@article{8645, abstract = {Epistasis, the context-dependence of the contribution of an amino acid substitution to fitness, is common in evolution. To detect epistasis, fitness must be measured for at least four genotypes: the reference genotype, two different single mutants and a double mutant with both of the single mutations. For higher-order epistasis of the order n, fitness has to be measured for all 2n genotypes of an n-dimensional hypercube in genotype space forming a ‘combinatorially complete dataset’. So far, only a handful of such datasets have been produced by manual curation. Concurrently, random mutagenesis experiments have produced measurements of fitness and other phenotypes in a high-throughput manner, potentially containing a number of combinatorially complete datasets. We present an effective recursive algorithm for finding all hypercube structures in random mutagenesis experimental data. To test the algorithm, we applied it to the data from a recent HIS3 protein dataset and found all 199 847 053 unique combinatorially complete genotype combinations of dimensionality ranging from 2 to 12. The algorithm may be useful for researchers looking for higher-order epistasis in their high-throughput experimental data.}, author = {Esteban, Laura A and Lonishin, Lyubov R and Bobrovskiy, Daniil M and Leleytner, Gregory and Bogatyreva, Natalya S and Kondrashov, Fyodor and Ivankov, Dmitry N }, issn = {1460-2059}, journal = {Bioinformatics}, number = {6}, pages = {1960--1962}, publisher = {Oxford Academic}, title = {{HypercubeME: Two hundred million combinatorially complete datasets from a single experiment}}, doi = {10.1093/bioinformatics/btz841}, volume = {36}, year = {2020}, } @article{8700, abstract = {Translation termination is a finishing step of protein biosynthesis. The significant role in this process belongs not only to protein factors of translation termination but also to the nearest nucleotide environment of stop codons. There are numerous descriptions of stop codons readthrough, which is due to specific nucleotide sequences behind them. However, represented data are segmental and don’t explain the mechanism of the nucleotide context influence on translation termination. It is well known that stop codon UAA usage is preferential for A/T-rich genes, and UAG, UGA—for G/C-rich genes, which is related to an expression level of these genes. We investigated the connection between a frequency of nucleotides occurrence in 3' area of stop codons in the human genome and their influence on translation termination efficiency. We found that 3' context motif, which is cognate to the sequence of a stop codon, stimulates translation termination. At the same time, the nucleotide composition of 3' sequence that differs from stop codon, decreases translation termination efficiency.}, author = {Sokolova, E. E. and Vlasov, Petr and Egorova, T. V. and Shuvalov, A. V. and Alkalaeva, E. Z.}, issn = {16083245}, journal = {Molecular Biology}, number = {5}, pages = {739--748}, publisher = {Springer Nature}, title = {{The influence of A/G composition of 3' stop codon contexts on translation termination efficiency in eukaryotes}}, doi = {10.1134/S0026893320050088}, volume = {54}, year = {2020}, } @article{8701, abstract = {Translation termination is a finishing step of protein biosynthesis. The significant role in this process belongs not only to protein factors of translation termination but also to the nearest nucleotide environment of stop codons. There are numerous descriptions of stop codons readthrough, which is due to specific nucleotide sequences behind them. However, represented data are segmental and don’t explain the mechanism of the nucleotide context influence on translation termination. It is well known that stop codon UAA usage is preferential for A/T-rich genes, and UAG, UGA—for G/C-rich genes, which is related to an expression level of these genes. We investigated the connection between a frequency of nucleotides occurrence in 3' area of stop codons in the human genome and their influence on translation termination efficiency. We found that 3' context motif, which is cognate to the sequence of a stop codon, stimulates translation termination. At the same time, the nucleotide composition of 3' sequence that differs from stop codon, decreases translation termination efficiency.}, author = {Sokolova, E. E. and Vlasov, Petr and Egorova, T. V. and Shuvalov, A. V. and Alkalaeva, E. Z.}, issn = {00268984}, journal = {Molekuliarnaia biologiia}, number = {5}, pages = {837--848}, publisher = {Russian Academy of Sciences}, title = {{The influence of A/G composition of 3' stop codon contexts on translation termination efficiency in eukaryotes}}, doi = {10.31857/S0026898420050080}, volume = {54}, year = {2020}, } @article{8707, abstract = {Dynamic changes in the three-dimensional (3D) organization of chromatin are associated with central biological processes, such as transcription, replication and development. Therefore, the comprehensive identification and quantification of these changes is fundamental to understanding of evolutionary and regulatory mechanisms. Here, we present Comparison of Hi-C Experiments using Structural Similarity (CHESS), an algorithm for the comparison of chromatin contact maps and automatic differential feature extraction. We demonstrate the robustness of CHESS to experimental variability and showcase its biological applications on (1) interspecies comparisons of syntenic regions in human and mouse models; (2) intraspecies identification of conformational changes in Zelda-depleted Drosophila embryos; (3) patient-specific aberrant chromatin conformation in a diffuse large B-cell lymphoma sample; and (4) the systematic identification of chromatin contact differences in high-resolution Capture-C data. In summary, CHESS is a computationally efficient method for the comparison and classification of changes in chromatin contact data.}, author = { Galan, Silvia and Machnik, Nick N and Kruse, Kai and Díaz, Noelia and Marti-Renom, Marc A and Vaquerizas, Juan M}, issn = {15461718}, journal = {Nature Genetics}, pages = {1247--1255}, publisher = {Springer Nature}, title = {{CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction}}, doi = {10.1038/s41588-020-00712-y}, volume = {52}, year = {2020}, } @article{7603, abstract = {Plants are exposed to a variety of abiotic and biotic stresses that may result in DNA damage. Endogenous processes - such as DNA replication, DNA recombination, respiration, or photosynthesis - are also a threat to DNA integrity. It is therefore essential to understand the strategies plants have developed for DNA damage detection, signaling, and repair. Alternative splicing (AS) is a key post-transcriptional process with a role in regulation of gene expression. Recent studies demonstrate that the majority of intron-containing genes in plants are alternatively spliced, highlighting the importance of AS in plant development and stress response. Not only does AS ensure a versatile proteome and influence the abundance and availability of proteins greatly, it has also emerged as an important player in the DNA damage response (DDR) in animals. Despite extensive studies of DDR carried out in plants, its regulation at the level of AS has not been comprehensively addressed. Here, we provide some insights into the interplay between AS and DDR in plants.}, author = {Nimeth, Barbara Anna and Riegler, Stefan and Kalyna, Maria}, issn = {1664462X}, journal = {Frontiers in Plant Science}, publisher = {Frontiers}, title = {{Alternative splicing and DNA damage response in plants}}, doi = {10.3389/fpls.2020.00091}, volume = {11}, year = {2020}, } @article{7622, abstract = {The International Young Physicists' Tournament (IYPT) continued in 2018 in Beijing, China and 2019 in Warsaw, Poland with its 31st and 32nd editions. The IYPT is a modern scientific competition for teams of high school students, also known as the Physics World Cup. It involves long-term theoretical and experimental work focused on solving 17 publicly announced open-ended problems in teams of five. On top of that, teams have to present their solutions in front of other teams and a scientific jury, and get opposed and reviewed by their peers. Here we present a brief information about the competition with a specific focus on one of the IYPT 2018 tasks, the 'Ring Oiler'. This seemingly simple mechanical problem appeared to be of such a complexity that even the dozens of participating teams and jurying scientists were not able to solve all of its subtleties.}, author = {Plesch, Martin and Plesník, Samuel and Ruzickova, Natalia}, issn = {13616404}, journal = {European Journal of Physics}, number = {3}, publisher = {IOP Publishing}, title = {{The IYPT and the 'Ring Oiler' problem}}, doi = {10.1088/1361-6404/ab6414}, volume = {41}, year = {2020}, } @article{6898, abstract = {Background Chlamydia are ancient intracellular pathogens with reduced, though strikingly conserved genome. Despite their parasitic lifestyle and isolated intracellular environment, these bacteria managed to avoid accumulation of deleterious mutations leading to subsequent genome degradation characteristic for many parasitic bacteria. Results We report pan-genomic analysis of sixteen species from genus Chlamydia including identification and functional annotation of orthologous genes, and characterization of gene gains, losses, and rearrangements. We demonstrate the overall genome stability of these bacteria as indicated by a large fraction of common genes with conserved genomic locations. On the other hand, extreme evolvability is confined to several paralogous gene families such as polymorphic membrane proteins and phospholipase D, and likely is caused by the pressure from the host immune system. Conclusions This combination of a large, conserved core genome and a small, evolvable periphery likely reflect the balance between the selective pressure towards genome reduction and the need to adapt to escape from the host immunity.}, author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.}, issn = {14712164}, journal = {BMC Genomics}, number = {1}, publisher = {BioMed Central}, title = {{Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}}, doi = {10.1186/s12864-019-6059-5}, volume = {20}, year = {2019}, } @article{7181, abstract = {Multiple sequence alignments (MSAs) are used for structural1,2 and evolutionary predictions1,2, but the complexity of aligning large datasets requires the use of approximate solutions3, including the progressive algorithm4. Progressive MSA methods start by aligning the most similar sequences and subsequently incorporate the remaining sequences, from leaf-to-root, based on a guide-tree. Their accuracy declines substantially as the number of sequences is scaled up5. We introduce a regressive algorithm that enables MSA of up to 1.4 million sequences on a standard workstation and substantially improves accuracy on datasets larger than 10,000 sequences. Our regressive algorithm works the other way around to the progressive algorithm and begins by aligning the most dissimilar sequences. It uses an efficient divide-and-conquer strategy to run third-party alignment methods in linear time, regardless of their original complexity. Our approach will enable analyses of extremely large genomic datasets such as the recently announced Earth BioGenome Project, which comprises 1.5 million eukaryotic genomes6.}, author = {Garriga, Edgar and Di Tommaso, Paolo and Magis, Cedrik and Erb, Ionas and Mansouri, Leila and Baltzis, Athanasios and Laayouni, Hafid and Kondrashov, Fyodor and Floden, Evan and Notredame, Cedric}, issn = {15461696}, journal = {Nature Biotechnology}, number = {12}, pages = {1466--1470}, publisher = {Springer Nature}, title = {{Large multiple sequence alignments with a root-to-leaf regressive method}}, doi = {10.1038/s41587-019-0333-6}, volume = {37}, year = {2019}, } @article{6419, abstract = {Characterizing the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here we determined the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. Just 15% of amino acids found in yeast His3 orthologues were always neutral while the impact on fitness of the remaining 85% depended on the genetic background. Furthermore, at 67% of sites, amino acid replacements were under sign epistasis, having both strongly positive and negative effect in different genetic backgrounds. 46% of sites were under reciprocal sign epistasis. The fitness impact of amino acid replacements was influenced by only a few genetic backgrounds but involved interaction of multiple sites, shaping a rugged fitness landscape in which many of the shortest paths between highly fit genotypes are inaccessible.}, author = {Pokusaeva, Victoria and Usmanova, Dinara R. and Putintseva, Ekaterina V. and Espinar, Lorena and Sarkisyan, Karen and Mishin, Alexander S. and Bogatyreva, Natalya S. and Ivankov, Dmitry and Akopyan, Arseniy and Avvakumov, Sergey and Povolotskaya, Inna S. and Filion, Guillaume J. and Carey, Lucas B. and Kondrashov, Fyodor}, issn = {15537404}, journal = {PLoS Genetics}, number = {4}, publisher = {Public Library of Science}, title = {{An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape}}, doi = {10.1371/journal.pgen.1008079}, volume = {15}, year = {2019}, } @article{6506, abstract = {How does environmental complexity affect the evolution of single genes? Here, we measured the effects of a set of Bacillus subtilis glutamate dehydrogenase mutants across 19 different environments—from phenotypically homogeneous single-cell populations in liquid media to heterogeneous biofilms, plant roots and soil populations. The effects of individual gene mutations on organismal fitness were highly reproducible in liquid cultures. However, 84% of the tested alleles showed opposing fitness effects under different growth conditions (sign environmental pleiotropy). In colony biofilms and soil samples, different alleles dominated in parallel replica experiments. Accordingly, we found that in these heterogeneous cell populations the fate of mutations was dictated by a combination of selection and drift. The latter relates to programmed prophage excisions that occurred during biofilm development. Overall, for each condition, a wide range of glutamate dehydrogenase mutations persisted and sometimes fixated as a result of the combined action of selection, pleiotropy and chance. However, over longer periods and in multiple environments, nearly all of this diversity would be lost—across all the environments and conditions that we tested, the wild type was the fittest allele.}, author = {Noda-García, Lianet and Davidi, Dan and Korenblum, Elisa and Elazar, Assaf and Putintseva, Ekaterina and Aharoni, Asaph and Tawfik, Dan S.}, issn = {2058-5276}, journal = {Nature Microbiology}, number = {7}, pages = {1221–1230}, publisher = {Springer Nature}, title = {{Chance and pleiotropy dominate genetic diversity in complex bacterial environments}}, doi = {10.1038/s41564-019-0412-y}, volume = {4}, year = {2019}, } @misc{9731, abstract = {OGs with putative pseudogenes by the number of affected genomes in different chlamydial species. Frameshift and nonsense mutations located less than 60 bp upstreamof the gene end or present in a single genome from the corresponding OG were excluded. (CSV 31 kb)}, author = {Sigalova, Olga and Chaplin, Andrei and Bochkareva, Olga and Shelyakin, Pavel and Filaretov, Vsevolod and Akkuratov, Evgeny and Burskaia, Valentina and Gelfand, Mikhail S.}, publisher = {Springer Nature}, title = {{Additional file 11 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}}, doi = {10.6084/m9.figshare.9808772.v1}, year = {2019}, } @misc{9783, abstract = {Predicted frameshift and nonsense mutations in Chlamydial pan-genome. For the analysis of putative pseudogenes, events located less than 60 bp. away from gene end or present in a single genome from the corresponding OG were excluded. (CSV 600 kb)}, author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.}, publisher = {Springer Nature}, title = {{Additional file 10 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}}, doi = {10.6084/m9.figshare.9808760.v1}, year = {2019}, } @misc{9789, author = {Pokusaeva, Victoria and Usmanova, Dinara R. and Putintseva, Ekaterina V. and Espinar, Lorena and Sarkisyan, Karen and Mishin, Alexander S. and Bogatyreva, Natalya S. and Ivankov, Dmitry and Akopyan, Arseniy and Avvakumov, Sergey and Povolotskaya, Inna S. and Filion, Guillaume J. and Carey, Lucas B. and Kondrashov, Fyodor}, publisher = {Public Library of Science}, title = {{Multiple alignment of His3 orthologues}}, doi = {10.1371/journal.pgen.1008079.s010}, year = {2019}, } @misc{9790, author = {Pokusaeva, Victoria and Usmanova, Dinara R. and Putintseva, Ekaterina V. and Espinar, Lorena and Sarkisyan, Karen and Mishin, Alexander S. and Bogatyreva, Natalya S. and Ivankov, Dmitry and Akopyan, Arseniy and Avvakumov, Sergey and Povolotskaya, Inna S. and Filion, Guillaume J. and Carey, Lucas B. and Kondrashov, Fyodor}, publisher = {Public Library of Science}, title = {{A statistical summary of segment libraries and sequencing results}}, doi = {10.1371/journal.pgen.1008079.s011}, year = {2019}, } @misc{9797, author = {Pokusaeva, Victoria and Usmanova, Dinara R. and Putintseva, Ekaterina V. and Espinar, Lorena and Sarkisyan, Karen and Mishin, Alexander S. and Bogatyreva, Natalya S. and Ivankov, Dmitry and Akopyan, Arseniy and Povolotskaya, Inna S. and Filion, Guillaume J. and Carey, Lucas B. and Kondrashov, Fyodor}, publisher = {Public Library of Science}, title = {{A statistical summary of segment libraries and sequencing results}}, doi = {10.1371/journal.pgen.1008079.s011}, year = {2019}, } @misc{9890, abstract = {Distribution of OGs with mosaic phyletic patterns across species (complete genomes only). (CSV 7 kb)}, author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.}, publisher = {Springer Nature}, title = {{Additional file 15 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}}, doi = {10.6084/m9.figshare.9808802.v1}, year = {2019}, } @misc{9892, abstract = {Distribution of OGs with mosaic phyletic patterns across species (all genomes). (CSV 10 kb)}, author = {Sigalova, Olga M. and Chaplin, Andrei V and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.}, publisher = {Springer Nature}, title = {{Additional file 16 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}}, doi = {10.6084/m9.figshare.9808814.v1}, year = {2019}, } @misc{9893, abstract = {Summary of peripheral genesa phyletic patterns and tree concordance. (CSV 26 kb)}, author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.}, publisher = {Springer Nature}, title = {{Additional file 17 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}}, doi = {10.6084/m9.figshare.9808820.v1}, year = {2019}, } @misc{9894, abstract = {Orthologous families (OFs) derived by MCL clustering of OGs. (CSV 189 kb)}, author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.}, publisher = {Springer Nature}, title = {{Additional file 18 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}}, doi = {10.6084/m9.figshare.9808826.v1}, year = {2019}, } @misc{9895, abstract = {Additional information on proteins from OG1. (CSV 30 kb)}, author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.}, publisher = {Springer Nature}, title = {{Additional file 19 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}}, doi = {10.6084/m9.figshare.9808835.v1}, year = {2019}, }