卷 55, 编号 3 (2019)

Epigenetic modifications in neurodegenerative diseases are just beginning to be studied; however, the growing interest in this phenomenon indicates its great importance in molecular mechanism of diseases and their phenotypical realization. DNA methylation takes one of the central places in gene expression regulation. This review considers the main DNA methylation types and the mechanisms of methylation and demethylation and provides general information on epigenetic regulation in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and hereditary ataxias. Possible prospects for targeted epigenetic correction as a new approach to neurodegenerative disease therapy are discussed.

In D. melanogaster, the nuclear matrix protein EAST functionally interacts with the Su(Hw)-dependent insulator complex. The y² allele, in which the MDG4 retrotransposon is inserted between enhancers and the gene promoter, was previously described. The Su(Hw) insulator sequence is present in the regulatory region of MDG4. An increase in the EAST protein concentration or inactivation of the Mod(mdg4)-67.2 protein, which is part of the Su(Hw)-dependent complex, results in tissue-specific repression of the yellow gene in the y² allele. In the present work, the degree of EAST-dependent and Su(Hw)-dependent repression in different regions of the genome was analyzed using transposition of transgenes containing long terminal repeat (LTR) sequences of the MDG4 retrotransposon and the Su(Hw) insulator. As a result of genetic experiments, it was shown for the first time that EAST-dependent repression of the yellow gene is observed in the same transgenic lines of D. melanogaster as Su(Hw)-dependent repression. The obtained data confirm our earlier suggestion that the regulatory complex, which is formed on the LTR sequence and functionally interacts with the EAST protein, transfers the transgene to the nucleus regions with a high concentration of factors that repress transcription.

We implemented genome-wide expression profiling to identify the mechanisms of toxicity of an organoselenium compound bis(2-pyridine-1-oxide) diselenide to the fungus А. oryzae RIB40. We uncovered changes in the expression levels in 72 genes. In particular, we observed a downregulation in the levels of several copper ion transmembrane transporter genes. In turn, we found a significant upregulation in the genes encoding oxidoreductases. The latter results are supported by biochemical experiments that revealed an increase in oxidoreductase activity in response to bis(2-pyridine-1-oxide) diselenide treatment. The results of a large-scale microarray analysis of the А. oryzae RIB 40 were confirmed by real-time quantitative PCR.

Starch gel electrophoresis was used to study polymorphism of hordeins encoded by the Hrd A and Hrd B loci in 34 local varieties of cultivated barley and 19 accessions of wild barley from Jordan. Thirty-two and 26 alleles for the Hrd A locus were identified in H. vulgare and H. spontaneum, respectively, and 42 and 32 alleles were detected for the Hrd B locus. Allelic frequencies of the Hrd A and Hrd B loci in cultivated barley varied within the range of 0.0029–0.2707 and 0.0029–0.1824, respectively, and within the range of 0.0105–0.1263 and 0.0105–0.0947 in wild barley. Six out of 52 alleles of Hrd A and four out of 70 alleles of Hrd В were common between Jordanian H. spontaneum and H. vulgare. Two of six common alleles of the Hrd A locus found in Jordanian wild and cultivated barley and one common allele of the Hrd В locus were discovered earlier among H. spontaneum accessions from Iran, Turkey, and Syria. However, three common alleles of Hrd A and three common alleles of Hrd В were detected only in Jordanian accessions of wild and cultivated barley. According to archaeological records, the earliest indications of barley utilization in Jordan appeared only in 6700 BC, whereas they were dated in Syria to 9000 BC and in Israel to 17 000 BC. We concluded that Jordan cannot be considered as domestication center of barley. At the same time, Jordanian H. spontaneum could have contributed some alleles of hordein-coding loci to the gene pool of H. vulgare owing to introgression resulting from spontaneous hybridization over the course of crop diffusion from the domestication center outward.

Non-host resistance (NHR) is a plant defense system against the majority of microbial pathogens. Blumeria graminis f. sp. hordei (Bgh), is an obligate biotrophic ascomycete fungal pathogen that can grow and reproduce only on living cells of wild or domesticated barley (Hordeum sp.).‎ In this study, the expression pattern of eight defense-related genes including NPR1, PR2, PR5, PR1-2, Lipase, LTP, PAL and POX was assessed in bread wheat (Triticum aestivum cv. Darya) against the powdery mildew fungus Bgh. Hydrogen peroxide (H₂O₂) activity in leaf tissues was also detected histochemically with 3,3-diaminobenzidine (DAB) staining. Result showed that in response to virulence agent, Bgh spores, papillae and hypersensitive response (HR) were formed in the 53.9 and 40.1% of infected area, respectively while in the rest of the infected area (6%) spores were not germinated. According to the histochemical analysis, the wheat NHR against Bgh belongs to type IІ NHR and display a multi-layered feature including wax composition, pre-formed barriers, papilla formation, hypersensitive response. According to results of expression analysis, the Pox, PR5 and PR1-2 expression level were clearly upregulated 24 hours post inoculation (hpi) and LTP was identified as an early signaling response to Bgh. In this study NPR1 was down regulated during all given time points, thus we suggested that salicylic acid (SA) signaling pathway may be mediated by a NPR1-independent mechanism(s) in wheat-Bgh interaction. The coordinated induction of a set of so-called systemic acquired resistance (SAR) genes including POX, PR1-2 and PR5 was observed in wheat-Bgh interaction. Expression pattern of defense-related genes at the wheat-Bgh interaction can be taken as an indication of their functional relevance at different time points of tissue infection.

On the basis of the allelic composition of ten microsatellite loci and mtDNA sequences, we studied the genetic structure of the common hamster populations that inhabit cities and suburban settlements in Ciscaucasia. It was shown that, in urbanized territories, the hamster population is divided into separated groups, the genetic differences between which are high and not related to the distance between them. On the outskirts of cities adjacent to undeveloped or green areas and further in rural areas, the degree of isolation of neighboring hamster settlements decreases, and the level of genetic differences between them begins to correspond to the distance separating the settlements. In the course of work, this species was first registered within the territory of the easternmost part of Ciscaucasia, in the Republic of Dagestan.

Mitochondria are the energy factory in cells, and more than 95% of the energy in cells is produced by the mitochondrial oxidative phosphorylation (OXPHOS). Therefore, mitochondria likely plays an important role in the process of high-altitude adaptation. Wild Drosophila melanogaster population structure provides a good precondition to detect positive selection on mitochondrial genes related to environmental or climatic variation, specifically hypoxia and high altitudes. In this paper, we sequenced atp6 (ATPase synthase 6) from 27 individuals and cox3 (cytochrome c oxidase III) from 26 individuals of wild Drosophila melanogaster. The percent G+C content of atp6 and cox3 genes has a value of 24 and 29.3%, respectively, exhibiting an extreme bias in base composition. 5 single nucleotide polymorphisms (SNPs) were detected and 2 nonsynonymous substitutions (m.555T > A and m.577A > G) were detected in atp6, only one SNP (m.126C > T) was found from highland Drosophila melanogaster. 6 SNPs were detected in cox3, we found 2 nonsynonymous substitutions (m.745G > A and m.427G > A) of only one highland strain from Yun Nan province. Substitution rates and dN/dS ratios were relatively high for cox3 (ω = 0.34851) compared to atp6 (ω = 0.07329), both of them inferring is purifying selection by using PAML. Only one amino acid site 255I (p < 0.01) of the cox3 gene was found in one fly from low altitude Drosophila sample, which was generated by SNPs (m.763A > G and m.764T > C). From these analyses we conclude that selection may not have played a role in shaping Drosophila melanogaster regional mtDNA variation, the changes in selection is very likely due to some environmental stressors other than hypoxia and high altitudes, and more broadly, our results add to an emerging body of research in Drosophila.

Tick-borne encephalitis (TBE) is caused by a neurotropic RNA virus from the Flavivirus genus. TBE is characterized by a significant variability of clinical manifestations from nonparalytic forms (fever, meningitis) to severe paralytic (focal) forms (meningoencephalitis, poliomyelitis, polioencephalomyelitis). The result of interaction between a virus and a host (and, consequently, the viral disease course and outcome) largely depends on genetically determined ability of the host (particularly, human) organism immune system to suppress the development of viral infection. However, hereditary predisposition to TBE has been rather poorly studied in human populations. In this study, the results of whole exome sequencing of DNA samples from 22 Russian non-immunized TBE patients with severe TBE forms and 17 control individuals from the same populations are presented. Sixteen single nucleotide polymorphisms (SNPs) associated with predisposition to severe forms of TBE were identified. The genotype and allele frequencies for three of these SNPs localized in the ABCB9 (rs4148866, G/A, intron), COL22A1 (rs4909444, G/T, Ala938Asp), and ITGAL (rs1557672, G/A, intron) genes were then studied in larger samples of patients with different forms of TBE (n = 177) and in the control population (n = 215). As a result, the association of the ABCB9 and COL22A1 gene SNPs with the development of severe forms of TBE was for the first time demonstrated in the Russian population. The hypothesis regarding a possible mechanism of the effect of the ABCB9 gene intronic SNP on the process of human infection with TBE virus is considered.

Comparative bioinformatic analysis of sciatic nerve transcriptomes of C57BL/6J mice was carried out. Animals were divided into three groups: Flight, 30-day spaceflight; Recovery, 30-day spaceflight with subsequent 7-day readaptation; and Control. A significant pool of genes with an absolute difference in expression of more than 32 times compared to the control group was revealed in mice after the 30-day spaceflight (Flight and Recovery groups). Comparative analysis of the Flight and Recovery groups of murine transcriptomes did not reveal any significant differences in gene expression. In animals after spaceflight on board the biosatellite, using the KEGG database (Kyoto Encyclopedia of Genes and Genomes), we identified genes related to the state of metabolic and signaling pathways involved in actin cytoskeleton regulation, regulation of potential-dependent calcium, sodium, and potassium channels, and myelination of nerve fibers.

The expression product of the Pax3 gene is a transcription factor involved in the process of neural crest’s stem cell differentiation into melanocytes during embryonic development. In individual life, the Pax3 gene expression is an element of the complex process of regulation the degree of melanoblasts differentiation. The state of melanoblasts (being a reservoir of renewable cells) differentiation depends on UV radiation, which stimulates the Pax3 gene expression. In the absence of radiation the expression of the Pax3 gene is inhibited, what stops the melanoblasts at the current level of diversity. Pax3 gene is one of the candidate genes responsible for animals coat color and its mutations are considered a possible cause for the occurrence of the color patterns: “splashed white” and “white spotting” in Quarter Horse breed. The 5'UTR exon 1 and the intron fragment 1 of the Pax3 gene in the American mink were sequenced. Two variations were found: substitution c.-17G>A in the 5′ UTR and substitution c.+142C>G in intron 1. Investigations were carried out on 93 individuals, which were genotyped for polymorphisms in the 5'UTR region using the MTPA-PCR technique. It was established that the study group was in a state of genetic equilibrium, because there were no statistically significant differences between observed genotypes frequency and theoretically calculated according to the Hardy–Weinberg principle and it was found that there were no statistically significant relationship between the Pax3 gene polymorphism and the American mink coat color.