ARGO: a web system for the detection of degenerate motifs and large-scale recognition of eukaryotic promoters

Reliable recognition of the promoters in eukaryotic genomes remains an open issue. This is largely owing to the poor understanding of the features of the structural–functional organization of the eukaryotic promoters essential for their function and recognition. However, it was demonstrated that detection of ensembles of regulatory signals characteristic of specific promoter groups increases the accuracy of promoter recognition and prediction of specific expression features of the queried genes. The ARGO_Motifs package was developed for the detection of sets of region-specific degenerate oligonucleotide motifs in the regulatory regions of the eukaryotic genes. The ARGO_Viewer package was developed for the recognition of tissue-specific gene promoters based on the presence and distribution of oligonucleotide motifs obtained by the ARGO_Motifs program. Analysis and recognition of tissue-specific promoters in five gene samples demonstrated high quality of promoter recognition. The public version of the ARGO system is available at and

Molecular evolution of the hyperthermophilic archaea of the Pyrococcus genus: analysis of adaptation to different environmental conditions

<p>Abstract</p> <p>Background</p> <p>Prokaryotic microorganisms are able to survive and proliferate in severe environmental conditions. The increasing number of complete sequences of prokaryotic genomes has provided the basis for studying the molecular mechanisms of their adaptation at the genomic level. We apply here a computer-based approach to compare the genomes and proteomes from <it>P. furiosus, P. horikoshii</it>, and <it>P. abyssi </it>to identify features of their molecular evolution related to adaptation strategy to diverse environmental conditions.</p> <p>Results</p> <p>Phylogenetic analysis of rRNA genes from 26 Pyrococcus strains suggested that the divergence of <it>P. furiosus, P. horikoshii </it>and <it>P. abyssi </it>might have occurred from ancestral deep-sea organisms. It was demonstrated that the function of genes that have been subject to positive Darwinian selection is closely related to abiotic and biotic conditions to which archaea managed to become adapted. Divergence of the <it>P. furiosus </it>archaea might have been due to loss of some genes involved in cell motility or signal transduction, and/or to evolution under positive selection of the genes for translation machinery. In the course of <it>P. horikoshii </it>divergence, positive selection was found to operate mainly on the transcription machinery; divergence of <it>P. abyssi </it>was related with positive selection for the genes mainly involved in inorganic ion transport. Analysis of radical amino acid replacement rate in evolving <it>P. furiosus, P. horikoshii </it>and <it>P. abyssi </it>showed that the fixation rate was higher for radical substitutions relative to the volume of amino acid side-chain.</p> <p>Conclusions</p> <p>The current results give due credit to the important role of hydrostatic pressure as a cause of variability in the <it>P. furiosus, P. horikoshii </it>and <it>P. abyssi </it>genomes evolving in different habitats. Nevertheless, adaptation to pressure does not appear to be the sole factor ensuring adaptation to environment. For example, at the stage of the divergence of <it>P. horikoshii </it>and <it>P. abyssi</it>, an essential evolutionary role may be assigned to changes in the trophic chain, namely, acquisition of a consumer status at a high (<it>P. horikoshii</it>) or low level (<it>P. abyssi</it>).</p

Human Genes Encoding Transcription Factors and Chromatin-Modifying Proteins Have Low Levels of Promoter Polymorphism: A Study of 1000 Genomes Project Data

The expression level of each gene is controlled by its regulatory regions, which determine the precise regulation in a tissue-specific manner, according to the developmental stage of the body and the necessity of a response to external stimuli. Nucleotide substitutions in regulatory gene regions may modify the affinity of transcription factors to their specific DNA binding sites, affecting the transcription rates of genes. In our previous research, we found that genes controlling the sensory perception of smell and genes involved in antigen processing and presentation were overrepresented significantly among genes with high SNP contents in their promoter regions. The goal of our study was to reveal functional features of human genes containing extremely small numbers of SNPs in promoter regions. Two functional groups were found to be overrepresented among genes whose promoters did not contain SNPs: (1) genes involved in gene-specific transcription and (2) genes controlling chromatin organization. We revealed that the 5′-regulatory regions of genes encoding transcription factors and chromatin-modifying proteins were characterized by reduced genetic variability. One important exception from this rule refers to genes encoding transcription factors with zinc-coordinating DNA-binding domains (DBDs), which underwent extensive expansion in vertebrates, particularly, in primate evolution. Hence, we obtained new evidence for evolutionary forces shaping variability in 5′-regulatory regions of genes

Recognition of interferon-inducible sites, promoters, and enhancers

BACKGROUND: Computational analysis of gene regulatory regions is important for prediction of functions of many uncharacterized genes. With this in mind, search of the target genes for interferon (IFN) induction appears of interest. IFNs are multi-functional cytokines. Their effects are immunomodulatory, antiviral, antibacterial, and antitumor. The interaction of the IFNs with their cell surface receptors produces an activation of several transcription factors. Four regulatory factors, ISGF3, STAT1, IRF1, and NF-κB, are essential for the function of the IFN system. The aim of this work is the development of computational approaches for the recognition of DNA binding sites for these factors and computer programs for the prediction of the IFN-inducible regions. RESULTS: We developed computational approaches to the recognition of the binding sites for ISGF3, STAT1, IRF1, and NF-κB. Analysis of the distribution of these binding sites demonstrated that the regions -500 upstream of the transcription start site in IFN-inducible genes are enriched in putative binding sites for these transcription factors. Based on selected combinations of the sites whose frequencies were significantly higher than in the other functional gene groups, we developed methods for the prediction of the IFN-inducible promoters and enhancers. We analyzed 1004 sequences of the IFN-inducible genes compiled using microarray data analyses and also about 10,000 human gene sequences from the EPD and RefSeq databases; 74 of 1,664 human genes annotated in EPD were significantly IFN-inducible. CONCLUSION: Analyses of several control datasets demonstrated that the developed methods have a high accuracy of prediction of the IFN-inducible genes. Application of these methods to several datasets suggested that the number of the IFN-inducible genes is approximately 1500–2000 in the human genome

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

BACKGROUND: Obesity is heritable. It predisposes to many diseases. The objectives of this study were to create a compendium of genes relevant to feeding behavior (FB) and/or body weight (BW) regulation; to construct and to analyze networks formed by associations between genes/proteins; and to identify the most significant genes, biological processes/pathways, and tissues/organs involved in BW regulation. RESULTS: The compendium of genes controlling FB or BW includes 578 human genes. Candidate genes were identified from various sources, including previously published original research and review articles, GWAS meta-analyses, and OMIM (Online Mendelian Inheritance in Man). All genes were ranked according to knowledge about their biological role in body weight regulation and classified according to expression patterns or functional characteristics. Substantial and overrepresented numbers of genes from the compendium encoded cell surface receptors, signaling molecules (hormones, neuropeptides, cytokines), transcription factors, signal transduction proteins, cilium and BBSome components, and lipid binding proteins or were present in the brain-specific list of tissue-enriched genes identified with TSEA tool. We identified 27 pathways from KEGG, REACTOME and BIOCARTA whose genes were overrepresented in the compendium. Networks formed by physical interactions or homological relationships between proteins or interactions between proteins involved in biochemical/signaling pathways were reconstructed and analyzed. Subnetworks and clusters identified by the MCODE tool included genes/proteins associated with cilium morphogenesis, signal transduction proteins (particularly, G protein-coupled receptors, kinases or proteins involved in response to insulin stimulus) and transcription regulation (particularly nuclear receptors). We ranked GWAS genes according to the number of neighbors in three networks and revealed 22 GWAS genes involved in the brain-specific PPI network. On the base of the most reliable PPIs functioning in the brain tissue, new regulatory schemes interpreting relevance to BW regulation are proposed for three GWAS genes (ETV5, LRP1B, and NDUFS3). CONCLUSIONS: A compendium comprising 578 human genes controlling FB or BW was designed, and the most significant functional groups of genes, biological processes/pathways, and tissues/organs involved in BW regulation were revealed. We ranked genes from the GWAS meta-analysis set according to the number and quality of associations in the networks and then according to their involvement in the brain-specific PPI network and proposed new regulatory schemes involving three GWAS genes (ETV5, LRP1B, and NDUFS3) in BW regulation. The compendium is expected to be useful for pathology risk estimation and for design of new pharmacological approaches in the treatment of human obesity

NPRD: Nucleosome Positioning Region Database

Nucleosome Positioning Region Database (NPRD), which is compiling the available experimental data on locations and characteristics of nucleosome formation sites (NFSs), is the first curated NFS-oriented database. The object of the database is a single NFS described in an individual entry. When annotating results of NFS experimental mapping, we pay special attention to several important functional characteristics, such as the relationship between type of gene activity and nucleosome positioning, the influence of non-histone proteins on nucleosome formation, type of the variant of nucleosome positioning (translational or rotational), indication of tissue types and states of cell activity, description of experimental methods used and accuracy of nucleosome position determination, and the results of applying theoretical and computer methods to the analysis of contextual and conformational DNA properties. At present, the NPRD database contains 438 entries and integrates the data described in 124 original papers. The database URL: http://srs6.bionet.nsc.ru/srs6/. Then click the button ‘Databank’ and open the link NUCLEOSOME

Fatma Aliye and Defense of Islamic Values

The article concerns an analysis of the recently published text by Fatma Aliye debating with European ideas and prejudices about Islam that has not been a subject of interest in the South Slavonic intellectual and academic circles. Fatma Aliye (1862–1936) was the first Turkish woman novelist, the first Turkish woman philosopher, and the author of the book Tezâhür-i Hakikat (Appearance of Truth) that was published for the first time in January 2016 on the occasion of the 80th anniversary of her death. Like some writers of the Tanzimat era, especially Namik Kemal, Fatma Aliye entered the debate with the European writers wishing to oppose the prevailing Orientalist approach in Europe that had been blaming Islam for the stagnation of sciences and culture. She demonstrated enviable erudition and devotion to the Islamic culture. Her views show the permanent duality of the Ottoman intellectuals between their desire for Westernization and their need to stay in the Islamic tradition. In many aspects, the approaches to Islam and the defence of Islamic values of Fatma Aliye are still current

Disruptive Selection of Human Immunostimulatory and Immunosuppressive Genes Both Provokes and Prevents Rheumatoid Arthritis, Respectively, as a Self-Domestication Syndrome

Using our previously published Web service SNP_TATA_Comparator, we conducted a genome-wide study of single-nucleotide polymorphisms (SNPs) within core promoters of 68 human rheumatoid arthritis (RA)-related genes. Using 603 SNPs within 25 genes clinically associated with RA-comorbid disorders, we predicted 84 and 70 candidate SNP markers for overexpression and underexpression of these genes, respectively, among which 58 and 96 candidate SNP markers, respectively, can relieve and worsen RA as if there is a neutral drift toward susceptibility to RA. Similarly, we predicted natural selection toward susceptibility to RA for 8 immunostimulatory genes (e.g., IL9R) and 10 genes most often associated with RA (e.g., NPY). On the contrary, using 25 immunosuppressive genes, we predicted 70 and 109 candidate SNP markers aggravating and relieving RA, respectively (e.g., IL1R2 and TGFB2), suggesting that natural selection can simultaneously additionally yield resistance to RA. We concluded that disruptive natural selection of human immunostimulatory and immunosuppressive genes is concurrently elevating and reducing the risk of RA, respectively. So, we hypothesize that RA in human could be a self-domestication syndrome referring to evolution patterns in domestic animals. We tested this hypothesis by means of public RNA-Seq data on 1740 differentially expressed genes (DEGs) of pets vs. wild animals (e.g., dogs vs. wolves). The number of DEGs in the domestic animals corresponding to worsened RA condition in humans was significantly larger than that in the related wild animals (10 vs. 3). Moreover, much less DEGs in the domestic animals were accordant to relieved RA condition in humans than those in the wild animals (1 vs. 8 genes). This indicates that the anthropogenic environment, in contrast to a natural one, affects gene expression across the whole genome (e.g., immunostimulatory and immunosuppressive genes) in a manner that likely contributes to RA. The difference in gene numbers is statistically significant as confirmed by binomial distribution (p &lt; 0.01), Pearson’s χ2 (p &lt; 0.01), and Fisher’s exact test (p &lt; 0.05). This allows us to propose RA as a candidate symptom within a self-domestication syndrome. Such syndrome might be considered as a human’s payment with health for the benefits received during evolution

Cancer Stem Cells: Emergent Nature of Tumor Emergency

A functional analysis of 167 genes overexpressed in Krebs-2 tumor initiating cells was performed. In the first part of the study, the genes were analyzed for their belonging to one or more of the three groups, which represent the three major phenotypic manifestation of malignancy of cancer cells, namely (1) proliferative self-sufficiency, (2) invasive growth and metastasis, and (3) multiple drug resistance. 96 genes out of 167 were identified as possible contributors to at least one of these fundamental properties. It was also found that substantial part of these genes are also known as genes responsible for formation and/or maintenance of the stemness of normal pluri-/multipotent stem cells. These results suggest that the malignancy is simply the ability to maintain the stem cell specific genes expression profile, and, as a consequence, the stemness itself regardless of the controlling effect of stem niches. In the second part of the study, three stress factors combined into the single concept of “generalized cellular stress,” which are assumed to activate the expression of these genes, were defined. In addition, possible mechanisms for such activation were identified. The data obtained suggest the existence of a mechanism for the de novo formation of a pluripotent/stem phenotype in the subpopulation of “committed” tumor cells