR, the target of rapamycin, was significantly increased in FDRJ-fed female flies as compared with ones reared on standard and on protein-enriched food. These findings suggest that like RJ, FDRJ maintains its bioactivity even after processing from RJ, what is expected to have bioactivity for multicellular organisms, including humans.


Latitudinal clines in quantitative traits are common, but surprisingly little is known about the genetic bases of these divergences and how they vary within and between clines. Here, we use line-cross analysis to investigate the genetic architecture of wing size divergences at varying spatial scales along a body size cline in Drosophila melanogaster. Our results revealed that divergences in wing size along the cline were due to strong additive effects. Significant nonadditive genetic effects, including epistasis and maternal effects, were also detected, but they were relatively minor in comparison to the additive effects and none were common to all crosses. There was no evidence of increased epistasis in crosses between more geographically distant populations and, unlike in previous studies, we found no significant dominance effects on wing size in any cross. Our results suggest there is little variation in the genetic control of wing size along the length of the Australian cline. They also highlight marked inconsistencies in the magnitude of dominance effects across studies, which may reflect different opportunities for mutation accumulation while lines are in laboratory culture.

Khurana, Jaspreet S.; Wang, Jie; Xu, Jia; et al. Adaptation to P Element Transposon Invasion in Drosophila melanogaster //CELL Volume: 147 Issue: 7 Pages: 1551-1563 DEC 23 2011

Transposons evolve rapidly and can mobilize and trigger genetic instability. Piwi-interacting RNAs (piRNAs) silence these genome pathogens, but it is unclear how the piRNA pathway adapts to invasion of new transposons. In Drosophila, piRNAs are encoded by heterochromatic clusters and maternally deposited in the embryo. Paternally inherited P element transposons thus escape silencing and trigger a hybrid sterility syndrome termed P-M hybrid dysgenesis. We show that P-M hybrid dysgenesis activates both P elements and resident transposons and disrupts the piRNA biogenesis machinery. As dysgenic hybrids age, however, fertility is restored, P elements are silenced, and P element piRNAs are produced de novo. In addition, the piRNA biogenesis machinery assembles, and resident elements are silenced. Significantly, resident transposons insert into piRNA clusters, and these new insertions are transmitted to progeny, produce novel piRNAs, and are associated with reduced transposition. P element invasion thus triggers heritable changes in genome structure that appear to enhance transposon silencing.

Kim, Eun-Kyoung; Kim, Sung-Hee; Nam, Hyuck-Jin; et al. Draft Genome Sequence of Commensalibacter intestini A911(T), a Symbiotic Bacterium Isolated from Drosophila melanogaster Intestine //JOURNAL OF BACTERIOLOGY Volume: 194 Issue: 5 Pages: 1246-1246 MAR 2012

Commensalibacter intestini A911(T), a predominant symbiotic bacterium capable of stably colonizing gut epithelia, was isolated from the fruit fly, Drosophila melanogaster. Here we report the draft genome sequence of Commensalibacter intestini A911(T).

Kim, Heuijong; Kim, Kiyoung; Kim, Jaekwang; et al. Mutagenesis by imprecise excision of the piggyBac transposon in Drosophila melanogaster //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 417 Issue: 1 Pages: 335-339 JAN 6 2012

Mutagenesis by transposon-mediated imprecise excision is the most extensively used technique for mutagenesis in Drosophila. Although P-element is the most widely used transposon in Drosophila to generate deletion mutants, it is limited by the insertion coldspots in the genome where P-elements are rarely found. The piggyBac transposon was developed as an alternative mutagenic vector for mutagenesis of non-P-element targeted genes in Drosophila because the piggyBac transposon can more randomly integrate into the genome. Previous studies suggested that the piggyBac transposon always excises precisely from the insertion site without initiating a deletion or leaving behind an additional footprint. This unique characteristic of the piggyBac transposon facilitates reversible gene-transfer in several studies, such as the generation of induced pluripotent stem (iPS) cells from fibroblasts. However, it also raised a potential limitation of its utility in generating deletion mutants in Drosophila. In this study, we report multiple imprecise excisions of the piggyBac transposon at the sepia pterin reductase (SR) locus in Drosophila. Through imprecise excision of the piggyBac transposon inserted in the 5'-UTR of the SR gene, we generated a hypomorphic mutant allele of the SR gene which showed markedly decreased levels of SR expression. Our finding suggests that it is possible to generate deletion mutants by piggyBac transposon-mediated imprecise excision in Drosophila. However, it also suggests a limitation of piggyBac transposon-mediated reversible gene transfer for the generation of induced pluripotent stem (iPS) cells.

Knecht, Wolfgang; Mikkelsen, Nils Egil; Clausen, Anders Ranegaard; et al.Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 382 Issue: 2 Pages: 430-433 MAY 1 2009

Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) can additionally sensitize human cancer cell lines towards the anti-cancer drug gemcitabine. We show that this property is based on the Dm-dNK ability to efficiently phosphorylate gemcitabine. The 2.2 angstrom resolution structure of DmdNK in complex with gemcitabine shows that the residues Tyr70 and Arg105 play a crucial role in the firm positioning of gemcitabine by extra interactions made by the fluoride atoms. This explains why gemcitabine is a good substrate for Dm-dNK

Knowles, Aileen F. The single NTPase gene of Drosophila melanogaster encodes an intracellular nucleoside triphosphate diphosphohydrolase 6 (NTPDase6) //ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS Volume: 484 Issue: 1 Pages: 70-79 APR 1 2009

I report here the cloning and characterization of a nucleoside triphosphate diphosphohydrolase 6 (NTP-Dase6) encoded by the single Dmet/NTPase gene of Drosophila melanogaster. S2 cells stably transfected with the Drosophila NTPDase6 cDNA displayed strong UDPase activity only after addition of NP-40, indicating the intracellular location of the enzyme. The enzyme hydrolyzed UDP, GDP, and IDP equally well whereas other NDP and NTP were poor substrates. It was not or only partially inhibited by several modulators of the cell surface NTPDases, but was strongly inhibited upon oxidative cross-linking by copper phenanthroline. The decrease of activity correlated with dimer formation. Mutagenesis studies indicated that dimer formation required C42 in the transmembrane domain and C447 in the exoplasmic domain. Fluorescence microscopy revealed that the protein was located primarily in the ER. The substrate specificity and cellular localization of the Drosophila NTPDase6 suggest that it participates in Drosophila glycoprotein processing.


Substantial genetic variation exists in natural populations of Drosophila melanogaster. This segregating variation includes alleles at different loci that interact to cause lethality or sterility (synthetic incompatibilities). Fitness epistasis in natural populations has important implications for speciation and the rate of adaptive evolution. To assess the prevalence of epistatic fitness interactions, we placed naturally occurring X chromosomes into genetic backgrounds derived from different geographic locations. Considerable amounts of synthetic incompatibilities were observed between X chromosomes and autosomes: greater than 44% of all combinations were either lethal or sterile. Sex-specific lethality and sterility were also tested to determine whether Haldane's rule holds for within-species variation. Surprisingly, we observed an excess of female sterility in genotypes that were homozygous, but not heterozygous, for the X chromosome. The recessive nature of these incompatibilities is similar to that predicted for incompatibilities underlying Haldane's rule. Our study also found higher levels of sterility and lethality for genomes that contain chromosomes from different geographical regions. These findings are consistent with the view that genomes are coadapted gene complexes and that geography affects the likelihood of epistatic fitness interactions.

Lee, Kyu-Sun; Hong, Seung-Hyun; Kim, Ae-Kyeong; et al. Processed short neuropeptide F peptides regulate growth through the ERK-insulin pathway in Drosophila melanogaster //FEBS LETTERS Volume: 583 Issue: 15 Pages: 2573-2577 AUG 6 2009

The Drosophila sNPF gene regulates growth through the ERK-insulin pathway. sNPF encodes a precursor protein that is processed and produces biologically active sNPF peptides. However, the functions of these peptides are not known. In Drosophila neuronal cells in culture and in flies in vivo, sNPF1 and sNPF2 activated the ERK-insulin pathway and regulated body growth. In addition, the sNPF precursor and the processed sNPF peptide were co-localized in the neurons of the central nervous system. These results indicate that sNPF1 and sNPF2 peptides processed from the sNPF precursor are sufficient for regulating body growth through the ERK-insulin pathway in Drosophila.

Lee, Young-Nam; Shim, Young-Jun; Kang, Byeong-Ho; et al. Over-expression of human clusterin increases stress resistance and extends lifespan in Drosophila melanogaster //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 420 Issue: 4 Pages: 851-856 APR 20 2012

Clusterin is a disulfide-linked heterodimeric glycoprotein that has been implicated in a variety of biological processes. Its expression has been shown to be elevated during cellular senescence and normal aging, but it is uncertain whether clusterin protects against aging or whether its expression is a consequence of aging. To investigate the functions of clusterin during organismal aging, we established transgenic Drosophila alleles to induce the expression of the secretory form of human clusterin (hClu(S)) using the Gal4/UAS system. hClu(S) protein (similar to 60 kDa) was detected in both adult homogenates and larval hemolymphs of flies ubiquitously overexpressing hClu(S) (da-Gal4 > UAS-hClu(S)) and in motoneurons (D42-Gal4 > UAS-hClu(S)). Interestingly, the mean lifespans of these hClu(S)-overexpressing flies were significantly greater than those of control flies that exhibited no hClu(S) induction. hClu(S)-overexpressing flies also showed significantly greater tolerance to heat shock, wet starvation, and oxidative stress. Furthermore, amounts of reactive oxygen species (ROS) in whole bodies were significantly lower in hClu(S)-overexpressing flies. In addition, clusterin was found to prevent the inactivation of glutamine synthetase (GS) by metal-catalyzed oxidation (MCO) in vitro, and this protection was only supported by thiol-reducing equivalents, such as, DTT or GSH, and not by ascorbate (a non-thiol MCO system). Furthermore, this protection against GS inactivation by clusterin was abolished by reacting clusterin with N-ethylmaleimide, a sulfhydryl group-modifying agent. Taken together, these results suggest that a disulfide-linked form of clusterin functions as an antioxidant protein via its cysteine sulfhydryl groups to reduce ROS levels and delay the organismal aging in fruit flies.

Li XinHai; Deng XueMei yellow (0), a marker for low body weight in Drosophila melanogaster //SCIENCE IN CHINA SERIES C-LIFE SCIENCES Volume: 52 Issue: 7 Pages: 672-682 JUL 2009

Marker-assisted selection (MAS) is an important modern breeding technique, but it has been found that the effect of the markers for quantitative trait loci (QTL) is inconsistent, leading in some cases to MAS failure and raising doubts about its effectiveness. Here the model organism Drosophila melanogaster was employed to study whether an effective marker could be found and applied to MAS. We crossed the stock carrying the y (0) marker (a recessive mutation allele of the yellow gene on the X chromosome) with three other stocks carrying corresponding wild-type markers in an F2 design, and found that the y (0) marker was in significant association with low body weight (P < 0.001). This association was consistent across different backgrounds and the marker effects in female and male were approximately 0.95 sigma (P) (phenotypic standard deviation) and 0.68 sigma (P), respectively. We next introgressed a fragment via the y (0) marker into a wild stock background over 20 generations of marker-assisted introgression (MAI), and constructed the introgression stock y (0)(OR)20 in which body weight decreased by 13% and 7%, in female and male, respectively, compared to the wild stock (P < 0.0001). This indicated that there must be a single QTL for low body weight that is tightly linked to the y (0) marker. We then shortened the introgressed fragment to less than 1.5 cM by a deeper MAI using the y (0) marker and the white marker. This narrower fragment also resulted in a similar decrease in body weight to that induced by y (0)(OR)20, indicating that the QTL for low body weight is located within this less-than-1.5 cM interval. Molecular characteristics of the y (0) marker by PCR amplification and Southern blotting revealed that yellow gene was deficient in the y (0) stock, leading to disappearance of melanin from the cuticle and probably influencing the developmental process. The above results confirmed the existence of effective QTL markers applicable to MAS breeding schemes, and their potential application in breeding new stocks.

Li, Xianchun; Bai, Sufen; Cass, Bodil N. Accord insertion in the 5 ' flanking region of CYP6G1 confers nicotine resistance in Drosophila melanogaster //GENE Volume: 502 Issue: 1 Pages: 1-8 JUL 1 2012

What has driven the sweep of the Accord retrotransposon insertion allele of CYP6G1 in the natural populations of Drosophila melanogaster is unknown. Previous studies on the DDT selection hypothesis produced conflicting data. To reexamine the DDT selection hypothesis and search for alternative explanations, we conducted a series of correlation and genetic linkage experiments with eight D. melanogaster natural populations collected from California (CM1, CM2, CM3, and CM7) and Africa (AM2, AM3, AM4, AM7). Diagnostic PCR showed that CM1, CM2, CM7, and AM3 have the Accord insertion in the CYP6G1 locus, whereas the other four strains do not. RT-PCR analysis exhibits a 100% correlation between Accord insertion and CYP6G1 overexpression. However, among the four strains with Accord-mediated CYP6G1 overexpression only CM1 and CM7 are resistant to DDT, and the other two strains (CM2 and AM3), like the four Accord-free strains, are susceptible to DDT. By contrast, all the four strains with Accord-mediated CYP6G1 overexpression are resistant to nicotine, a plant allelochemical. Genetic crosses between DDT resistant and susceptible Accord-insertion strains, as well as crosses between Accord-insertion and Accord-free strains demonstrated that Accord insertion and CYP6G1 overexpression are genetically linked to nicotine resistance rather than DDT resistance. These results suggest that naturally-occurring allelochemicals such as nicotine are the initial driving force for the worldwide prevalence of the Accord insertion allele of CYP6G1 in D. melanogaster natural populations.

Liang, Liang; Luo Liqun. The olfactory circuit of the fruit fly Drosophila melanogaster //SCIENCE CHINA-LIFE SCIENCES Volume: 53 Issue: 4 Pages: 472-484 APR 2010

The olfactory circuit of the fruit fly Drosophila melanogaster has emerged in recent years as an excellent paradigm for studying the principles and mechanisms of information processing in neuronal circuits. We discuss here the organizational principles of the olfactory circuit that make it an attractive model for experimental manipulations, the lessons that have been learned, and future challenges.

Long, Tristan A. F.; Pischedda, Alison; Rice, William R. REMATING IN DROSOPHILA MELANOGASTER: ARE INDIRECT BENEFITS CONDITION DEPENDENT? //EVOLUTION Volume: 64 Issue: 9 Pages: 2767-2774 SEP 2010

By measuring the direct and indirect fitness costs and benefits of sexual interactions, the feasibility of alternate explanations for polyandry can be experimentally assessed. This approach becomes more complicated when the relative magnitude of the costs and/or benefits associated with multiple mating (i.e., remating with different males) vary with female condition, as this may influence the strength and direction of sexual selection. Here, using the model organism Drosophila melanogaster, we test whether the indirect benefits that a nonvirgin female gains by remating ("trading-up") are influenced by her condition (body size). We found that remating by small-bodied, low-fecundity females resulted in the production of daughters of relatively higher fecundity, whereas the opposite pattern was observed for large-bodied females. In contrast, remating had no measurable effect on the relative reproductive success of sons from dams of either body size. These results are consistent with a hypothesis based on sexually antagonistic genetic variation. The implications of these results to our understanding of the evolution and consequences of polyandry are discussed.

Low, Wai Yee; Feil, Susanne C.; Ng, Hooi Ling; et al. Recognition and Detoxification of the Insecticide DDT by Drosophila melanogaster Glutathione S-Transferase D1 //JOURNAL OF MOLECULAR BIOLOGY Volume: 399 Issue: 3 Pages: 358-366 JUN 11 2010

GSTD1 is one of several insect glutathione S-transferases capable of metabolizing the insecticide DDT. Here we use crystallography and NMR to elucidate the binding of DDT and glutathione to GSTD1. The crystal structure of Drosophila melanogaster GSTD1 has been determined to 1.1 angstrom resolution, which reveals that the enzyme adopts the canonical GST fold but with a partially occluded active site caused by the packing of a C-terminal helix against one wall of the binding site for substrates. This helix would need to unwind or be displaced to enable catalysis. When the C-terminal helix is removed from the model of the crystal structure, DDT can be computationally docked into the active site in an orientation favoring catalysis. Two-dimensional (1)H,(15)N heteronuclear single-quantum coherence NMR experiments of GSTD1 indicate that conformational changes occur upon glutathione and DDT binding and the residues that broaden upon DDT binding support the predicted binding site. We also show that the ancestral GSTD1 is likely to have possessed DDT dehydrochlorinase activity because both GSTD1 from D. melanogaster and its sibling species, Drosophila simulans, have this activity.

Lozinsky, Oleksandr V.; Lushchak, Oleh V.; Kryshchuk, Natalia I.; et al. S-nitrosoglutathione-induced toxicity in Drosophila melanogaster: Delayed pupation and induced mild oxidative/nitrosative stress in eclosed flies //COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY Volume: 164 Issue: 1 Pages: 162-170 JAN 2013

The toxicity of the nitric oxide donor S-nitrosoglutathione (GSNO) was tested on the Drosophila melanogaster model system. Fly larvae were raised on food supplemented with GSNO at concentrations of 1.0, 1.5 or 4.0 mM. Food supplementation with GSNO caused a developmental delay in the flies. Biochemical analyses of oxidative stress markers and activities of antioxidant and associated enzymes were carried out on 2-day-old flies that emerged from control larvae and larvae fed on food supplemented with GSNO. Larval exposure to GSNO resulted in lower activities of aconitase in both sexes and also lower activities of catalase and isocitrate dehydrogenase in adult males relative to the control cohort. Larval treatment with GSNO resulted in higher carbonyl protein content and higher activities of glucose-6-phosphate dehydrogenase in males and higher activities of superoxide dismutase and glutathione-S-transferase in both sexes. Among the parameters tested, aconitase activity and developmental end points may be useful early indicators of toxicity caused by GSNO.

Mamolen, Megan; Andrulis, Erik D. Characterization of the Drosophila melanogaster Dis3 ribonuclease //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 390 Issue: 3 Pages: 529-534 DEC 18 2009

The Dis3 ribonuclease is a member of the hydrolytic RNR protein family. Although much progress has been made in understanding the structure, function, and enzymatic activities of prokaryotic RNR family members RNase 11 and RNase R, there are no activity studies of the metazoan ortholog, Dis3. Here, we characterize the activity of the Drosophila melanogaster Dis3 (dDis3) protein. We find that dDis3 is active in the presence of various monovalent and divalent cations, and requires divalent cations for activity. dDis3 hydrolyzes compositionally distinct RNA substrates, yet releases different products depending upon the substrate. Additionally, dDis3 remains active when lacking N-terminal domains, suggesting that an independent active site resides in the C-terminus of the protein. Finally, a study of dDis3 interactions with dRrp6 and core exosome subunits in extracts revealed sensitivity to higher divalent cation concentrations and detergent, suggesting the presence of both ionic and hydrophobic interactions in dDis3-exosome complexes. Our study thus broadens our mechanistic understanding of the general ribonuclease activity of Dis3 and RNR family members.

Marvin, Katherine A.; Reinking, Jeffrey L.; Lee, Andrea J.; et al. Nuclear Receptors Homo sapiens Rev-erb beta and Drosophila melanogaster E75 Are Thiolate-Ligated Heme Proteins Which Undergo Redox-Mediated Ligand Switching and Bind CO and NO //BIOCHEMISTRY Volume: 48 Issue: 29 Pages: 7056-7071 JUL 28 2009

Nuclear receptors E75, which regulates development in Drosophila melanogaster, and Rev-erb beta, which regulates circadian rhythm in humans, bind heme within their ligand binding, domains (LBD). The heme-bound ligand binding domains of E75 and Rev-erb beta Were studied using electronic absorption, MCD, resonance Raman, and EPR spectroscopies. Both proteins undergo redox-dependent ligand switching and CO- and NO-induced ligand displacement. In the Fe(I 11) oxidation state, the nuclear receptor hemes are low spin and 6-coordinate with cysteine(thiolate) as one of the two axial heme ligands. The sixth ligand is a neutral donor, presumably histidine. When the heme is reduced to the Fe(l 1) oxidation state, the cysteine(thiolate) is replaced by a different neutral donor ligand, whose identity is not known, CO binds to the Fe(II) heme in both E75(LBD) and Rev-erb beta(LBD) opposite a sixth neutral ligand, plausibly the same histidine that served as the sixth ligand in the Fe(III) state. NO binds to the heme of both proteins; however, the NO-heme is 5-coordinate in E75 and 6-coordinate in Rev-erb beta. These nuclear receptors exhibit coordination characteristics that are similar to other known redox and Gas sensors, suggesting that E75 and Rev-erb beta may function in heme-, redox-, or gas-regulated control of cellular function.

McEachern, Lori A.; Lloyd, Vett K. The maize b1 paramutation control region causes epigenetic silencing in Drosophila melanogaster //MOLECULAR GENETICS AND GENOMICS Volume: 287 Issue: 7 Pages: 591-606 JUL 2012

Paramutation is an epigenetic process in which a combination of alleles in a heterozygous organism results in a meiotically stable change in expression of one of the alleles. The mechanisms underlying paramutation are being actively investigated, and examples have been described in both plants and mammals, suggesting that it may utilize epigenetic mechanisms that are widespread and evolutionarily conserved. Paramutation at the well-studied maize b1 locus requires a control region consisting of seven 853 bp tandem repeats. To study the conservation of the epigenetic mechanisms underlying seemingly unique epigenetic processes such as paramutation, we created transgenic Drosophila melanogaster carrying the maize b1 control region adjacent to the Drosophila white reporter gene. We show that the b1 tandem repeats cause silencing of the white reporter in Drosophila. A single copy of the tandem repeat sequence is sufficient to cause silencing, and silencing strength increases as the number of tandem repeats increases. Additionally, transgenic lines with the full seven tandem repeats demonstrate evidence of either pairing-sensitive silencing and silencing in trans, or epigenetic activation in trans. These trans-interactions are dependent on repeat number, similar to maize b1 paramutation. Also, as in maize, the tandem repeats are bidirectionally transcribed in Drosophila. These results indicate that the maize b1 tandem repeats function as an epigenetic silencer and mediate trans-interactions in Drosophila, and support the hypothesis that the mechanisms underlying such epigenetic processes are conserved.

Moehle, Kerstin; Freund, Annabelle; Kubli, Eric; et al. NMR studies of the solution conformation of the sex peptide from Drosophila melanogaster //FEBS LETTERS Volume: 585 Issue: 8 Pages: 1197-1202 APR 20 2011

The insect sex peptide (SP) elicits a variety of biological responses upon transfer to the mated female. SP contains 36 amino acids, including a tryptophan-rich N-terminal region, a central region containing five hydroxyproline (Hyp) residues, and a C-terminal region enclosed by a disulfide bridge. The solution structure of SP, studied here using NMR spectroscopy, includes a motif WPWN that adopts a type I beta-turn in the N-terminal Trp-rich region. This turn region is connected to the central Hyp-rich region, which adopts extended and/or PPII-like conformations. The C-terminal disulfide-bonded loop populates helical turns or nascent helical structure. Overall, the results reveal a rather flexible peptide that lacks a compact folded structure in solution.

Moloney, Aileen; Sattelle, David B.; Lomas, David A.; et al. Alzheimer's disease: insights from Drosophila melanogaster models //TRENDS IN BIOCHEMICAL SCIENCES Volume: 35 Issue: 4 Pages: 228-235 APR 2010

The power of fruit fly genetics is being deployed against some of the most intractable and economically significant problems in modern medicine, the neurodegenerative diseases. Fly models of Alzheimer's disease can be exposed to the rich diversity of biological techniques that are available to the community and are providing new insights into disease mechanisms, and assisting in the identification of novel targets for therapy. Similar approaches might also help us to interpret the results of genome-wide association studies of human neurodegenerative diseases by allowing us to triage gene "hits" according to whether a candidate risk factor gene has a modifying effect on the disease phenotypes in fly model systems.

Muha, Villo; Zagyva, Imre; Venkei, Zsolt; et al. Nuclear localization signal-dependent and -independent movements of Drosophila melanogaster dUTPase isoforms during nuclear cleavage //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 381 Issue: 2 Pages: 271-275 APR 3 2009

Two dUTPase isoforms (23 kDa and 21 kDa) are present in the fruitfly with the sole difference of an N-terminal extension. In Drosophila embryo, both isoforms are detected inside the nucleus. Here, we investigated the function of the N-terminal segment using eYFP-dUTPase constructs. In Schneider 2 cells, only the 23 kDa construct showed nuclear localization arguing that it may contain a nuclear localization signal (NLS). Sequence comparisons identified a lysine-rich nonapeptide with similarity to the human c-myc NLS. In Drosophila embryos during nuclear cleavages, the 23 kDa isoform showed the expected localization shifts. Contrariwise, although the 21 kDa isoform was excluded from the nuclei during interphase, it was shifted to the nucleus during prophase and forthcoming mitotic steps. The observed dynamic localization character showed strict timing to the nuclear cleavage phases and explained how both isoforms can be present within the nuclear microenvironment, although at different stages of cell cycle

Nakayama, Minoru; Yamaguchi, Shin-ichiroh; Sagisu, Yoshiko; et al. Loss of RecQ5 leads to spontaneous mitotic defects and chromosomal aberrations in Drosophila melanogaster //DNA REPAIR Volume: 8 Issue: 2 Pages: 232-241 FEB 1 2009

RecQ5 belongs to the RecQ DNA helicase family that includes genes causative of Bloom, Werner, and Rothmund-Thomson syndromes. Although no human disease has been genetically linked to a mutation in RecQ5. Drosophila melanogaster RecQ5 is highly expressed in early embryos, suggesting an important role for it in the DNA metabolism of the early embryo. In this present study, we generated RecQ5 mutants in D. melanogaster. Embryos lacking maternally derived RecQ5 contained irregular nuclei in early embryogenesis. These irregular nuclei emerged in nuclear cycle 11-13, lost cell-cycle markers, and were located below the surface monolayer of nuclei. By time-lapse microscopy, these irregular nuclei were observed not to divide. whereas all neighboring nuclei proceeded through normal mitotic division with synchrony. These data suggest that the irregular nuclei exited from the nuclear division cycle. This phenotype is reminiscent of the effect of X-ray irradiation on wild-type embryos and was rescued by expression of RecQ5. Thus, the maternal supply of RecQ5 is important for the nuclear cycles in syncytical embryos. Furthermore. the frequencies of spontaneous and induced chromosomal aberrations were increased in RecQ5 mutant neuroblasts. These data imply that DNA damage accumulates spontaneously in RecQ5 mutants. Therefore, endogenous genomic damage may be produced in Drosophila development, and RecQ5 would be involved in the maintenance of genomic stability by suppressing the accumulation of DNA damage.

Namiki, Toshiki; Niwa, Ryusuke; Higuchi, Atsushi; et al. A Basic-HLH Transcription Factor, HLH54F, Is Highly Expressed in the Prothoracic Gland in the Silkworm Bombyx mori and the Fruit Fly Drosophila melanogaster //BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY Volume: 73 Issue: 3 Pages: 762-765 MAR 2009

We describe our findings on HLH54F, a basic helix-loop-helix transcription factor gene that was highly expressed in the prothoracic gland, an organ producing the insect steroid ecdysone. HLH54F was uncovered by the use of an expressed sequence tag database of the silkworm Bombyx mori. It was also highly expressed in the prothoracic gland of the fruit fly Drosophila melanogaster.

Nichols, Andrew S.; Luetje, Charles W. Transmembrane Segment 3 of Drosophila melanogaster Odorant Receptor Subunit 85b Contributes to Ligand-Receptor Interactions //JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 285 Issue: 16 Pages: 11854-11862 APR 16 2010

The OR class insect odorant receptors are ligand-gated ion channels comprised of at least one common subunit (OR83b in Drosophila) and at least one putative odorant-binding subunit. However, little else is known about the molecular details of insect OR architecture. For example, nothing is known about how these receptors bind odorants, greatly limiting efforts to develop insect OR-targeted compounds for the control of insects involved in disease propagation and agricultural damage. Here we identify a portion of a Drosophila OR that is involved in odorant activation of the receptor. Using the substituted cysteine accessibility method, we identified residues 146150 of OR85b, located at the predicted interface between transmembrane segment 3 (TMS3) and extracellular loop 2 (ECL2), as playing a role in odorant (2-heptanone) activation. We found that occupation of the receptor by the competitive antagonist 2-nonanone protected the receptor from methanethiosulfonate action at position 148, placing this region close to the odorant-binding site. In addition, mutations at positions 142 and 143 within TMS3 altered odorant sensitivity. Our results identify the involvement of the extracellular half of TMS3 in Drosophila OR85b in odorant activation of the receptor. This finding can serve as a starting point for future detailed analysis of the molecular basis for odorant recognition by insect ORs, a novel class of ligand-gated channel.

Ogura, Keiji; Magae, Junji; Kawakami, Yasushi; et al. Reduction in Mutation Frequency by Very Low-Dose Gamma Irradiation of Drosophila melanogaster Germ Cells //RADIATION RESEARCH Volume: 171 Issue: 1 Pages: 1-8 JAN 2009

To determine whether the linear no-threshold (LNT) model for stochastic effects of ionizing radiation is applicable to very low-dose radiation at a low dose rate, we irradiated immature male germ cells of the fruit fly, Drosophila melanogaster, with several doses of (60)Co gamma rays at a dose rate of 22.4 mGy/h. Thereafter, we performed the sex-linked recessive lethal mutation assay by mating the irradiated males with nonirradiated females. The mutation frequency in the group irradiated with 500 mu Gy was found to be significantly lower than that in the control group (P < 0.01), whereas in the group subjected to 10 Gy irradiation, the mutation frequency was significantly higher than that in the control group (P < 0.03). A J-shaped dose-response relationship was evident. Molecular experiments using DNA microarray and quantitative reverse transcription PCR indicated that several genes known to be expressed in response to heat or chemical stress and grim, a positive regulator of apoptosis, were up-regulated immediately after irradiation with 500 mu Gy. The involvement of an apoptosis function in the non-linear dose-response relationship was suggested

Ohsako, Takashi; Yamamoto, Masa-Toshi Sperm of the wasted mutant are wasted when females utilize the stored sperm in Drosophila melanogaster //GENES & GENETIC SYSTEMS Volume: 86 Issue: 2 Pages: 97-108 APR 2011

Females of many animal species store sperm after copulation for use in fertilization, but the mechanisms controlling sperm storage and utilization are largely unknown. Here we describe a novel male sterile mutation of Drosophila melanogaster, wasted (wst), which shows defects in various processes of sperm utilization. The sperm of wst mutant males are stored like those of wild-type males in the female sperm storage organs, the spermathecae and seminal receptacles, after copulation and are released at each ovulation. However, an average of thirteen times more wst sperm than wild type sperm are released at each ovulation, resulting in rapid loss of sperm stored in seminal receptacles within a few days after copulation. wst sperm can enter eggs efficiently at 5 hr after copulation, but the efficiency of sperm entry decreases significantly by 24 hr after copulation, suggesting that wst sperm lose their ability to enter eggs during storage. Furthermore, wst sperm fail to undergo nuclear decondensation, which prevents the process of fertilization even when sperm enter eggs. Our results indicate that the wst gene is essential for independent processes in the utilization of stored sperm; namely, regulation of sperm release from female storage organs, maintenance of sperm efficiency for entry into eggs, and formation of the male pronucleus in the egg at fertilization.

Olenkina, Oxana M.; Egorova, Ksenia S.; Kibanov, Mikhail V.; et al. Promoter contribution to the testis-specific expression of Stellate gene family in Drosophila melanogaster //GENE Volume: 499 Issue: 1 Pages: 143-153 MAY 10 2012

Testis-specific tandemly repeated Stellate genes are part of the Ste-Su(Ste) genetic system required for male fertility in Drosophila melanogaster. Stellate genes encode a functional homolog of the beta-subunit of protein kinase CK2. Derepression of Stellate results in their over-expression, meiotic disturbances and male sterility. Stellate genes are represented by clustered copies in the X chromosome and carry promoters shared with another X-chromosome cluster, beta NACtes genes, encoding putative beta-subunits of the nascent polypeptide-associated complex. Using Electrophoretic Mobility Shift Assay, we revealed in the Stellate promoter three cis-acting elements, E-boxes, the loss of which greatly diminished the reporter gene expression in Drosophila testes. We identified that these E-boxes were recognized by helix-loop-helix protein, dUSF (Drosophila ortholog of mammalian USF) in testis nuclear extract. All three E-boxes were preserved in the promoters of both euchromatic and heterochromatic Stellate clusters. Two analogous E-boxes were detected in the promoters of 5'-copies of the duplicated beta NACtes gene pairs, whereas the 3'-copies lacked these sites but possessed a new binding site for a testis protein distinct from dUSF. Here we characterized a new type of testis-specific core promoter and identified dUSF as its interacting transcription factor.

Ono, Hajime; Morita, Sayo; Asakura, Ichiyoh; et al. Conversion of 3-oxo steroids into ecdysteroids triggers molting and expression of 20E-inducible genes in Drosophila melanogaster //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 421 Issue: 3 Pages: 561-566 MAY 11 2012

Parkash, Ravi; Aggarwal, Dau Dayal Trade-off of energy metabolites as well as body color phenotypes for starvation and desiccation resistance in montane populations of Drosophila melanogaster //COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY Volume: 161 Issue: 2 Pages: 102-113 FEB 2012

Storage of energy metabolites has been investigated in different sets of laboratory selected desiccation or starvation resistant lines but few studies have examined such changes in wild-caught populations of Drosophila melanogaster. In contrast to parallel selection of desiccation and starvation tolerance under laboratory selection experiments, opposite dines were observed in wild populations of D. melanogaster. If resistance to desiccation and starvation occurs in opposite directions under field conditions, we may expect a trade-off for energy metabolites but such correlated changes are largely unknown. We tested whether there is a trade-off for storage as well as actual utilization of carbohydrates (trehalose and glycogen), lipids and proteins in D. melanogaster populations collected from different altitudes (512-2500 m). For desiccation resistance, darker flies (>50% body melanization) store more body water content and endure greater loss of water (higher dehydration tolerance) as compared to lighter flies (<30% body melanization). Based on within population analysis, we found evidence for coadapted phenotypes i.e. darker flies store and actually utilize more carbohydrates to confer greater desiccation resistance. In contrast, higher starvation resistance in lighter flies is associated with storage and actual utilization of greater lipid amount. However, darker and lighter flies did not vary in the rate of utilization of carbohydrates

Peschel, Nicolai; Helfrich-Foerster, Charlotte Setting the clock - by nature: Circadian rhythm in the fruitfly Drosophila melanogaster //FEBS LETTERS Volume: 585 Issue: 10 Pages: 1435-1442 MAY 20 2011

Nowadays humans mainly rely on external, unnatural clocks such as of cell phones and alarm clocks - driven by circuit boards and electricity. Nevertheless, our body is under the control of another timer firmly anchored in our genes. This evolutionary very old biological clock drives most of our physiology and behavior. The genes that control our internal clock are conserved among most living beings. One organism that shares this ancient clock mechanism with us humans is the fruitfly Drosophila melanogaster. Since it turned out that Drosophila is an excellent model, it is no surprise that its clock is very well and intensely investigated. In the following review we want to display an overview of the current understanding of Drosophila's circadian clock.

Ren, Jian-Ching; Rebrin, Igor; Klichko, Vladimir; et al. Cytochrome c oxidase loses catalytic activity and structural integrity during the aging process in Drosophila melanogaster //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 401 Issue: 1 Pages: 64-68 OCT 8 2010

The hypothesis, that structural deterioration of cytochrome c oxidase (CcO) is a causal factor in the agerelated decline in mitochondrial respiratory activity and an increase in H(2)O(2) generation, was tested in Drosophila melanogaster. CcO activity and the levels of seven different nuclear DNA-encoded CcO subunits were determined at three different stages of adult life, namely, young-, middle-, and old-age. CcO activity declined progressively with age by 33%. Western blot analysis, using antibodies specific to Drosophila CcO subunits IV, Va, Vb, VIb, VIc, VIIc, and VIII, indicated that the abundance these polypeptides decreased, ranging from 11% to 40%, during aging. These and previous results suggest that CcO is a specific intra-mitochondrial site of age-related deterioration, which may have a broad impact on mitochondrial physiology.

Ryuda, Masasuke; Tsuzuki, Seiji; Matsumoto, Hitoshi; et al. Identification of a Novel Gene, Anorexia, Regulating Feeding Activity via Insulin Signaling in Drosophila melanogaster //JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 286 Issue: 44 Pages: 38417-38426 NOV 4 2011

Feeding activities of animals, including insects, are influenced by various signals from the external environment, internal energy status, and physiological conditions. Full understanding of how such signals are integrated to regulate feeding activities has, however, been hampered by a lack of knowledge about the genes involved. Here, we identified an anorexic Drosophila melanogaster mutant (GS1189) in which the expression of a newly identified gene, Anorexia (Anox), is mutated. In Drosophila larvae, Anox encodes an acyl-CoA binding protein with an ankyrin repeat domain that is expressed in the cephalic chemosensory organs and various neurons in the central nervous system (CNS). Loss of its expression or disturbance of neural transmission in Anox-expressing cells decreased feeding activity. Conversely, overexpression of Anox in the CNS increased food intake. We further found that Anox regulates expression of the insulin receptor gene (dInR); overexpression and knockdown of Anox in the CNS, respectively, elevated and repressed dInR expression, which altered larval feeding activity in parallel with Anox expression levels. Anox mutant adults also showed significant repression of sugar-induced nerve responses and feeding potencies. Although Anox expression levels did not depend on the fasting and feeding states cycle, stressors such as high temperature and desiccation significantly repressed its expression levels. These results strongly suggest that Anox is essential for gustatory sensation and food intake of Drosophila through regulation of the insulin signaling activity that is directly regulated by internal nutrition status. Therefore, the mutant strain lacking Anox expression cannot enhance feeding potencies even under starvation.

Saisawang, Chonticha; Wongsantichon, Jantana; Ketterman, Albert J. A preliminary characterization of the cytosolic glutathione transferase proteome from Drosophila melanogaster //BIOCHEMICAL JOURNAL Volume: 442 Pages: 181-190 Part: 1 Published: FEB 15 2012

The cytosolic GST (glutathione transferase) superfamily has been annotated in the Drosophila melanogaster genome database. Of 36 genes, four undergo alternative splicing to yield a total of 41 GST proteins. In the present study, we have obtained the 41 transcripts encoding proteins by RT (reverse transcription)-PCR using RNA template from Drosophila S2 cells, an embryonic cell line. This observation suggests that all of the annotated DmGSTs (D. melanogaster GSTs) in the proteome are expressed in the late embryonic stages of D. melanogaster. To avoid confusion in naming these numerous DmGSTs, we have designated them following the universal GST nomenclature as well as previous designations that fit within this classification. Furthermore, in the cell line, we identified an apparent processed pseudogene, gste8, in addition to two isoforms from the Delta class that have been published previously. Only approximately one-third of the expressed DmGSTs could be purified by conventional GSH affinity chromatography. The diverse kinetic properties as well as physiological substrate specificity of the DmGSTs are such that each individual enzyme displayed a unique character even compared with members from the same class.

Sawamura, Kyoichi. Genetics of postmating isolation between Drosophila melanogaster and Drosophila simulans //GENES & GENETIC SYSTEMS Volume: 85 Issue: 6 Pages: 452 DEC 2010

Sellami, Azza; Wegener, Christian; Veenstra, Jan A. Functional significance of the copper transporter ATP7 in peptidergic neurons and endocrine cells in Drosophila melanogaster //FEBS LETTERS Volume: 586 Issue: 20 Pages: 3633-3638 OCT 19 2012

The Drosophila ATP7 copper transporter has sequence homology to the human copper transporters A'TP7A and ATP7B, which are defective in Menkes and Wilson disease, respectively. We show here that in Drosophila ATP7 is expressed by many peptidergic neurons. As C-terminal amidation of neuropeptides depends on the copper-containing enzyme PHM, it seemed likely that in the absence of ATP7 the activity of PHM might be compromised. Indeed, inhibition of ATP7 expression by RNAi led to a decrease in mature amidated neuropeptides and the appearance of C-terminally Gly-extended neuropeptides. The strength of this effect differed from one cell type to another, it was very pronounced for AKH and corazonin, but much less so for SIFamide and myosuppressin. Nevertheless, down-regulation of ATP7 specifically in the SIFamide-expressing neurons resulted in male-male courtship behavior.

Shiotani, Shigenobu; Yanai, Nobuya; Suzuki, Takanori; et al. Effect of a Dipeptide-Enriched Diet in an Adult Drosophila melanogaster Laboratory Strain //BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY Volume: 77 Issue: 4 Pages: 836-838 APR 2013

Here we present free amino acid profiles for Drosophila melanogaster adults. Imidazol dipeptides anserine and carnosine, which are abundant in mammalian muscle tissue, are not present in Drosophila. Dipeptide-enriched food altered the amino acid balance, suggesting that the free amino acid content is nutrition-dependent and probably mediated by dipeptides.

Suh, Eunho; Mercer, David R.; Fu, Yuqing; et al. Pathogenicity of Life-Shortening Wolbachia in Aedes albopictus after Transfer from Drosophila melanogaster //APPLIED AND ENVIRONMENTAL MICROBIOLOGY Volume: 75 Issue: 24 Pages: 7783-7788 DEC 15 2009

Maternally inherited Wolbachia bacteria have evolved mechanisms to manipulate the reproduction of their invertebrate hosts, promoting infection spread. A high fitness cost to the host is maladaptive for obligate endosymbionts, and prior studies show rapid selection of new Wolbachia associations toward commensal or mutualistic symbioses. Here, wMelPop Wolbachia is transferred from Drosophila melanogaster into the mosquito Aedes albopictus. Characterization of the resulting strain provides an extreme example of Wolbachia as a pathogen. In addition to reduced longevity and fecundity, abnormally high Wolbachia density is associated with embryonic mortality that masks the typical pattern of cytoplasmic incompatibility. The results are consistent with earlier reports that show unpredictable shifts in the Wolbachia phenotype after interspecific transfer, which can complicate proposed strategies to modify the age structure of medically important vector populations.

Tanco, Sebastian; Arolas, Joan L.; Guevara, Tibisay; et al. Structure-Function Analysis of the Short Splicing Variant Carboxypeptidase Encoded by Drosophila melanogaster silver //JOURNAL OF MOLECULAR BIOLOGY Volume: 401 Issue: 3 Pages: 465-477 AUG 20 2010

Drosophila melanogaster silver gene is the ortholog of the coding gene of mammalian carboxypeptidase D (CPD). The silver gene gives rise to eight different splicing variants of differing length that can contain up to three homologous repeats. Among the protein variants encoded, the short form 1B alias DmCPD1Bs (D. melanogaster CPD variant 1B short) is necessary and sufficient for viability of the fruit fly. It has one single repeat, it is active against standard peptide substrates, and it is localized to the secretory pathway. In this work, the enzyme was found as a monomer in solution and as a homodimer in the crystal structure, which features a protomer with an N-terminal 311-residue catalytic domain of alpha/beta-hydrolase fold and a C-terminal 84-residue all-beta transthyretin-like domain. Overall, DmCPD1Bs conforms to the structure of N/E-type funnelins/M14B metallopeptidases, but it has two unique structural elements potentially involved in regulation of its activity: (i) two contiguous surface cysteines that may become palmitoylated and target the enzyme to membranes, thus providing control through localization, and (ii) a surface hot spot targetable by peptidases that would provide a regulatory mechanism through proteolytic inactivation. Given that the fruit fly possesses orthologs of only two out of the five proteolytically competent N/E-type funnelins found in higher vertebrates, DmCPD1Bs may represent a functional analog of at least one of the missing mammalian CPs.

Thorat, Leena J.; Gaikwad, Sushama M.; Nath, Bimalendu B. Trehalose as an indicator of desiccation stress in Drosophila melanogaster larvae: A potential marker of anhydrobiosis //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 419 Issue: 4 Pages: 638 MAR 23 2012

In the current scenario of global climate change, desiccation is considered as one of the major environmental stressors for the biota exposed to altered levels of ambient temperature and humidity. Drosophila melanogaster, a cosmopolitan terrestrial insect has been chosen as a humidity-sensitive bioindicator model for the present study since its habitat undergoes frequent stochastic and/or seasonally aggravated dehydration regimes. We report here for the first time the occurrence of anhydrobiosis in D. melanogaster larvae by subjecting them to desiccation stress under laboratory conditions. Larvae desiccated for ten hours at <5% relative humidity could enter anhydrobiosis and could revive upon rehydration followed by resumption of active metabolism. As revealed by FIR and HPLC analyzes, our findings strongly indicated the synthesis and accumulation of trehalose in the desiccating larvae. Biochemical measurements pointed out the desiccation-responsive trehalose metabolic pathway that was found to be coordinated in concert with the enzymes trehalose 6-phosphate synthase and trehalase. Further, an inhibitor-based experimental approach using deoxynojirimycin, a specific trehalase inhibitor, demonstrated the pivotal role of trehalose in larval anhydrobiosis of D. melanogaster. We therefore propose trehalose as a potential marker for the assessment of anhydrobiosis in Drosophila. The present findings thus add to the growing list of novel biochemical markers in specific bioindicator organisms for fulfilling the urgent need of environmental biomonitoring of climate change.

Tian, Feng; Chen, Jia; Bao, Suying; et al. A graph model based study on regulatory impacts of transcription factors of Drosophila melanogaster and comparison across species //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 386 Issue: 4 Pages: 559-562 SEP 4 2009

Transcription factor binding sites and the cis-regulatory modules they compose are central determinants of gene regulation. The gene regulations in some model species have been well addressed. However, not as much is known about the fly due to the lack of experimental data. To study the transcription regulation of Drosophila melanogaster genes, we analyzed the regulation data from ChIP chip experiments as well as the regulatory database. A graph-based approach is applied to study the impacts of each transcription factor to the regulatory network. The model is also applied to Saccharomyces cerevisiae and Homo sapiens to study the behaviors of transcription factors in different species. Gene ontology annotations were used for further studies of the biological significance of studied transcription factors.

Tohyama, Daisuke; Yamaguchi, Atsushi A critical role of SNF1A/dAMPK alpha (Drosophila AMP-activated protein kinase alpha) in muscle on longevity and stress resistance in Drosophila melanogaster //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 394 Issue: 1 Pages: 112-118 MAR 26 2010

Energy homeostasis and stress resistance are closely linked on aging and longevity. AMPK (AMP-activated protein kinase) is a sensor of cellular energy status activated by metabolic stress that accelerates AMP/ATP ratio, regulating cell polarity, metabolic homeostasis and sensitivity to stress resistance. AMPK could be therapeutic targets for cancer, diabetic mellitus and obesity, providing a possible link to metabolic syndrome. However, little is known how functional deficiency of AMPK affects longevity and stress resistance in vivo due to its redundancy and lethality in null-mutant. SNF1A/dAMPK alpha (CG3051) is a single orthologue for its mammalian counterparts in Drosophila melanogaster. Using time- and tissue-specific RNAi system in D. melanogaster, we found that adult-onset inhibition of dAMPK alpha especially in muscle shortens lifespan. In addition, inhibition of dAMPK alpha in muscle enhances sensitivity to paraquat and starvation stress. Real-time PCR analysis showed that inhibition of dAMPK alpha in muscle affected the transcriptional regulation of various genes in response to starvation. These results raise the possibility that muscle is one of major tissues in which AMPK plays a critical role on longevity and stress resistance and the intervention to activate AMPK in muscle could be a prominent treatment strategy for longevity.

Tseng, Tien-Sheng; Cheng, Chao-Sheng; Chen, Dian-Jiun; et al. A molten globule-to-ordered structure transition of Drosophila melanogaster crammer is required for its ability to inhibit cathepsin //BIOCHEMICAL JOURNAL Volume: 442 Pages: 563-572 Part: 3 MAR 15 2012

Drosophila melanogaster crammer is a novel cathepsin inhibitor that is involved in LTM (long-term memory) formation. The mechanism by which the inhibitory activity is regulated remains unclear. In the present paper we have shown that the oligomeric state of crammer is pH dependent. At neutral pH, crammer is predominantly dimeric in vitro as a result of disulfide bond formation, and is monomeric at acidic pH. Our inhibition assay shows that monomeric crammer, not disulfide-bonded dimer, is a strong competitive inhibitor of cathepsin L. Crammer is a monomeric molten globule in acidic solution, a condition that is similar to the environment in the lysosome where crammer is probably located. Upon binding to cathepsin L, however, crammer undergoes a molten globule-to-ordered structural transition. Using high-resolution NMR spectroscopy, we have shown that a cysteine-to-serine point mutation at position 72 (C72S) renders crammer monomeric at pH 6.0 and that the structure of the C72S variant highly resembles that of wild-type crammer in complex with cathepsin L at pH 4.0. We have determined the first solution structure of propeptide-like protease inhibitor in its active form and examined in detail using a variety of spectroscopic methods the folding properties of crammer in order to delineate its biomolecular recognition of cathepsin.


Body size and thermal tolerance clines in Drosophila melanogaster occur along the east coast of Australia. However the extent to which temperature affects the genetic architecture underlying the observed clinal divergence remains unknown. Clinal variation in these traits is associated with cosmopolitan chromosome inversions that cline in D. melanogaster. Whether this association influences the genetic architecture for these traits in D. melanogaster is unclear. Drosophila simulans shows linear clines in body size, but nonlinear clines in cold resistance. Clinally varying inversions are absent in D. simulans. Line-cross and clinal analyses were performed between tropical and temperate populations of D. melanogaster and D. simulans from the east coast of Australia to investigate whether clinal patterns and genetic effects contributing to clinal divergence in wing centroid size, thorax length, wing-to-thorax ratio, cold and heat resistance differed under different developmental temperatures (18 degrees C, 25 degrees C, and 29 degrees C). Developmental temperature influenced the genetic architecture in both species. Similarities between D. melanogaster and D. simulans suggest clinally varying inversion polymorphisms have little influence on the genetic architecture underlying clinal divergence in size in D. melanogaster. Differing genetic architectures across different temperatures highlight the need to consider different environments in future evolutionary and molecular studies of phenotypic divergence.

Vognsen, Tina; Kristensen, Ole Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster // BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 420 Issue: 1 Pages: 188-192 MAR 30 2012

The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7 angstrom resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a beta-sheet and three alpha-helices forming a cone-like shape. However, known binding sites for RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site.


Sexually dimorphic traits are by definition exaggerated in one sex, which may arise from a history of sex-specific selection-in males, females, or both. If this exaggeration comes at a cost, exaggeration is expected to be greater in higher condition individuals (condition-dependent). Although studies using small numbers of morphological traits are generally supportive, this prediction has not been examined at a larger scale. We test this prediction across the transcriptome by determining the condition-dependence of sex-biased (dimorphic) gene expression. We find that high-condition populations are more sexually dimorphic in transcription than low-condition populations. High-condition populations have more male-biased genes and more female-biased genes, and a greater degree of sexually dimorphic expression in these genes. Also, condition-dependence in male-biased genes was greater than in a set of unbiased genes. Interestingly, male-biased genes expressed in the testes were not more condition-dependent than those in the soma. By contrast, increased female-biased expression under high condition may have occurred because of the greater contribution of the ovary-specific transcripts to the entire mRNA pool. We did not find any genomic signatures distinguishing the condition-dependent sex-biased genes. The degree of condition-dependent sexual dimorphism (CDSD) did not differ between the autosomes and the X chromosome. There was only weak evidence that rates of evolution correlated with CDSD. We suggest that the sensitivity of both female-biased genes and male-biased genes to condition may be akin to the overall heightened sensitivity to condition that life-history and sexually selected traits tend to exhibit. Our results demonstrate that through condition-dependence, early life experience has dramatic effects on sexual dimorphism in the adult transcriptome.

Xiong, Huiping; Qian, Jinjun; He, Tao; et al. Independent transcription of miR-281 in the intron of ODA in Drosophila melanogaster //BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 378 Issue: 4 Pages: 883-889 JAN 23 2009

MicroRNAs (miRNAs) have recently received much interest for their role in post-transcriptional regulation. However, the study of miRNA transcription lags behind that of gene cloning and functional analysis. The MiR-281 in Drosophila melanogaster is located in the first intron of isoform RA of the ornithine decarboxylase antizyme (ODA) gene. ODA has three isoforms because of alternative transcription start sites (TSSs). Expression profile analysis indicated that miR-281 is not co-expressed with any ODA isoform. We amplified the primary transcripts of miR-281 using the RACE technique. The pri-miRNA is 2149 by with a poly (A) tail and a canonical polyadenylation signal (AATAAA). Chromatin immunoprecipitation analysis confirmed the binding of hypophosphorylated Pol-II and the transcription factor Myc at the core miR-281 promoter region. The abundance of miR-281 does not correlate, either positively or negatively, with the expression of any ODA isoform, indicating that ODA has little influence on the transcription of miR-281.

Yasuno, Yusaku; Kawano, Jun-ichi; Yamamoto, Masa-toshi Electron microscopic observation of the Golgi apparatus during spermatogenesis of Drosophila melanogaster //GENES & GENETIC SYSTEMS Volume: 86 Issue: 6 Pages: 415-415 DEC 2011

Zhao, Huiwen W.; Zhou, Dan; Haddad, Gabriel G. Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster //JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 286 Issue: 8 Pages: 6211-6218 FEB 25 2011

It is well appreciated that reactive oxygen species (ROS) are deleterious to mammals, including humans, especially when generated in abnormally large quantities from cellular metabolism. Whereas the mechanisms leading to the production of ROS are rather well delineated, the mechanisms underlying tissue susceptibility or tolerance to oxidant stress remain elusive. Through an experimental selection over many generations, we have previously generated Drosophila melanogaster flies that tolerate tremendous oxidant stress and have shown that the family of antimicrobial peptides (AMPs) is over-represented in these tolerant flies. Furthermore, we have also demonstrated that overexpression of even one AMP at a time (e. g. Diptericin) allows wild-type flies to survive much better in hyperoxia. In this study, we used a number of experimental approaches to investigate the potential mechanisms underlying hyperoxia tolerance in flies with AMP overexpression. We demonstrate that flies with Diptericin overexpression resist oxidative stress by increasing antioxidant enzyme activities and preventing an increase in ROS levels after hyperoxia. Depleting the GSH pool using buthionine sulfoximine limits fly survival, thus confirming that enhanced survival observed in these flies is related to improved redox homeostasis. We conclude that 1) AMPs play an important role in tolerance to oxidant stress, 2) overexpression of Diptericin changes the cellular redox balance between oxidant and antioxidant, and 3) this change in redox balance plays an important role in survival in hyperoxia.

Александров И.Д., Александрова М.В., Иванов В.В., Степаненко В.В. КОМПЬЮТЕРНЫЕ ПОДХОДЫ К 2- И 3-МЕРНОМУ МОДЕЛИРОВАНИЮ МАКРО-АРХИТЕКТУРЫ ИНТЕРФАЗНЫХ ХРОМОСОМ В ГЕНОМЕ СПЕРМИЕВ DROSOPHILA MELANOGASTER//Вестник Российского университета дружбы народов. Серия: Математика, информатика, физика. 2010. № 3-2. С. 37-40.

Впервые за 125-летнюю историю научных идей о пространственной организации интерфазных хромосом в ядре клеток высших эукариотов представлена экспериментально обоснованная 2- и 3-мерная компьютерная модель макроархитектуры гаплоидных хромосом в геноме спермиев D.melanogster, компактно уложенных в виде мегарозеточно-петлевых образований, на что указывает неслучайное распределение индуцированных гамма-лучами и нейтронами инверсионных и транслокационных точек разрывов по длине хромосом с их кластеризацией вокруг гетерохроматинового комплекса внутри ядра.


Soon after eclosion, epithelial cells of the Drosophila wing undergo a number of the processes due to a release of the neurohormone bursicon and its further binding to the GPCR Rickets, collectively referred to as wing maturation. Here we propose hypothetical models of the interaction between extracellular Miniature, and also Dusky, proteins and proteins responsible for triggering of the wing maturation processes in Drosophila melanogaster.


Исследовано влияние повсеместного подавления экспрессии гена инсулинового рецептора (InR) на метаболизм ювенильного гормона (ЮГ) и дофамина (ДА) у молодых самок D. melanogaster в нормальных условиях и при тепловом стрессе. В качестве индикаторов для оценки уровней ЮГ и ДА использовали уровень деградации ЮГ и активность щелочной фосфатазы (ЩФ – фермента, регулирующего синтез ДА) соответственно. Показано, что повсеместное подавление экспрессии гена InR вызывает у самок D. melanogaster в нормальных условиях повышение уровня деградации ЮГ и активности ЩФ, что свидетельствует, как показано нами ранее, о снижении уровней обоих гормонов. Обнаружено, что повсеместная инактивация InR не влияет на инициацию ответа систем метаболизма ЮГ и ДА на тепловой стресс, но изменяет его интенсивность. Таким образом, in vivo показано участие инсулинового сигнального пути в регуляции метаболизма ЮГ и ДА у самок дрозофилы в нормальных и стрессирующих условиях.

Бурлаков А.Б., Бурцев А.С., Чернова Г.В., Капранов Ю.С., Куфаль Г.Э., Матюхин И.В., Перминов С.В., Першин И.М. МОДИФИКАЦИЯ ПОСТЭМБРИОНАЛЬНОГО РАЗВИТИЯ DROSOPHILA MELANOGASTER С ПОМОЩЬЮ РЕТРОРЕФЛЕКТОРНЫХ ОПТИЧЕСКИХ СИСТЕМ//Электромагнитные волны и электронные системы. 2011. Т. 16. № 11. С. 24-33.

Выявлены на уровне нескольких морфологических и популяционных признаков эффекты прямых дистантных взаимовлияний разновозрастных особей Drosophila melanogaster; показана возможность изменения параметров постэмбрионального развития разновозрастных групп Dr. melanogaster с помощью лазерного уголкового световозвращателя (УСВ); описаны аномалии развития, специфические для определенных сочетаний разновозрастных групп дрозофил при оптическом взаимодействии; предложена модель, показывающая механизм возникновения аномалий развития дрозофил при дистантном взаимодействии разновозрастных групп через УСВ.


Большие щетинки (макрохеты) располагаются упорядоченным образом на голове и теле дрозофилы и образуют характерный для каждого вида щетиночный узор. Простая организация каждого щетиночного органа, который состоит всего из четырех специализированных клеток, делает макрохеты удобной моделью для исследования закономерностей формирования пространственных структур с фиксированным числом элементов и механизма клеточной дифференцировки. В работе систематизированы экспериментальные данные об основных генах и их продуктах, контролирующих три этапа формирования щетиночного узора. На основе созданной базы данных реконструированы две генные сети - «Neurogenesis(determination)» и «Neurogenesis(asymmetric division)». Рассмотрены ключевые элементы и механизмы, обеспечивающие функционирование этих генных сетей.


Популяции человека полиморфны по мутациям ряда генов, предрасполагающих к болезням, в том числе онкологическим. Моделью для изучения этого феномена может служить эволюционно консервативный ген-онкосупрессор lethal (2) giant larvae (lgl), нулевые варианты которого были обнаружены нами повсеместно в природных популяциях дрозофил. Изучали влияние инсерционных и делеционных мутантных аллелей гена lgl на выживаемость и долголетие их носителей в зависимости от генотипа, направления скрещивания, постоянного или импульсного температурного стресс-воздействия. У делеционных гетерозигот lgl/+ при постоянном действии температурного стресса повышалась выживаемость и продолжительность жизни по сравнению с контрольными особями, несущими две нормальных дозы гена. Этот гаплоэффект проявлялся лишь в случае материнского носительства делеционного аллеля. У делеционных гетерозигот импульсное умеренное стресс-воздействие на предзиготические стадии оогенеза сходно влияло на выживаемость потомков. Импульсное действие прогревания на стадии проэмбрио было двунаправленным: позитивным при прогревании зрелых яйцеклеток и негативным в период их дифференцировки. Однако в обоих случаях делетирование одного аллеля онкосупрессора у самок lgl/+ повышало выживаемость следующего поколения, замедляя старение. Эти данные сопоставлены со сходными эпигенетическими трансгенерационными эффектами, найденными ранее у человека.

Васильева Л.А., Антоненко О.В., Захаров И.К. РОЛЬ МОБИЛЬНЫХ ГЕНЕТИЧЕСКИХ ЭЛЕМЕНТОВ В ГЕНОМЕ DROSOPHILA MELANOGASTER//Вавиловский журнал генетики и селекции. 2011. Т. 15. № 2. С. 225-260.

Открытие мобильных генетических элементов (МГЭ) породило проблему выяснения их роли в геномах генетических объектов. Накопившиеся за три последних десятилетия экспериментальные данные позволяют сделать ряд выводов, касающихся поведения и роли МГЭ в геномах. Так, в настоящее время известно, что спонтанная скорость инсерций транспозиций мобильных генетических элементов у дрозофилы в целом на 1-2 порядка величин выше спонтанной скорости возникновения рецессивных мутаций и составляет 10^-10-5 событий на сайт на геном за поколение. Считается, что большинство олигогенных (майор-генных) мутаций - результат инсерций МГЭ. Кроме того, МГЭ могут изменять функцию и активность мажорных и минорных генов, так как в своей структуре содержат мотивы систем управления и энхансеры, состоящие из нескольких модулей и поэтому способные связываться с различными регуляторными белками, активирующими процесс транскрипции. В результате кроссинговера между LTR (длинные концевые повторы) могут возникать хромосомные перестройки различных типов: делеции, дупликации, инверсии. МГЭ могут достраивать теломерные концы хромосом, участвовать в горизонтальном переносе генов. МГЭ откликаются вспышкой транспозиций при различных стрессовых воздействиях на геномы. В работе представлены данные по оценке скоростей индукции транспозиций при внешних стрессовых воздействиях, таких, как холодовой и тепловой шок, пары этанола, у-облучение. Показано, что внешние стрессовые воздействия увеличивают скорость индукции транспозиций МГЭ на 1-2 порядка величин по сравнению со спонтанной скоростью и составляют 10-2-10-3 на сайт на геном за поколение. Кроме того, в результате действия таких генетических факторов, как аутбридинг, инбридинг и селекция, также происходит существенное изменение паттерна мобильных генетических элементов в геноме. Таким образом, можно заключить, что система мобильных генетических элементов в геномах столь же реальна и универсальна, как система SOS-репарации и система гормонального контроля. Можно предположить, что МГЭ выполняют функцию своего рода рецепторов стрессирующих сигналов, инициирующих вспышки транспозиционной изменчивости в критические периоды эволюции популяций. Это может приводить к быстрому преобразованию гомеостатической видовой нормы и, возможно, к видообразованию. Можно предположить, что наличие МГЭ, в частности в геномах эукариот, дает возможность популяциям в целом выживать в резко измененных условиях среды. Следовательно, можно считать, что МГЭ непосредственно участвуют в экспрессии генов, контролирующих признаки, в селекции и эволюции.

Воронцова Ю.Е., Черезов Р.О., Зацепина О.Г., Слезингер М.С., Кузин Б.А., Симонова О.Б. МОДУЛЯЦИЯ ЭКСПРЕССИИ ГЕНОВ – ЭВОЛЮЦИОННЫЙ РЕЗЕРВ АДАПТАЦИОННЫХ ИЗМЕНЕНИЙ МОРФОГЕНЕЗА КОНЕЧНОСТЕЙ НАСЕКОМЫХ//Известия Российской академии наук. Серия биологическая. 2012. № 2. С. 228.

Исследовали гипоморфные мутации генов spineless (ss), Distal-less (Dll), leg-arista-wing complex/TBP-related factor 2 (lawc/Trf2), CG5017 и hsp70 для изучения влияния уровня их экспрессии на формирование дистальных структур антенны и ног Drosophila melanogaster. Продемонстрировано влияние уровня транскрипции генов CG5017, hsp70, Dll и lawc на фенотипическое проявление мутации гена ss, и вовлечeнность этих генов в процесс регуляции морфогенеза конечностей Drosophila melanogaster. Показано, что суммарное понижение уровня экспрессии генов CG5017, hsp70, Dll и lawc способствует потере сегментарного строения дистальных структур ног и антенн и возврату морфогенеза конечностей дрозофилы к эволюционно ранним предшественникам насекомых. Предлагается гипотеза, рассматривающая морфогенез конечностей насекомых как эволюционно-древний процесс построения аморфно-кристалических хитиновых структур с каталитически-модифицирующим участием продуктов экспрессии генов.


У дрозофилы один из генов комплекса lawc/Trf2 (leg-arista-wing complex/TBP related factor 2) кодирует альтернативный фактор базовой транскрипции, гомологичный белку TRF2 позвоночных животных и человека, и принадлежит консервативному семейству генов Tbp (TATA box-binding protein). В данной работе изучали причины высокой частоты нерасхождения хромосом среди потомков мутантов 18 линий со сниженной экспрессией белка TRF2. Было установлено, что подавление экспрессии TRF2 нарушает формирование компактного хромоцентра и правильного сближения гомологичных хромосом как в герминативных, так и в соматических клетках. Обсуждается возможность участия TRF2 в эволюционном генетически запрограммированном процессе нарушения соотношения полов, характерном ряду видов животных.

Гарипова Р.Ф. МУТАГЕННОСТЬ СТОКОВ ОРЕНБУРГСКОГО ГХК И РАСТВОРОВ СОЛЕЙ ТЯЖЕЛЫХ МЕТАЛЛОВ В ТЕСТАХ НА ДРОЗОФИЛЕ//Известия Оренбургского государственного аграрного университета. 2009. Т. 4. № 24-1. С. 201-203.

Проведена эколого-генетическая оценка стоков Оренбургского ГХК и растворов никеля углекислого, меди углекислой, олова двухлористого в модельных экспериментах на дрозофиле. Определено, что основой мутагенности стоков предприятия являются соли никеля и меди, выявлена их способность к аддитивному воздействию в тестах на соматический мозаицизм на крыловых маркерах и тестах на сцепленные с полом рецессивные летальные мутации. В модельном эксперименте установлена мутагенность растворов никеля углекислого и меди углекислой по отношению к гаметам животных объектов.

Данилевская О.Н. МОБИЛЬНЫЕ ГЕНЕТИЧЕСКИЕ ЭЛЕМЕНТЫ ДРОЗОФИЛЫ: ИСТОРИЯ ОТКРЫТИЯ И СУДЬБА ПЕРВООТКРЫВАТЕЛЕЙ//Вавиловский журнал генетики и селекции. 2011. Т. 15. № 2. С. 215-224.

Открытие мобильных генетических элементов дрозофилы является самым значительным и выдающимся достижением советской молекулярной биологии. Именно в СССР впервые были получены прямые молекулярные доказательства перемещения генетического материала у эукариот. В статье рассказывается история открытия, основанная на переписке и личных дневниках непосредственных участников этой работы.

Ермаков Е.Л. СЕЗОННАЯ ДИНАМИКА СЛУЧАЙНОЙ ИЗМЕНЧИВОСТИ КОЛИЧЕСТВЕННЫХ МОРФОЛОГИЧЕСКИХ ПРИЗНАКОВ В ПРИРОДНОЙ ПОПУЛЯЦИИ ДРОЗОФИЛЫ//Известия Иркутского государственного университета. Серия: Биология. Экология. 2010. Т. 3. № 1. С. 76-85.

Природная популяция дрозофилы генетически гетерогенна по случайной изменчивости количественных морфологических признаков. По счетным признакам высокая случайная изменчивость наблюдается летом, низкая - весной и осенью; по мерным - высокая - весной и летом, низкая - осенью. Обнаруженная сезонная динамика случайной изменчивости обусловлена отбором генотипов, детерминирующих высокую и низкую изменчивость. Обсуждаются проблемы влияния генетических и экологических факторов на различные формы изменчивости.


Исследовано влияние снижения доступности Д1-подобного рецептора (DopR) дофамина дрозофилы (кормление мух антагонистом DopR) на уровень синтеза ювенильного гормона (ЮГ) у молодых самок D. melanogaster. В качестве индикаторов уровня синтеза ЮГ использованы уровень деградации ЮГ и уровни активности щелочной фосфатазы (ЩФ) и тирозиндекарбоксилазы (ТДК). Показано, что обработка мух специфическим антагонистом DopR, бутакламолом, вызывает повышение уровня деградации ЮГ и стресс-реактивности системы метаболизма ЮГ, снижение активности и стресс-реактивности ЩФ и повышение активности и стресс-реактивности ТДК. Все это свидетельствует, как показано нами ранее, о снижении уровня синтеза ЮГ у молодых самок дрозофилы со сниженной доступностью DopR. Заключено, что активирующее влияние дофамина на синтез ЮГ у Drosophila опосредуется Д1-подобными рецепторами.


На примере МДГ4 (gypsy) Drosophila melanogaster рассматриваются свойства эндогенных ретровирусов беспозвоночных, относимых к классу эррантивирусов (Errantiviridae, Metaviridae). Обсуждаются пути эволюции ретровирусов беспозвоночных и возможные механизмы их происхождения из ретротранспозонов путем присоединения генов вирусов других систематических групп. Показано, что в обеспечении внутреннего иммунитета против МДГ4 (gypsy)у Drosophila melanogaster важную роль играет локус flamenco.


Изложено представление о том, что процессы кроссинговера и динамики мобильных генетических элементов находятся в тесной взаимосвязи. Поведение мобильных элементов генома влияет на процессы гомологичной рекомбинации как непосредственно в момент активации, так и вследствие изменений, происходящих в геномах в результате активного перемещения автономных нуклеотидных последовательностей.

Копыл С.А., Дубатолова Т.Д., Мариловцева E.В., Омельянчук Л.В. РОЛЬ ГЕНА HRS В ФОРМИРОВАНИИ КРЫЛА DROSOPHILA MELANOGASTER//Генетика. 2012. Т. 48. № 9. С. 1039.

Белок HRS (Hepatocyte growth factor receptor tyrosine kinase substrate) является белком эндосом, функция которого состоит в транспорте рецепторных тирозин-киназ из ранних эндосом в лизосомы. Поскольку рецепторные тирозин-киназы являются участниками различных сигнальных путей, дефекты белка приводят к различным аномалиям развития. Проведенное нами исследование функции гена hrs в развитии крыла дрозофилы подтвердило его участие в процессе формирования D/V границы крылового имагинального диска и позволило показать существование еще одной функции гена hrs – его участие в процессе сужения прожилок крыла (vein refinement). Анализ структуры транскриптов гена hrs позволяет полагать, что за процесс сужения жилок отвечает транскрипт B.

Крысова Л.В., Антосюк О.Н., Марвин Н.А., Марвин А.М. ЭКОЛОГО-ГЕНЕТИЧЕСКИЙ ЭФФЕКТ ФОРМАЛЬДЕГИДА// Аграрный вестник Урала. 2011. № 6. С. 54-56

В статье описан эколого-генетический эффект формальдегида


Представлены результаты морфологического и гибридологического анализа признака половой системы самцов дрозофил группы видов-двойников virilis – наличие микрохет на поверхности полового аппарата самцов (эдеагуса). Показаны наличие специфичной экспрессии исследуемого признака в филадах группы D. virilis, зависимость количества и характера распределения микрохет по поверхности эдеагуса от температуры развития у D. virilis и D. lummei и связь признака с половым поведением дрозофилы. Обнаружено доминирование фенотипа D. lummei у межвидовых гибридов D. virilis ? D. lummei. Для генетического анализа изменчивости исследуемого признака использовались межвидовые гибриды D. virilis и D. lummei. Показано достоверное влияние 2-й и 6-й хромосом на число щетинок эдеагуса у гибридных самцов. Также выявлена зависимость эффектов 2-й и 6-й аутосом на изменчивость исследуемого признака от генетического статуса остальных хромосом (эффект взаимодействия генетических факторов, в данном случае хромосом). Обсуждается адаптивное значение исследуемого признака, связанное с участием в формировании изолирующих барьеров на стадии копуляции

Куликов А.М., Лазебный О.Е., Рыбакова Е.Ю. ОЦЕНКА РАВНОМЕРНОСТИ ХОДА МОЛЕКУЛЯРНЫХ ЧАСОВ В РОДОСЛОВНЫХ ВИДОВ ДРОЗОФИЛ ГРУППЫ VIRILIS//Вестник Московского университета. Серия 16: Биология. 2010. № 4. С. 100-103.

Исследована филогения видов-двойников группы Drosophila virilis на основе изменчивости пяти ядерных и митохондриальных генов: Adh, NonA, Fu, Ras1 и 16S-12S рРНК. Предложена модель для оценки неравномерности накопления замен в филогенетических линиях группы видов по произвольному числу последовательностей ДНК с учетом множественных, параллельных и обратных замен. Реконструированы периоды неравномерного хода молекулярных часов в группе видов virilis и построено филогенетическое дерево данной группы на основе нейтральной изменчивости.


Проведен анализ наследуемости формы основного видоспецифического морфологического признака у дрозофил группы virilis – полового органа самцов. Проанализированы гибридные самцы от скрещиваний D. virilis ? D. lummei и D. virilis ? D. novamexicana. Полученные результаты свидетельствуют о нарастании доли признаков с рецессивным статусом у эволюционно более молодых видов, о роли половых хромосом в реализации доминантного или рецессивного статуса признака. Обсуждается роль аддитивной и эпистатической составляющих общей изменчивости в эволюции статуса доминирования, показанная в ряде известных теоретических моделей и подтверждаемая нашими данными. Обсуждаются литературные данные по стерилизации гибридных самцов в межвидовых скрещиваниях с позиции эволюции доминирования.

Лебедева Л.А., Шапошников А.В., Панов В.В., Шидловский Ю.В. БИОЛОГИЧЕСКИЕ ФУНКЦИИ СИГНАЛЬНОГО ПУТИ JAK/STAT В ОРГАНИЗМЕ ДРОЗОФИЛЫ//Генетика. 2013. Т. 49. № 11. С. 1245.

В обзоре рассмотрены основные биологические процессы в организме дрозофилы, которые находятся под контролем сигнального пути Jak/Stat. Плодовая мушка представляет собой удобный объект для изучения роли этого сигнального пути в различных аспектах онтогенеза.


Ранее нами было показано, что на транскрипцию гена yellow может влиять промотор рядом расположенного гена CG3777, который имеет сходный профиль экспрессии. В настоящем исследовании продолжено изучение функционального взаимодействия промоторов генов yellow и CG3777 в трансгенных линиях дрозофилы. В работе использовано свойство дрожжевого активатора GAL4 не стимулировать транскрипцию с промотора гена yellow, если сайты связывания GAL4 находятся с 3-стороны гена. В результате было показано, что если в трансгенных линиях промотор гена CG3777, длиной 982 пн, встроен в той же ориентации, что и промотор гена yellow, – за сайтами GAL4-активатора, то промотор CG3777 обеспечивает сильную стимуляцию гена yellow GAL4-активатором. Если промоторы генов CG3777 и yellow были встроены в противоположной ориентации, то стимуляция гена yellow GAL4 не наблюдалась. В работе получены дополнительные результаты, которые демонстрируют, что функциональное взаимодействие между промоторами CG3777 и yellow зависит от их взаимной ориентации и положения относительно сайтов связывания GAL4-активатора.

Матвеева А.Д., Ионидес Д., Самсонова М.Г., Райнитц Д. МОДЕЛИРОВАНИЕ МЕХАНИЗМОВ РЕГУЛЯЦИИ ЭКСПРЕССИИ ГЕНА EVEN-SKIPPED У ДРОЗОФИЛЫ//Вавиловский журнал генетики и селекции. 2009. Т. 13. № 1. С. 194-201.

Работа посвящена предсказанию организации 5'-проксимального регуляторного района гена evenskipped (eve) исходя из картин экспрессии репортерного конструкта p1.7eve-lacZ. Для предсказания была использована математическая модель, предложенная в работе Янссенс с соавторами (Janssens et al., 2006). Численные эксперименты, выполненные в этой работе, показали, что наилучшее совпадение решений уравнений модели с экспериментальными данными дает набор из 34 сайтов связывания активаторов Bcd, Hb, Cad и репрессоров Kr, Gt, Kni и Tll. Нами показано, что решения уравнений модели можно улучшить, введя два дополнительных предположения о том, что в силу удаленности сайта H1 от кластера сайтов связывания Bcd фактор Hb, связывающийся с этим сайтом, действует как репрессор и о функциональной значимости сайта связывания транскрипционного фактора Sloppy-paired в исследуемом регуляторном районе гена eve.


Дрозофила (drosophila melanogaster) - небольшое насекомое с коротким жизненным циклом длительностью лишь около двух недель, она недорога для размножения и выведения даже большого количества особей. Короткий цикл развития дрозофилы позволяет проследить влияние электромагнитного излучения на всех стадиях жизненного цикла за небольшой промежуток времени. Простота получения нескольких генераций дрозофилы дает возможность изучить действие исследуемого фактора на протяжении нескольких поколений. Исследовалось четыре поколения дрозофилы, в результате чего определились некоторые закономерности влияния электромагнитного поля на животных. Использовалось низкочастотное ЭМП в 5 Гц и высокочастотное ЭМП в 27 ГГц.

Олейникова Т.Ю., Мельник И.В. ВОЗДЕЙСТВИЕ ЭЛЕКТРОМАГНИТНОГО ПОЛЯ НА ПЛОДОВИТОСТЬ НАСЕКОМЫХ (НА ПРИМЕРЕ DROSOPHILA MELANOGASTER)//Вестник Астраханского государственного технического университета. 2011. № 1. С. 17-19.

14. Олейникова Т.Ю., Мельник И.В. ВОЗДЕЙСТВИЕ ЭЛЕКТРОМАГНИТНОГО ПОЛЯ НА ПЛОДОВИТОСТЬ НАСЕКОМЫХ (НА ПРИМЕРЕ DROSOPHILA MELANOGASTER)//Вестник Астраханского государственного технического университета. 2011. № 1. С. 17-19. Проведенные исследования дают комплексную оценку воздействия электромагнитного поля на плодовитость Drosophila melanogaster. В результате исследования было обнаружено более выраженное влияние высокочастотного электромагнитного поля на онтогенез насекомых. Динамика смертности личинок дрозофилы в низкочастотном электромагнитном поле имела волновой характер. В высокочастотном электромагнитном поле обнаружено приспособление организмов на уровне группы к данному воздействию, причём происходит оно не сразу, а в течение нескольких поколений, стабилизируя величину смертности на определённом значении.

Павлова Н.В., Карагодин Д.А., Байбородин С.И., Баричева Э.М. АНАЛИЗ СТРУКТУРЫ ГЛАЗА МУТАНТОВ ПО ГЕНУ TRITHORAX-LIKE DROSOPHILA MELANOGASTER//Вавиловский журнал генетики и селекции. 2010. Т. 14. № 3. С. 558-568.

Анализ структуры глаза новых мутантов по гену Trithorax like (Trl) D. melanogaster выявил широкий спектр нарушений. В частности, было обнаружено нарушение организации рядов омматидиев, дефекты в структуре омматидия (изменение количества фоторецепторов и конусных клеток), изменения ориентации омматидиев и количества клеток, окружающих омматидии (вторичных и третичных пигментных клеток и клеток, составляющих механо-сенсорные щетинки). Картина нарушений, наблюдаемых у Trl-мутантов, указывает на то, что транскрипционный фактор GAGA, кодируемый геном Trl, участвует в регуляции экспрессии ряда генов, необходимых для развития глаза дрозофилы.

Панов В.П., Таргашин А.В. ЭКОЛОГО-МОРФОЛОГИЧЕСКИЕ ОСОБЕННОСТИ ПОСМЕРТНОЙ БИОДЕГРАДАЦИИ КАРПА// Известия Тимирязевской сельскохозяйственной академии. 2010. № 3. С. 142-146.

В статье приводятся данные экспериментальных исследований о посмертных изменениях (прежде всего в мышцах) и смене различных групп живых организмов в процессе биодеградации карпа в наземных и водных условиях. Наблюдается закономерная смена представителей энтомофауны и микобиоты в процессе деградации организма карпа в наземных условиях, однако отмечены некоторые отклонения от классических схем развития биоты теплокровных животных. Генез почвенной некрофауны проходил по схеме: жуки (сильфиды) > мухи (падальные) > жуки (навозные) > мухи (дрозофилы). Водная схема более проста: мухи (падальные) > мухи (пчеловидки) > комары.


Обнаружили, что бензимидазол и его производные достоверно различаются по способности индуцировать доминантные летальные мутации у Drosophila melanogaster как в полулетальной, так и в нетоксичной дозах. Самцы дрозофилы более чувствительны к мутагенному действию бензими-дазолидов, чем самки. Мутагенность отрицательно коррелировала с величинами молекулярной массы и молекулярного объема и положительно - с величиной энергии гидратации. Кратковременное и долговременное воздействие нетоксичной дозой анализируемых веществ создавало преадаптацию к последующему генотоксическо-му действию соединений в дозе LD50. Выявили возможность преадаптации нетоксичной дозой бензимидазола к генотоксичности его производных.

Сентманат М., Эйч Ванг C., С.Р. Элджин С. РОЛЬ PIPHK СИСТЕМЫ И МОБИЛЬНЫХ ЭЛЕМЕНТОВ В СБОРКЕ ГЕТЕРОХРОМАТИНА (ОБЗОР)//Биохимия. 2013. Т. 78. № 6. С. 735-746

Сохранение стабильности генома эукариот определяется правильным формированием гетерохроматина, обеспечивающим сохранность хромосомных структур в митозе и мейозе, а также сайленсингом потенциально опасных мобильных элементов. Нарушение сборки гетерохроматина может приводить к искажению процессов сайленсинга с пагубными последствиями. Поэтому образование гетерохроматина в строго определенных областях генома является важным процессом. В обзоре рассмотрены процессы формирования гетерохроматина у Drosophila melanogaster, первого модельного организма, у которого описана мозаичность, или вариабельность экспрессии гена от клетки к клетке, обусловленная образованием гетерохроматина. Рассмотрена возможная роль мобильных элементов как генетических детерминант гетерохроматинизации. Обсуждается, каким образом пути сайленсинга с помощью коротких РНК могут участвовать в процессе направленного формирования гетерохроматина.

Сидоров Р.А. ОПУХОЛИ ДРОЗОФИЛЫ//Успехи современной биологии. 2010. Т. 130. № 3. С. 237-246.

Предпринята попытка классификации опухолей дрозофилы и рассмотрены фенотипы, связанные с опухолями имагинальных дисков, мозга, системы крови, половых органов, а также фенотипы трансплантируемых опухолей. Приведены примеры неконтролируемого инвазивного метастатического роста опухолей указанных типов. Рассмотрены модели опухолевой прогрессии на дрозофиле, основанные на комбинации нескольких мутаций в онкогенах и супрессорах опухолевого роста.


Предложена методика электрофоретического определения основных метаболитов триптофана, обладающих нейротоксичными свойствами (кинуренин, 3-гидроксикинуренин и кинуреновая кислота) с УФ-детектированием при 227 нм. Предел обнаружения при соотношении сигнал/шум = 3 составил 0.3 мкг/мл. В качестве биологических объектов исследованы особи Дрозофил. Возможность автоокисления 3-гидроксикинуренина в биологических объектах доказана методом масс-спектрометрии.


Представлен анализ полной последовательности митохондриального (мт) генома D. littoralis. Приведены его основные характеристики, размер, нуклеотидный состав, последовательность генов, а также степень давления стабилизирующего отбора на разные участки генома. Обсуждены особенности структуры белок-кодирующих генов и генов тРНК. Приведена структура некодирующих районов: контрольного района и межгенных спейсеров мтДНК группы virilis. Найдены фрагменты мт-генов atp6 и cox3 в ядерном геноме D. virilis. Эволюционная история митохондриальных и ядерных последовательностей этих генов указывает на то, что процесс образования мт-псевдогенов идет в настоящее время и связан с активностью ретротранспозонов.

Струнов А.А., Онищенко Е.А., Киселева Е.В. ОСОБЕННОСТИ СБОРКИ ЯДЕРНОЙ ОБОЛОЧКИ В ПРОЦЕССЕ МИТОЗА В РАННИХ ЭМБРИОНАХ DROSOPHILA MELANOGASTER//Вавиловский журнал генетики и селекции. 2011. Т. 15. № 4. С. 661-673.

В настоящей работе проведено ультраструктурное исследование ядерной оболочки делящихся ядер эмбрионов дрозофилы на стадии синцитиальной бластодермы. Ранее было показано, что митоз в ранних эмбрионах Drosophila melanogaster является полузакрытым и ядерная оболочка разбирается полностью только на полюсах веретена деления, а в остальных участках формируется двойная (spindle) оболочка (Stafstrom, Staehelin, 1984). Нами установлено, что на стадии метафазы ядерная оболочка разбирается полностью на пузырьки/везикулы и короткие мембраны, формирующие широкий слой вокруг нуклеоплазмы. Сборка ядерной оболочки дочерних ядер начинается на стадии поздней анафазы и сопровождается формированием протяженных стопок мембран шероховатого эндоплазматического ретикулума при участии компонентов предшествующей оболочки. Везикулы и стопки двухслойных мембран располагаются сначала радиально по периферии ядра, а затем перемещаются в нуклеоплазму и тесно контактируют с компактизованными хромосомами. Впервые обнаружено, что новые фрагменты ядерной оболочки могут формироваться с участием везикул и двухслойных мембран вокруг индивидуальных хромосом. Предполагается, что этот процесс наряду с действием других факторов способствует декомпактизации хромосом подобно тому, как это наблюдалось в условиях in vitro. На стадии телофазы происходит полная декомпактизация хромосом, слияние окружающих их мембранных фрагментов и формирование целостных ядерных оболочек вокруг нуклеоплазмы каждого из дочерних ядер.

Сурма С.В., Щеголев Б.Ф., Васильева О.В., Рубанова Н.С., Цырлин В.А. СЛАБЫЕ НИЗКОЧАСТОТНЫЕ ПОЛЯ В БИОЛОГИИ И МЕДИЦИНЕ//Бюллетень Федерального Центра сердца, крови и эндокринологии им. В.А. Алмазова. 2011. № 2. С. 25-29.

Рассмотрены особенности воздействия слабых низкочастотных магнитных полей на биологические объекты. Показано, что высокая проникающая способность в биологические среды и неинвазивный характер воздействия вызывают магнитобиологические эффекты, которые могут быть использованы в практической медицине.

Федоров В.И., Вайсман Н.Я., Немова Е.Ф., Мамрашев А.А., Николаев Н.А. ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ ВЛИЯНИЯ ТЕРАГЕРЦОВОГО ИЗЛУЧЕНИЯ НА СТРЕССИРОВАННЫХ САМОК ДРОЗОФИЛ// Бюллетень медицинских интернет-конференций. 2012. Т. 2. № 6. С. 431-433.

Цель исследования - изучение влияния терагерцового излучения на численность и динамику развития потомства самок дрозофил. Материал - девственные самки дрозофил линии Oregon R. Мух подвергали стрессовому воздействию (ограниченное пространство без корма в течение 2.5 часов). Часть мух при этом облучали генератором терагерцового излучения в диапазоне частот 0.6 - 2.2 ТГц в течение 30 мин. Результаты. Стрессирование отразилось в отклонении динамики созревания потомства до стадии имаго от лабораторного контроля. Терагерцовое облучение оказало разнонаправленное действие: динамика вылета имаго самок приблизилась к лабораторному контролю, численность имаго самцов уменьшилась. Заключение. Терагерцовое излучение вызывает отклонение от теоретически ожидаемого 1:1 расщепления по полу.

Черезов Р.О., Воронцова Ю.Е., Мерцалов И.Б., Куликова Д.А., Симонова О.Б. ВЛИЯНИЕ РНК-ШПИЛЬКИ, СПЕЦИФИЧНОЙ К ГЕНУ LAWC, НА ЭКСПРЕССИЮ ПЕРЕКРЫВАЮЩИХСЯ ГЕНОВ КОМПЛЕКСА LAWC/TRF2 У D. MELANOGASTER//Известия Российской академии наук. Серия биологическая. 2013. № 2. С. 133.

Использована генетическая система генного комплекса leg-arista-wing complex/TBP related factor 2 (Iawc/Trf2) в качестве удобной модели для исследования in vivo особенностей работы разнонаправленных перекрывающихся генов. Созданы линии трансгенных дрозофил, несущих конструкции, способные экспрессировать РНК-шпильку, направленную на посттранскрипционное подавление мРНК гена lawc по пути РНК-интерференции. Попытка искусственного подавления lawc-транскриптов вызвала повышение уровня экспрессии гена lawc в несколько раз. Показано, что изменение концентрации lawc-транскриптов может влиять на концентрацию транскриптов Тrf2. Обсуждаются возможные механизмы регуляции экспрессии исследуемых перекрывающихся генов.


Вирулентность вируса Эбола для морских свинок, появляющаяся в процессе адаптации вируса к этим животным, коррелирует с заменами в гене белка vp24. В частности, при получении штамма 8mc обнаружена замена His > Tyr186. Предпринята попытка выявить функциональную роль этой замены на модели трансгенной плодовой мухи. Используя технику трансформации дрозофилы, получили трансгенные линии, содержащие геномные встройки, кодирующие белок vp24 вируса Эбола дикого типа и мутантный белок с заменой His на Tyr в указанной позиции. Таким образом, получены линии мух, несущие последовательности, кодирующие ген белка vp24 штаммов Заир и 8mc геморрагической лихорадки Эбола в векторе pUAST. Это позволяет исследовать экспрессию трансгенных конструкций в различных органах и тканях Drosophila melanogaster.

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