Том 53, № 3 (2017)

This review presents analysis of the literature and our own research with respect to the role of miRNAs in the regulation of activity (expression) of genes controlling cellular homeostasis in human cells when exposed to ionizing radiation. Human cells, on one hand, can have increased resistance to radiation, which hinders the effectiveness of tumor treatment in radiotherapy. On the other hand, increased sensitivity to radiation may be accompanied by the development of several pathologies, including tumorigenesis. This paper examines the role of specific miRNAs in the formation of radioresistance and radiosensitivity of human cells and their impact on the respective target genes. Separate sections are devoted to the role of different miRNAs in radiation therapy of tumors of different localization, as well as their role in the bystander effect. A special section highlights features of gene activity and its regulators, miRNAs, in radiosensitive cells in patients with Down syndrome. The final section provides information about new approaches to change miRNA expression and, accordingly, their target genes by the action of plant and synthetic drugs (crown compounds) which reduce damaging effects of mutagens. It is assumed that antimutagens affecting the expression levels of miRNAs and structural genes may be used to correct the increase and decrease in cellular radioresponse, reducing the risk of development of pathological processes, including tumorigenesis.

This work represents the results of comparative analysis of the nucleotide sequences in the chromosomal region containing CTXφ prophage in isogenic toxigenic (Tox⁺) and nontoxigenic (Tox^–) strains of Vibrio cholerae biovar El Tor. It is shown that spontaneous mutants which have identical Tox^– phenotype are formed either owing to the precise elimination of CTX_φ prophage from the chromosome (deletion size is 6.9 kb) or owing to imprecise elimination with the additional loss of two other prophages (RS1φ and TLC_φ), which are adjacent to CTX_φ prophage (deletion size is 17.4 kb). It is revealed that, in the nontoxigenic mutants, CTX_φ deletion initiates simultaneous change in several phenotypic properties, which are associated with virulence or biofilm formation, such as colonizing ability, HA/P production, VPS, and motility. For the first time, it is stated that the cause of the pleiotropic effect of the CTX_φ deletion is a cascade decrease in the transcription levels of seven regulatory genes (toxR, aphA, tcpP, tcpH, toxT, vpsT, vpsR) which control virulence and biofilm formation processes in the cholera agent.

A comparative study of wheat–wheatgrass substituted cultivars and lines resistant to leaf rust developed by the Agricultural Research Institute for Southeast Regions (Multi 6R, Belyanka, Favorit, Voevoda, Lebedushka) and Samara Agricultural Research Institute (Tulaikovskaya 5, Tulaikovskaya 10, Tulaikovskaya 100, Tulaikovskaya Zolotistaya) breeding was conducted. A complex analysis using molecular cytogenetic (C-differential banding, fluorescent (FISH) and genomic (GISH) in situ hybridization), molecular (PLUG markers), and biochemical (electrophoretic analysis of gliadins) markers demonstrated that they have a substitition of wheat chromosome 6D by the chromosomes 6Agⁱ and 6Agⁱ2 belonging to the J(=E) Agropyron intermedium (Host) Beauv (=Thinopyrum intermedium (Host) Barkworth & D.R. Dewey) subgenome. In spite of the fact that the chromosomes 6Agⁱ and 6Agⁱ2 differ in the C-banding pattern and demonstrated minor differences in the blocks of gliadin components, they had the identical pattern of pSc119.2 and pAs1 probe distribution and conjugated between themselves with insignificant disturbance. Thus, it was demonstrated that 6Agi and 6Agⁱ2 are homologous chromosomes; however, the question about allelism of their leaf rust resistance genes between themselves requires special studies. Nevertheless, using STS and SCAR markers and taking into account the type of reaction to Puccinia triticina, their non-allelism to the Lr9, Lr19, Lr24, Lr29, Lr38, and Lr47 genes was established. It was revealed that the 6Agⁱ and 6Agⁱ2 chromosomes have a different level of transmission in hybrid F₂ populations depending on the hybrid combination gene background.

Variability of nuclear microsatellite loci was examined in Siberian dwarf pine. Six microsatellite loci (RPS2, RPS6, RPS12, RPS124, RPS127, Pc18) demonstrated different polymorphism levels in ten populations of Siberian dwarf pine. The average number of alleles per locus was 4.88, the average observed heterozygosity was 0.465, and the average expected heterozygosity was 0.510. About 13% of total genetic variability was explained by the genetic differences between the populations (F_ST = 0.129). Genetic distances between the examined populations of Pinus pumila inferred from the data on the SSR marker frequencies statistically significantly correlated with the geographical distances between the population samples. The level of genetic variability of the populations from Kamchatka Peninsula was lower than that demonstrated by continental and island populations. The genetic differentiation of the Kamchatka–Magadan and other populations of Siberian dwarf pine observed in our study can be explained in terms of their formation from different Pleistocene refugial centers.

On the basis of the analysis of genetic variation detectable by ISSR-PCR, the state of the gene pools of 14 populations of Roman snail Helix pomatia L. in the conditions of urbanized landscapes of the southeastern and eastern parts of the current range was examined. According to the data obtained, the majority of the studied populations of this mollusk are in satisfactory condition. This is evidenced by the increased level of genetic diversity (H_e = 0.199 ± 0.025, I_sh = 0.306 ± 0.035) and the high values of effective population size, calculated, on the basis of the straight-line regression equation, between the pairwise genetic and geographic distances (Ne = 2.0–4.9) that are comparable with indigenous common species of terrestrial mollusks. Despite the high level of differentiation (G_st = 0.255, Φ_st = 0.233, N_m = 0.822), the population distribution was not random (R_m =–0.591, p = 0.0004) and corresponded to the model of isolation by distance. It is hypothesized that, in the adventitious colonies of this mollusk, effective formation of a balanced genetic structure takes place that, in the context of biological and ecological features, facilitates its adaptation to the conditions of an urban environment and the population of the new territories of Eastern Europe.

The primary structure of the APC gene DNA was examined in 108 patients younger than 45 years old diagnosed with “familial adenomatous polyposis, classic form” using PCR, conformation-sensitive electrophoresis, and Sanger sequencing. Mutations in the APC gene were observed in 78 patients; de novo mutations were observed in 17 cases. In the majority of cases (n = 45), patients exhibited frameshift mutations, 28 patients had nonsense mutations, and other 5 patients showed splicing mutations. We also revealed recurring variants: p.Arg232X (2 cases), p.Asp849GlufsX11 (2), p.Ser1068GlyfsX57 (2), p.Arg216X (3), p.Gln1062X (5), p.Arg213X (5), and p.Glu1309AspfsX4 (16). It was shown that, compared with other pathogenic variants in the APC gene in Russian patients, mutation p.Glu1309AspfsX4 does not result in earlier development of colorectal cancer and polyps. Nineteen mutations were described for the first time. The identified mutations were located between codons 142 and 1492 of the APC gene. This indicates the importance of investigation of all the gene coding exons. Pathogenic variants were observed in 16 of 35 studied relatives of the mutation carriers. All 16 relatives were included in the “risk group” for lifelong clinical monitoring.

The Upper Volga region was an area of contacts of Finno-Ugric, Slavic, and Scandinavian speaking populations in the 8th–10th centuries AD. However, their role in the formation of the contemporary gene pool of the Russian population of the region is largely unknown. To answer this question, we studied four populations of Yaroslavl oblast (N = 132) by a wide panel of STR and SNP markers of the Y-chromosome. Two of the studied populations appear to be genetically similar: the indigenous Russian population of Yaroslavl oblast and population of Katskari are characterized by the same major haplogroup, R-M198 (xM458). Haplogroup R-M458 composes more than half of Sitskari’s gene pool. The major haplogroup in the gene pool of the population of the ancient town of Mologa is N-M178. Subtyping N-M178 by newest “genomeera” Y-SNP markers showed different pathways of entering this haplogroup into the gene pools of Yaroslavl Volga region populations. The majority of Russian populations have subvariant N3a3-CTS10760; the regular sample of Yaroslavl oblast is equally represented by subvariants N3a3-CTS10760 and N3a4-Z1936, while subvariant N3a4-Z1936 predominates in the gene pool of population of Mologa. This N3a4-Z1936 haplogroup is common among the population of the north of Eastern Europe and the Volga-Ural region. The obtained results indicate preservation of the Finno-Ugric component in the gene pool of population of Mologa and a contribution of Slavic colonization in the formation of the gene pool of the Yaroslavl Volga region populations and make it possible to hypothesize the genetic contribution of the “downstream” (Rostov- Suzdal) rather than “upstream” (Novgorod) Slavic migration wave.

The complete nucleotide sequence of the chloroplast rps2 gene is determined and the polymorphism of this gene in 26 Monotropa hypopitys accessions from the populations of the European part of Russia is analyzed. The studied accessions can be divided into two groups on the basis of the rps2 gene length. In the first group, the rps2 gene sequence length is 711 bp, and in the second group, it is 753 bp. Also, the groups differ from each other by 42 SNPs, which lead to 11 radical and 15 conservative amino acid substitutions in the amino acid sequence of the protein. They also differ in the position of regulatory elements in the 5'-untranslated region of the gene.