Moenomycins (Mm) - phosphoglycolipid compounds produced by ATCC14672 - are considered a promising model for development of novel class of antibiotics. In this regard it is important to generate Mm overproducing strains which would be a basis for economically justified production of this antibiotic. In this work a set of genes for synthesis and reception of low-molecular weight signaling molecules (LSM) in ATCC14672 were described and their significance for Mm production was studied. The ATCC14672 genome carries structural and regulatory genes for production of LSMs of avenolide and γ-butyrolactone families. Additional copies of LSM biosynthetic genes and did not alter the Mm production level. ATCC14672 LSMs are not capable of restoring the sporulation of butyrolactone-nonproducing mutant of . Likewise, while the heterologous host 1326 produced Mm, its mutant M707 (deficient in the butyrolactone synthase gene ) did not. Thus, while the natural level of LSMs production by ATCC14672 does not limit Mm synthesis, the former is essential for the synthesis of moenomycins.

Moenomycins (Mm) are family of phosphoglycolipid natural products that is considered a blueprint to develop new class of antibiotics. The natural Mm producer, (ATCC14672), produces very low amounts of moenomycin, fueling the investigations on genetic approaches to improve its titers. Heterologous expression of moenomycin biosynthesis gene cluster () would be one of the ways to reach this goal. Here we report the generation of a number of novel heterologous streptomycete hosts producing nosokomycin A (one of the members of Mm family), and determine their potential for the antibiotic production. The point mutation in the model strain of genetics, (strain M1152) significantly improved nosokomycin A production compared to parental strains (M145 and M512), while double mutation in the same species (strain M1154) decreased it. Our results point to the previously unanticipated epistatic interactions between mutations that individually are known to be highly beneficial for antibiotic production. We also showed here for the first time that facultative chemolitotrophic streptomycete and chloramphenicol producer can be used as the hosts for genes.

The authors' studies on the organization and variation of plant genome with the use of molecular markers are briefly reviewed with special emphasis on random amplified polymorphic DNA (RAPD), inter simple sequence repeat (ISSR), sequence characterized amplified region (SCAR), and cleaved amplified polymorphic sequence (CAPS) markers detected with the use of polymerase chain reaction (PCR). These markers have been demonstrated to be promising for identifying cultivars and determining the purity of genetic strains of pea. Genetic relationships between strains, cultivars, and mutants of pea have been studied. The role of molecular markers in molecular genetic mapping and localizing the genes of commercially important characters of pea has been shown. The possibility of the use of molecular markers for studying somaclonal variation and detecting mutagenic factors in plants during long-term spaceflights is considered. The prospects of using DNA markers for understanding the organization and variability of higher plant genomes are discussed.

The study of Balkan endemic nephropathy (BEN) in the affected localities of southern Serbia shows population-genetic difference between samples of BEN affected individuals and control group consisting of non-affected individuals from the same localities. Detailed population-genetic study in village Chepure, which includes 20 large families where BEN is present in 646 (from first to fourth degree) relatives of probands, shows a familial character of disease as well as significant genetic influences in expression of the illness. Our study of genetic homozygosity degree includes an analysis of the presence, distribution and individual combination of 20 to 30 selected genetically controlled morphophysiological traits in the sample of BEN patients and in the control-healthy group. Assuming that BEN is genetically controlled disease, we made a hypothesis that an increased homozygosity level, as well as the changed variability among the patients, could be populationgenetic parameter for the prediction of the illness. Taking into consideration our experience, as well as the experience of numerous scientists who studied the nature of the inheritance of mono-and oligo-genically controlled qualitative traits, we applied a methodology to estimate the proportion of such homozygously recessive characters (HRC-test). This population-genetic study did not only show statistically significant difference of the mean values of genetic homozygosity (BEN: 8.7 ± 0.3; control: 7.6 ± 0.3), but of the differences in the type of distribution too, as well as the differences in the presence of certain individual combinations of such traits.

The tandem of humanized variable VL and VH genes (ScFv fragment 4D5) possessing a high affinity to the HER-2/neu oncogene (the epidermal growth factor receptor expressed in many types of human tumors) was attached through a flexible linker to the second exon of human antibodies of IgG or IgE isotypes constant gene. The humanized construct of IgE isotype was generated for the first time. Genes of the recombinant antibodies were cloned into the pCl-neo vector under the control of universal cytomegalovirus (CMV) promoter. Transfected HEK-293 cells efficiently produced antibodies of the corresponding isotypes IgE and IgG1. The results of Western blotting confirmed homogeneity of the expressed antibodies, which had the predicted molecular weight and specifically interacted with the HER-2/neu. The attachment of leader peptide to the 5'-end of the gene resulted in the preferential accumulation of recombinant antibodies in the cultural medium. These results indicate that de novo constructed humanized immunoglobulin genes express functionally active, single-chain recombinant antibodies in eukaryotic cells.

Studies in which individuals carrying transgenes of animal viruses were used to analyze the action of animal viral proteins on the cell are reviewed. The data presented suggest that host specificity of viruses is determined by their proteins responsible for the penetration of the virus into the cell, while viral proteins responsible for interactions with the host cell are much less host-specific. Due to this, the model of with its developed system of searching for genetic interactions can be used to find intracellular targets for the action of viral proteins of the second group.

In 2019, the SARS-CoV-2 beta-coronavirus, which caused a pandemic of severe acute respiratory viral infection COVID-19 (from COronaVIrus Disease 2019), was first detected. The susceptibility to SARS-CoV-2 and the nature of the course of the COVID-19 clinical picture are determined by many factors, including genetic characteristics of both the pathogen and the human. The SARS-CoV-2 genome has a similarity to the genomes of other coronaviruses, which are pathogenic for humans and cause a severe course of infection: 79% to the SARS-CoV genome and 50% to the MERS-CoV genome. The most significant differences between SARS-CoV-2 and other coronaviruses are recorded in the structure of the gene of the S protein, a key protein responsible for the virus binding to the receptor of the host organism cells. In particular, substitutions in the S protein of SARS-CoV-2, leading to the formation of the furin cleavage site that is absent in other SARS-like coronaviruses, were identified, which may explain the high pathogenicity of SARS-CoV-2. In humans, the genes that are significant for the initial stages of infection include , , (encode receptors for coronavirus binding); , , , , (encode proteases involved in the entry of the coronavirus into the cell); (the gene of ATP-dependent RNA helicase DDX1, which promotes replication of coronaviruses); and , , and (encode interferon-induced transmembrane proteins with an antiviral effect). These genes are expressed in many tissues (including those susceptible to the effects of SARS-CoV-2); rare and frequent variants that affect the structure of the encoded protein and its properties and expression level are described in them. A number of common genetic variants with proven functional significance are characterized by the variability in the allele frequency in the world's populations, which can determine interpopulation differences in the prevalence of COVID-19 and in the clinical features of the course of this pathology. The expression level of genes that are important for the formation of the susceptibility to SARS-CoV-2 is affected by epigenetic modifications, comorbidities at the time of infection, taking medications, and bad habits.

The COVID-19 coronavirus pandemic has spread to 215 countries around the world and caused tens of millions of infections and more than a million deaths worldwide. In the midst of COVID-19 infection, it is extremely important to identify new protein and gene targets that may be highly sensitive diagnostic and prognostic markers of the severity and outcome of the disease for combating this pandemic. Identification of individual genetic predisposition allows personalizing programs of medical rehabilitation and therapy. It has now been shown that the transmissibility and severity of COVID-19 infection can be affected by gene variants in both the human body (, , γ, , , TNFA, IL6, blood group A antigen, etc.) and the virus itself ( in RNA polymerase, in RNA primase, S, N, E proteins). The presence of mutations in the proteins of the virus can change the affinity and specificity for the binding of targeted drugs to them, being the molecular basis of individual differences in the response of the human body to antiviral drugs and/or vaccines. The review summarizes the data on the variants of the genomes of the coronavirus and humans associated with an individual predisposition to an increased or decreased risk of transmission, severity, and outcome of COVID-19 infection. Targeted drugs and vaccines being developed for the therapy of COVID-19 infection are briefly reviewed.

Cross-replicating associations with rs657152 at the 9q34.2c locus and rs11385942 at the 3p21.31 locus found in patients with severe COVID-19 in the Caucasian population require the study of the discovered phenomenon in various populations, including as an independent biological marker. Primers and TaqMan probes for PCR discrimination of the A and C alleles in single nucleotide polymorphism (SNP) rs657152 have been developed. The polymorphism of the rs657152 A/C locus was determined in 129 patients with COVID-19 and in a control group of 466 healthy individuals. There were no significant differences in the frequency of distribution of the A and C alleles, 0.47/0.53 and 0.45/0.55, between patients and healthy subjects, respectively. Also, no differences were found in the distribution of alleles in patients with a high viral load in the smear (Ct in the range of 16-25) in comparison with an average and low viral load (Ct in the range of 26-40).

The changes in the telomere length caused by the terminal underreplication in the existing literature are related to depressive disorders. However, the use of the telomere length as a biomarker of depressive states is ambiguous, which is due to the effect of various environmental factors on both the psychoemotional state and cellular aging of an organism. In order to identify the possible use of the relative telomere length (RTL) measured in peripheral blood leukocytes as a biomarker of enhanced liability to depression prior to the clinical symptoms, as well as to determine the link between telomere length, sociodemographic factors, allelic variants of the genes involved in the regulation of telomere elongation, and depression level, the association analysis of reverse transcriptase ( rs7726159), telomerase RNA component ( rs1317082), and the CST complex encoding protein ( rs2487999) gene polymorphisms was performed with RTL and depression level in mentally healthy individuals ( = 1065) aged 18-25 years. Together with genetic variants, the examined regression models included various sociodemographic parameters as predictors. As a result of statistical analysis, we failed to observe the association between RTL and individual differences in depression level in the studied sample. Nevertheless, multiple regression analysis allowed us to construct a statistically significant model of individual variance in RTL ( = 4.3е-4; = 0.018), which included rs7726159 in the gene ( = 0.020; β = 0.078) and such environmental predictors as age ( = 0.001; β = -0.027) and place of residence in childhood (urban/rural area) ( = 0.048; β = 0.063). The data obtained confirm the involvement of gene variants and age in telomere length in mentally healthy individuals aged 18-25 years and indicate a negative effect of urban residency on telomere length shortening, which reflects the cellular aging of an organism.

Aging is a natural process of extinction of the body and the main aspect that determines the life expectancy for individuals who have survived to the post-reproductive period. The process of aging is accompanied by certain physiological, immune, and metabolic changes in the body, as well as the development of age-related diseases. The contribution of genetic factors to human life expectancy is estimated at about 25-30%. Despite the success in identifying genes and metabolic pathways that may be involved in the life extension process in model organisms, the key question remains to what extent these data can be extrapolated to humans, for example, because of the complexity of its biological and sociocultural systems, as well as possible species differences in life expectancy and causes of mortality. New molecular genetic methods have significantly expanded the possibilities for searching for genetic factors of human life expectancy and identifying metabolic pathways of aging, the interaction of genes and transcription factors, the regulation of gene expression at the level of transcription, and epigenetic modifications. The review presents the latest research and current strategies for studying the genetic basis of human aging and longevity: the study of individual candidate genes in genetic population studies, variations identified by the GWAS method, immunogenetic differences in aging, and genomic studies to identify factors of "healthy aging." Understanding the mechanisms of the interaction between factors affecting the life expectancy and the possibility of their regulation can become the basis for developing comprehensive measures to achieve healthy longevity.