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A novel algorithm and original software were used to cluster all proteins encoded in plastids of 72 species of the rhodophytic branch. The results are publicly available at http://lab6.iitp.ru/ppc/redline72/ in a database that allows fast identification of clusters (protein families) both by a fragment of an amino acid sequence and by a phylogenetic profile of a protein. No such integral clustering with the corresponding functions can be found in the public domain. The putative regulons of the transcription factors Ycf28 and Ycf29 encoded in the plastids were identified using the clustering and the database. A regulation of translation initiation was proposed for the ycf24 gene in plastids of certain red algae and apicomplexans as well as a regulation of a putative gene in apicoplasts of Babesia spp. and Theileria parva. The conserved regulation of the ycf24 gene expression and specificity alternation of the transcription factor Ycf28 were shown in the plastids. A phylogenetic tree of plastids was generated for the rhodophytic branch. The hypothesis of the origin of apicoplasts from the common ancestor of all apicomplexans from plastids of red algae was confirmed. [ABSTRACT FROM AUTHOR]

A generic extension $${\mathbf{L}[x]}$$ by a real x is defined, in which the $${\mathsf{E}_0}$$ -class of x is a lightface $${{\it \Pi}^1_2}$$ (hence, ordinal-definable) set containing no ordinal-definable reals. [ABSTRACT FROM AUTHOR]

Background: Modeling of a complex biological process can explain the results of experimental studies and help predict its characteristics. Among such processes is transcription in the presence of competing RNA polymerases. This process involves RNA polymerases collision followed by transcription termination. Results: A mathematical and computer simulation model is developed to describe the competition of RNA polymerases during genes transcription on complementary DNA strands. E.g., in the barley Hordeum vulgare the polymerase competition occurs in the locus containing plastome genes psbA, rpl23, rpl2 and four bacterial type promoters. In heat shock experiments on isolated chloroplasts, a twofold decrease of psbA transcripts and even larger increase of rpl23-rpl2 transcripts were observed, which is well reproduced in the model. The model predictions are in good agreement with virtually all relevant experimental data (knockout, heat shock, chromatogram data, etc.). The model allows to hypothesize a mechanism of cell response to knockout and heat shock, as well as a mechanism of gene expression regulation in presence of RNA polymerase competition. The model is implemented for multiprocessor platforms with MPI and supported on Linux and MS Windows. The source code written in C++ is available under the GNU General Public License from the laboratory website. A userfriendly GUI version is also provided at http://lab6.iitp.ru/en/rivals. Conclusions: The developed model is in good agreement with virtually all relevant experimental data. The model can be applied to estimate intensities of binding of the holoenzyme and phage type RNA polymerase to their promoters using data on gene transcription levels, as well as to predict characteristics of RNA polymerases and the transcription process that are difficult to measure directly, e.g., the intensity (frequency) of holoenzyme binding to the promoter in correlation to its nucleotide composition and the type of σ-subunit, the amount of transcription initiation aborts, etc. The model can be used to make functional predictions, e.g., heat shock response in isolated chloroplasts and changes of gene transcription levels under knockout of different σ-subunits or RNA polymerases or due to gene expression regulation. Reviewers: This article was reviewed by Dr. Anthony Almudevar, Dr. Aniko Szabo, Dr. Yuri Wolf (nominated by Dr. Peter Olofsson) and Prof. Marek Kimmel. [ABSTRACT FROM AUTHOR]

RNAmodel web server was recently established at the IITP RAS to implement our previously proposed model of the classic attenuation regulation of gene expression in bacteria. This new model is based on the concept of resonant-like interaction between RNA polymerase and hairpins of RNA secondary structure formed during transcription. Our modeling relies on standard Monte Carlo procedures and covers all essential stages of the process, including initiation and elongation of transcription and translation; the deceleration of ribosome on regulatory codons, which depends on the concentration of charged amino acyl-tRNA; the polymerase shifting delay caused by secondary structure folded into the mRNA segment between ribosome and polymerase; and, ultimately, either transcription terminating prematurely or polymerase reaching a region of structural genes (antitermination). By means of Monte Carlo simulation we build a function p(c) which expresses the probability of termination (i.e., an enzyme activity) vs. the concentration of charged amino acyl-tRNA or of amino acid itself, measured in actual or relative units. [ABSTRACT FROM AUTHOR]

A new approach for comparative analysis of multiple trees reconstructed for representative protein families is proposed. This approach is based on the hypothesis of gene duplication, gene loss and horizontal gene transfer and makes use of stochastic methods and optimization. We present a species tree of 40 prokaryotic organisms obtained by our algorithm on the basis of 132 clusters of orthologous groups of proteins (COGs) from the GenBank of the National Center for Biotechnology Information (USA). We also present a computer technology intended to determine horizontally transferred genes. Some application results of the technology, based on comparative analysis of protein and species trees, are given. [ABSTRACT FROM AUTHOR]

We describe an algorithm (IRSA) for identification of common regulatory signals in samples of unaligned DNA sequences. The algorithm was tested on randomly generated sequences of fixed length with implanted signal of length 15 with 4 mutations, and on natural upstream regions of bacterial genes regulated by PurR, ArgR and CRP. Then it was applied to upstream regions of orthologous genes from Escherichia coli and related genomes. Some new palindromic binding and direct repeats signals were identified. Finally we present a parallel version suitable for computers supporting the MPI protocol. This implementation is not strictly bounded by the number of available processors. The computation speed linearly depends on the number of processors. [ABSTRACT FROM AUTHOR]

Aim: To confirm algorithm of determination of risk groups with physiological imbalance in the population exposed to unfavorable anthropogenic influences. Methods: The testing included such functional systems as constitution, myocardial contractility, autonomic regulation of the heart rate, regulation of peripheral circulation, psychomotor regulation, respiratory regulation and metabolism. Monitoring is carried out using computerized measurement instrumentation and data processing systems. Results: A risk group with pronounced shifts in the physiological balance was identified, which made up 38% of the surveyed population. The greatest contribution to the imbalance was made by the psychomotor system. Conclusion: We analyzed two different components of organism's adaptation: resistance and resilience. Physiological systems experiencing increasing load attain a tipping points, where even a weak disturbing influence can induce transition to a qualitatively different state. This transition can result in either recovery of the regulatory stability of the system, or its transition to a lower level (dysregulation) with further development of a pathology. In this regard, of paramount importance is early detection of the signals about approaching the tipping points, one of these is the slowing down phenomenon during functional tests. In view of intricate interaction of physiological systems, recording of as much indicators as possible is advisable. The method of partial correlations is effective for evaluation of adaptive interaction of systems. [ABSTRACT FROM AUTHOR]

In this paper, we prove the following. If n ≥ 3 , then there is a generic extension of L , the constructible universe, in which it is true that the set P (ω) ∩ L of all constructible reals (here—subsets of ω) is equal to the set P (ω) ∩ Δ n 1 of all (lightface) Δ n 1 reals. The result was announced long ago by Leo Harrington, but its proof has never been published. Our methods are based on almost-disjoint forcing. To obtain a generic extension as required, we make use of a forcing notion of the form Q = C ℂ × ∏ ν Q ν in L , where C adds a generic collapse surjection b from ω onto P (ω) ∩ L , whereas each Q ν , ν < ω 2 L , is an almost-disjoint forcing notion in the ω 1 -version, that adjoins a subset S ν of ω 1 L . The forcing notions involved are independent in the sense that no Q ν -generic object can be added by the product of C and all Q ξ , ξ ≠ ν . This allows the definition of each constructible real by a Σ n 1 formula in a suitably constructed subextension of the Q -generic extension. The subextension is generated by the surjection b, sets S ω · k + j with j ∈ b (k) , and sets S ξ with ξ ≥ ω · ω . A special character of the construction of forcing notions Q ν is L , which depends on a given n ≥ 3 , obscures things with definability in the subextension enough for vice versa any Δ n 1 real to be constructible; here the method of hidden invariance is applied. A discussion of possible further applications is added in the conclusive section. [ABSTRACT FROM AUTHOR]

Background: It is generally accepted that most evolutionary transformations at the phenotype level are associated either with rearrangements of genomic regulatory elements, which control the activity of gene networks, or with changes in the amino acid contents of proteins. Recently, evidence has accumulated that significant evolutionary transformations could also be associated with the loss/emergence of whole genes. The targeted identification of such genes is a challenging problem for both bioinformatics and evo-devo research., Results: To solve this problem we propose the WINEGRET method, named after the first letters of the title. Its main idea is to search for genes that satisfy two requirements: first, the desired genes were lost/emerged at the same evolutionary stage at which the phenotypic trait of interest was lost/emerged, and second, the expression of these genes changes significantly during the development of the trait of interest in the model organism. To verify the first requirement, we do not use existing databases of orthologs, but rely purely on gene homology and local synteny by using some novel quickly computable conditions. Genes satisfying the second requirement are found by deep RNA sequencing. As a proof of principle, we used our method to find genes absent in extant amniotes (reptiles, birds, mammals) but present in anamniotes (fish and amphibians), in which these genes are involved in the regeneration of large body appendages. As a result, 57 genes were identified. For three of them, c-c motif chemokine 4, eotaxin-like, and a previously unknown gene called here sod4, essential roles for tail regeneration were demonstrated. Noteworthy, we established that the latter gene belongs to a novel family of Cu/Zn-superoxide dismutases lost by amniotes, SOD4., Conclusions: We present a method for targeted identification of genes whose loss/emergence in evolution could be associated with the loss/emergence of a phenotypic trait of interest. In a proof-of-principle study, we identified genes absent in amniotes that participate in body appendage regeneration in anamniotes. Our method provides a wide range of opportunities for studying the relationship between the loss/emergence of phenotypic traits and the loss/emergence of specific genes in evolution., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient are as genetically diverse as those from different patients, while within-tumor genetic heterogeneity is significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there is no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)