[Effect of the histone deacetylase inhibitor sodium butyrate on the viability and life span in Drosophila melanogaster].

Histone acetylation (one of the most important epigenetic mechanisms controlling gene expression) has been recently shown to be involved in life span (LS) determination. There are some data indicating the geroprotective potential of histone deacetylase (HDAC) inhibitors. In the present study, the effects of HDAC inhibitor, sodium butyrate (SB), on the parameters of viability and LS of Drosophila melanogaster were studied. Since SB is an efficient inducer of epigenetic changes, it can be assumed that its use as a life-extending agent (geroprotector) can be quite promising.

[Neuroendocrine system in Drosophila melanogaster lifespan control].

Drosophila is used as a model organism to review the mechanisms of neuroendocrine system involvement in lifespan control. The role of neuron specific expression of genes participating in antioxidative system in lifespan control is described. Data on endocrine function of the nervous system in lifespan control are discussed. The participation of genes involved in the regulation of nervous system development and function in lifespan control is contemplated. Based on the data available, hypotheses considering assembly of neurons as the lifespan limiting tissue and (or) the tissue providing regulation of lifespan via systemic effects on other cell types are evaluated.

[Regularory elements of the copia retrotransposon determine different levels of expression in different organs of males and females of Drosophila melanogaster].

Using a model system in which the expression of the reporter gene lacZ is under the control of five deleted variants of the copia retrotransposon regulatory region, which includes the 5'-long terminal repeat (LTR) and the 5'-untranslated region (5'-UTR), their contribution to the control of retrotransposon activity in different organs of males and females of Drosophila melanogaster was analyzed. The whole regulatory region provides expression of the reporter gene at the embryonic stage, and in larvae and adult flies only in generative organs. The 5'-end of LTR harbors a positive regulator that determines expression of the retrotransposon in organs of all types. The 3'-end of LTR harbors a negative regulator, which is sex- and time-specific: it represses copia expression in generative organs of males at all stages of development, and only at the imaginal stage in somatic tissues, without any effect on the expression of the retrotransposon in females. 5'-UTR contains a negative regulator of copia expression: it decreases the expression in embryos and generative organs and blocks it in somatic tissues. It may be suggested that a complex set of regulatory elements was formed in the course of the evolution of the retrotransposon, which made it possible to maintain a certain level of its expression in different types of cells and tissues and at different stages of development and, thus, to limit the harm caused to the host and provide the possibility for the retrotransposon to exist in the host genome over many generations.

[Molecular variation of the shuttle craft and Lim3 genes, controlling the development of the nervous system, in a natural Drosophila melanogaster population].

Comparative polymorphism of the first exon and first intron of the shuttle craft (stc) and Lim3 genes and their putative regulatory 5'-flanking sequences was analyzed using 20 sequenced natural alleles. A comparison of the stc and Lim3 genes showed that the extent of polymorphism was similar in their introns and corresponded to the variation level characteristic of Drosophila melanogaster, while the putative regulatory region and first intron of the stc gene proved to be more variable than the corresponding regions of the Lim3 gene. Since the genes under study occurred on the same chromosomes isolated from one population and were close together in a region having a high recombination rate, the difference in the extent of polymorphism between the regulatory and coding regions was explained by individual characteristics of each gene. The results made it possible to assume that the extent of polymorphism of the coding gene regions is maintained by balancing selection.

[Genes regulating the development and functioning of the nervous system determine life span in Drosophila melanogaster].

Earlier, it has been shown that genes responsible for differences in longevity between wild-type Drosophila melanogaster lines 2b and Oregon are localized in region 7A6-B2, 36E4-37B9, 37B9-D2, and 64C-65C. Quantitative complementation tests were conducted between the gene mutations localized in these regions and involved in catecholamine biosynthesis (iav (inactive), Catsup (Catecholamines up), amd (alpha methyl dopa resistant), Dox-A2 (Diphenol oxidase A2), pie (pale)) and neuron development control (Fas3 (Fascyclin 3), tup (tail up), Lim3), on the one hand, and two different normal alleles of these genes in lines 2b and Oregon, on the other. Complementation was found for genes iav, Fas3, amd and ple. The remaining genes (Catsup, Dox-A2, tup, and Lim3) are candidate genes for controlling differences in longevity between lines 2b and Oregon.

[Age dependence of the level of copia retrotransposon expression in the testes of Drosophila melanogaster]. / Vozrastnaia zavisimost' ékspressii retrotranspozona copia v semennikakh Drosophila melanogaster.

Expression of the lacZ reporter gene controlled by various deletion derivatives of the regulatory region of the copia retrotransposon was studied in the testes of adult transgenic males of the Drosophila melanogaster y1W67c23(2) strain at the age of 3, 6-9, 12-15, 18-21, and 24-27 days. When the construct contained the full-length regulatory region, which included the 5'-long terminal repeat (LTR) and the 5'-untranslated region (UTR), expression was the lowest in males aged 12-15 days and the highest in males aged 3 or 24-27 days. A similar V-shaped age dependence was previously observed for the copia transposition rate and RNA content in a strain with a high rate of copia transposition. Thus, the V-shaped age dependence of expression, which is unusual for Drosophila, proved to be characteristic of copia regardless of its transposition rate. Deletion of the 5' or 3' end of the LTR, but not of the UTR, changed the age dependence of the level of reporter gene expression. In this case, expression was the highest in 3-day-old males and gradually decreased with age, as typical for many Drosophila genes. It was assumed that the 5'- and 3'-terminal regions of the copia LTR contain regulatory elements responsible for the V-shaped age dependence of expression, while the expression level depends to a greater extent on the regulatory elements of UTR.

[Regulatory elements of copia retrotransposons, controlling the level of its expression in Drosophila melanogaster testes]. / Reguliatornye élementy retrotranspozona copia, kontroliruiushchie uroven' ego ékspressii v semennikakh Drosophila melanogaster.

Expression of the lacZ reporter gene under the control of five deletion derivatives of the copia regulatory region including the 5' long terminal repeat (LTR) and the 5' untranslated region (UTR) was assayed in the testes of transgenic Drosophila melanogaster males (larvae and imago). The full-length copia regulatory region (LTR + UTR) ensured expression of the reporter gene in testes of both larvae and adult males. Deletion of UTR or 3' end of LTR increased lacZ expression in the testes, whereas deletion of the 5' end of LTR increased it. This indicated that a positive regulator of copia expression is at the 5' end of LTR and that negative regulators are at the 3' end of LTR and in UTR. The effects of the fragments of the copia regulatory region on reporter gene expression in the testes in vivo did not completely coincide with the effects observed earlier in cultured cells. We suggest that this difference is due to different regulation of expression of the fusion constructs integrated into chromatin as compared to their transient expression.

[Variability of localization of retrotransposon copia ant its effect on adaptation in inbred strains of Drosophila melanogaster with the different rate of transposition]. / Izmenchivost' lokalizatsii retrotranspozona copia i ego vliianie na prisposoblennost' v inbrednykh liniiakh Drosophila melanogaster, kharakterizuiushchikhsia razlichnoi chastotoi transpozitsii.

Three sublines of an inbred laboratory line of Drosophila melanogaster with the initial copia transposition rate 2 x 10(-2), 2 x 10(-3), and 5 x 10(-4) per copy per generation were reared for several dozen generations under conditions of low effective population size (by full-sib crosses or in a small mass culture of 10 females x 10 males). All six lines were tested for the transposition rate, location pattern, and copy number of copia in euchromatic genome regions and for fitness inferred from the intraspecific competition index. The copia transposition rate remained constant in both versions of the lines with an initially lower rate and decreased by an order of magnitude in both versions of the line with an initially higher rate. New copia insertions behaved as selectively neutral and were accumulated in the genome. Each new copy decreased fitness by less than 1% on average. Some of the existing unfixed insertions remained segregating after long-term inbreeding and were assumed to provide a selective advantage to heterozygotes.

[Genomic factors regulating the transposition of drosophila mobile elements]. / Genomnye faktory, reguliruiushchie transpozitsii mobil'nykh élementov drozofily.

Data on regulation and genetic control of transposition of mobile genetic elements (ME) in Drosophila are reviewed with special emphasis on the most abundant and best studied class of ME, retrotransposons. The effects of cis- and trans-acting factors on their expression are analyzed. Loci of the host genome involved in regulating their transposition are considered.

[Correlation between the number of sites, transcript levels and transposition frequency of retrotransposon copia in Drosophila melanogaster]. / Korreliatsiia mezhdu chislom saitov, kolichestvom transkripta i chastotoi transpozitsii retrotranspozona copia u Drosophila melanogaster.

Numbers of copia transcripts in testes of files from five Drosophila melanogaster lines were compared by means of Northern blot hybridization. Four of these lines were closely related differing only by transposition rates and the number of copia sites in the genome. The fifth line, which was not related to the others, was characterized by lack of transpositions and the lowest copia copy number. Positive correlation between total copia transcript level and its copy number and transposition rate was observed. Therefore, transcription rate of copia retrotransposon in tests is largely controlled by the level of its transcription, which, in turn, is regulated by the number of retrotransposon copies in the genome. These data contradict the hypothesis on self-regulation of retrotransposon copy number in the genome.

["Adaptive transposition" of retrotransposons in the Drosophila melanogaster genome accompanying the increase in features of adaptability]. / "Adaptivnye transpozitsii" retrotranspozonov v genome Drosophila melanogaster, soprovozdaiushchiesia uvelicheniem presposoblennosti osobei.

Two cases of spontaneous transpositions of MDG1, MDG3, and copia retrotransposons were detected in Drosophila melanogaster lines derived from the nonadaptive NA line and marked by recessive visible mutations. The transpositions were accompanied by a dramatic increase in individual fitness (competitive success). In independent instances of MDG1 transpositions, the location patterns of new sites were similar. These results confirm the existence of adaptive transpositions that were demonstrated earlier for the NA line that carried no visible markers.

[Mobilization of retrotransposon copia in the Drosophila melanogaster genome]. / Mobilizatsiia retrotranspozon copia v genome Drosophila melanogaster.

Considerable heterogeneity of retrotransposon copia sites of location on polytene chromosomes was revealed in one of the substocks of the inbred Drosophila melanogaster stock. Heterogeneity of copia sites of location was found in no other substocks analyzed. The heterogeneity was shown to be caused by copia insertions in new sites. The frequency of insertions is about 12% per haploid genome per generation. The retrotransposon excisions and somatic transpositions were not observed. The location of retrotransposons mdg1, mdg2, mdg3, mdg4, 297 and H.M.S. Beagle appeared to be stable in all the stocks analyzed. Thus, a model system allowing to study mechanisms of retrotransposon copia transpositions in D. melanogaster tissues as well as phenotypic effects of copia mobilization is described.

[Comparative analysis of the localization and mobility of retrotransposons in sibling species Drosophila simulans and Drosophila melanogaster]. / Sravnitel'nyi analiz lokalizatsii i podvizhnosti retrotranspozonov u vidov-bliznetsov Drosophila simulans i Drosophila melanogaster.

The distribution of four retrotransposon families (MDG1, MDG3, MDG4 and copia) on polytene chromosomes of different (from 9 to 15) Drosophila simulans strains is studied. The mean number of MDG1 and copia euchromatic hybridization sites (3 sites for each element) is drastically decreased in D. simulans in comparison with D. melanogaster (24 and 18 sites respectively). The mean number of MDG3 sites of hybridization is 5 in D. simulans against 12 in D. melanogaster. As for MDG4 both species have on the average about 2-3 euchromatic sites. The majority of MDG1 and copia and about a half of MDG3 euchromatic copies are localized in restricted number of sites (hot spots) on D. simulans polytene chromosomes. In D. melanogaster these elements are scattered along the chromosomes though there are some hot spots too. It appears that euchromatic copies of MDG1 and copia are considerably less mobile in D. simulans in contrast to D. melanogaster. Some common hot spots of retrotransposon localization in D. simulans and D. melanogaster were earlier described as intercalary heterochromatin regions in D. melanogaster. The level of interstrain variability of MDG4 hybridization sites is comparable in both species. Comparative blot-analysis of adult and larval salivary gland DNA shows that MDG1 and copia are situated mainly in euchromatic regions of D. melanogaster chromosomes. In D. simulans genome they are located mainly in heterochromatic regions underreplicated in salivary gland polytene chromosomes. There are interspecies differences in the distribution of retrotransposons in beta-heterochromatic chromosome regions.

[A new approach to polygene mapping. Localization of genes, controlling the adaptation level of closely related lines of Drosophila melanogaster]. / Novyi podkhod k kartirovaniiu poligenov. Lokalizatsiia genov, kontroliruiushchikh uroven' prisposoblennosti blizkorodstvennykh linii Drosophila melanogaster.

The phenomenon of hitch-hiking of dispersed mobile elements (molecular markers) is proposed as a new approach to polygene mapping. Retrotransposons MDG1 and copia are used as molecular markers to reveal chromosome 2 segments controlling high fitness level in Drosophila melanogaster. Comparison of closely related Drosophila melanogaster stocks with different fitness level demonstrates the role of pericentromeric region of chromosome 2 in the control of adaptive value.

[Transposition of mobile dispersed genes (MDG) after substitution of various chromosome pairs in inbred Drosophila melanogaster strains]. / Transpozitsiia mobil'nykh dispergirovannykh genov (MDG) pri zameshchenii otdel'nykh par khromosom v inbrednoi linii Drosophila melanogaster.

Transpositions of MDG-1, MDG-3 and copia were detected as a result of crosses of the inbred maladaptive LA stock with laboratory stocks, in order to construct the genomes carrying different combinations of the LA or non-La chromosomal pairs. Changes of the mobile gene distributions were revealed in chromosomes of hybrid genotypes, as compared to parental chromosomal pairs. A trivial source of variability of chromosomal molecular structure ensured by crossing over was excluded by inversions which serve as suppressors of crossing over in corresponding crosses. Multiple transpositions of mobile genes in definite chromosomal sites were detected in genotypes carrying chromosomal pair 2 originated from the LA stock. No such transpositions were observed, when the pair 2 was substituted by the chromosome 2 originated from the Swedish-b line or in control crosses, where the LA stock was not involved. Both LA chromosomes 2 and 3 were shown to be the targets of transpositions. Comparison of hot spot transposition sites of MDG-1, as a result of crosses, with the earlier described rare events of spontaneous transpositions in the LA stock, coupled with its fitness increase, revealed that the hot spot sites were shared in both series of experiments. The data obtained show that transpositions of mobile genetic elements may change the genetic and molecular structure of the chromosome involved in crosses, in spite of suppression of crossing over by inversions usually suggested as a tool for keeping chromosomal genetic structure intact.