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Mikhail S. Gelfand - One of the best experts on this subject based on the ideXlab platform.
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Evolution of the Exon-Intron Structure in Ciliate Genomes.
PloS one, 2016Co-Authors: Vladyslav S. Bondarenko, Mikhail S. GelfandAbstract:A typical eukaryotic gene is comprised of alternating stretches of regions, exons and Introns, retained in and spliced out a mature mRNA, respectively. Although the length of Introns may vary substantially among organisms, a large fraction of genes contains short Introns in many species. Notably, some Ciliates (Paramecium and Nyctotherus) possess only ultra-short Introns, around 25 bp long. In Paramecium, ultra-short Introns with length divisible by three (3n) are under strong evolutionary pressure and have a high frequency of in-frame stop codons, which, in the case of Intron retention, cause premature termination of mRNA translation and consequent degradation of the mis-spliced mRNA by the nonsense-mediated decay mechanism. Here, we analyzed Introns in five genera of Ciliates, Paramecium, Tetrahymena, Ichthyophthirius, Oxytricha, and Stylonychia. Introns can be classified into two length classes in Tetrahymena and Ichthyophthirius (with means 48 bp, 69 bp, and 55 bp, 64 bp, respectively), but, surprisingly, comprise three distinct length classes in Oxytricha and Stylonychia (with means 33-35 bp, 47-51 bp, and 78-80 bp). In most ranges of the Intron lengths, 3n Introns are underrepresented and have a high frequency of in-frame stop codons in all studied species. Introns of Paramecium, Tetrahymena, and Ichthyophthirius are preferentially located at the 5' and 3' ends of genes, whereas Introns of Oxytricha and Stylonychia are strongly skewed towards the 5' end. Analysis of evolutionary conservation shows that, in each studied genome, a significant fraction of Intron positions is conserved between the orthologs, but Intron lengths are not correlated between the species. In summary, our study provides a detailed characterization of Introns in several genera of Ciliates and highlights some of their distinctive properties, which, together, indicate that splicing spellchecking is a universal and evolutionarily conserved process in the biogenesis of short Introns in various representatives of Ciliates.
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evolution of exon Intron Structure and alternative splicing in fruit flies and malarial mosquito genomes
Genome Research, 2006Co-Authors: Dmitry B. Malko, Andrey A. Mironov, Vsevolod J. Makeev, Mikhail S. GelfandAbstract:Comparative analysis of alternative splicing of orthologous genes from fruit flies (Drosophila melanogaster and Drosophila pseudoobscura) and mosquito (Anopheles gambiae) demonstrated that both in the fruit fly genes and in fruit fly–mosquito comparisons, constitutive exons and splicing sites are more conserved than alternative ones. While >97% of constitutive D. melanogaster exons are conserved in D. pseudoobscura, only ∼80% of alternative exons are conserved. Similarly, 77% of constitutive fruit fly exons are conserved in the mosquito genes, compared with <50% of alternative exons. Internal alternatives are more conserved than terminal ones. Retained Introns are the least conserved, alternative acceptor sites are slightly more conserved than donor sites, and mutually exclusive exons are almost as conserved as constitutive exons. Cassette and mutually exclusive exons experience almost no Intron insertions. We also observed cases of interconversion of various elementary alternatives, e.g., transformation of cassette exons into alternative sites. These results agree with the observations made earlier in human–mouse comparisons and demonstrate that the phenomenon of relatively low conservation of alternatively spliced regions may be universal, as it has been observed in different taxonomic groups (mammals and insects) and at various evolutionary distances.
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Evolution of exon–Intron Structure and alternative splicing in fruit flies and malarial mosquito genomes
Genome research, 2006Co-Authors: Dmitry B. Malko, Andrey A. Mironov, Vsevolod J. Makeev, Mikhail S. GelfandAbstract:Comparative analysis of alternative splicing of orthologous genes from fruit flies (Drosophila melanogaster and Drosophila pseudoobscura) and mosquito (Anopheles gambiae) demonstrated that both in the fruit fly genes and in fruit fly–mosquito comparisons, constitutive exons and splicing sites are more conserved than alternative ones. While >97% of constitutive D. melanogaster exons are conserved in D. pseudoobscura, only ∼80% of alternative exons are conserved. Similarly, 77% of constitutive fruit fly exons are conserved in the mosquito genes, compared with
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Evolution of the exon-Intron Structure and alternative splicing of the MAGE-A family of cancer/testis antigens
Journal of molecular evolution, 2004Co-Authors: Irena I. Artamonova, Mikhail S. GelfandAbstract:Cancer/testis antigens (CT-antigens) are proteins that are predominantly expressed in cancer and testis and thus are possible targets for immunotherapy. Most of them form large multigene families. The evolution of the MAGE-A family of CT-antigens is characterized by four processes: (1) gene duplications; (2) duplications of the initial exon; (3) point mutations and short insertions/deletions inactivating splicing sites or creating new sites; and (4) deletions removing sites and creating chimeric exons. All this concerns the genomic regions upstream of the coding region, creating a wide diversity of isoforms with different 5′-untranslated regions. Many of these isoforms are gene-specific and have emerged due to point mutations in alternative and constitutive splicing sites. There are also examples of chimeric mRNAs, likely produced by splicing of read-through transcripts. Since there is consistent use of homologous sites for different genes and no random, indiscriminant use of preexisting cryptic sites, it is likely that most observed isoforms are functional, and do not result from relaxed control in transformed cells.
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Prediction of the exon-Intron Structure by comparison of genomic sequences
Molecular Biology, 2000Co-Authors: Pavel S. Novichkov, Mikhail S. Gelfand, Andrey A. MironovAbstract:An algorithm for prediction of the exon-Intron Structure of higher eukaryotic genes is suggested. The algorithm is based on comparison of genomic sequences of homologous genes from different species. It uses the fact that protein-coding sequences evolve slower than noncoding regions. Unlike the existing comparison methods, the proposed algorithm, which is a modified version of splicing alignment, compares not nucleotide but amino acid sequences, which increases its sensitivity. Conservation of the exon-Intron Structures of the compared genes is not assumed. The algorithm is implemented in the program Pro-Gen. The testing of the algorithm demonstrated that it can be successfully applied to prediction of vertebrate genes, and in some cases, for more distant comparisons (e.g., vertebrates and insects or nematodes). Thus, the program can be used for prediction of human genes by comparison with genes of model organisms: mouse, fugu, drosophila, and nematode. The algorithm overcomes deficiencies of the existing methods, both statistical (insufficient reliability) and similarity-based (inapplicability to completely new genes).
Ekaterina Chesnokova - One of the best experts on this subject based on the ideXlab platform.
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A Long Short-Term Memory Neural Network Used to Predict the Exon–Intron Structure of a Gene
Biophysics, 2020Co-Authors: L. A. Uroshlev, N. V. Bal, Ekaterina ChesnokovaAbstract:Several models of long short-term memory (LSTM) neural networks were constructed. Each model was trained on the complete mouse genome to predict the exon–Intron Structure of a gene. The performance of the neural networks was compared using a test sample and experimental sequencing data obtained using rat brain cell cultures after treatment with spicing inhibitors.
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a long short term memory neural network used to predict the exon Intron Structure of a gene
Biophysics, 2020Co-Authors: L. A. Uroshlev, N. V. Bal, Ekaterina ChesnokovaAbstract:Several models of long short-term memory (LSTM) neural networks were constructed. Each model was trained on the complete mouse genome to predict the exon–Intron Structure of a gene. The performance of the neural networks was compared using a test sample and experimental sequencing data obtained using rat brain cell cultures after treatment with spicing inhibitors.
Jc Prudhomme - One of the best experts on this subject based on the ideXlab platform.
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Structure and organization of the Bombyx mori sericin 1 gene and of the sericins 1 deduced from the sequence of the Ser 1B cDNA.
Insect Biochemistry and Molecular Biology, 1997Co-Authors: A. Garel, G. Deleage, Jc PrudhommeAbstract:The sericin 1 primary transcript of the silkworm Bombyx mori is differentially spliced via a tissue- and developmentally-regulated process. From a middle silk gland cDNA library, we have elucidated the sequence of one of the four mRNAs, the 4.0 kb Ser1B mRNA. Determination of alternative or constitutive exons and Intron-exon boundaries allowed us to establish the nine exon-eight Intron Structure of the Ser1 gene. From these and previous data, it was possible to deduce the sequence of the sericins 1 and to predict the secondary Structure and physiochemical properties of the different regions of the proteins.
Francis Galibert - One of the best experts on this subject based on the ideXlab platform.
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Genomic organization of the extracellular coding region of the human FGFR4 and FLT4 genes: evolution of the genes encoding receptor tyrosine kinases with immunoglobulin-like domains.
Journal of molecular evolution, 1997Co-Authors: François Agnès, Catherine André, Marguerite-marie Toux, Francis GalibertAbstract:Receptor tyrosine kinases with five, seven, and three Ig-like domains in their extracellular region are grouped in subclasses IIIa, IIIb, and IIIc, respectively. Here, we describe the genomic organization of the extracellular coding region of the human FGFR4 (IIIc) and FLT4 (IIIb) genes and compare it to that of the human FGFR1(IIIc), KIT, and FMS (IIIa). The results show that while genes belonging to the same subclass have an identical exon/Intron Structure in their extracellular coding region-as they do in their intracellular coding regiongenes of related subclasses only have a similar exon/ Intron Structure. These results strongly support the hypothesis that the genes of the three subclasses evolved from a common ancestor by duplications involving entire genes, already in pieces. Hypotheses on the origin of Introns and on the difference in the number of extracellular Ig-like domains in the three gene subclasses are discussed.
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Molecular evolution of the genes encoding receptor tyrosine kinase with immunoglobulinlike domains
Journal of molecular evolution, 1995Co-Authors: Dominique Rousset, François Agnès, Philippe Lachaume, Catherine André, Francis GalibertAbstract:Receptor tyrosine kinases (RTK) with five, three, or seven immunoglobulinlike domains in their extracellular regions are classified as subclasses III, IV, and V, respectively. Conservation of the exon/Intron Structure of the downstream part of the human KIT, FMS, and FLT3 genes that encode RTK of subclass III together with the particular chromosomal localization of these genes suggests that RTKIII genes have evolved from a common ancestor by cis and trans duplications. To strengthen this model of evolution and to determine if it can be extended to RTKIV and V genes, we constructed a phylogenetic tree of RTKIII, IV, and V on the basis of a multiple alignment of their catalytic tyrosine kinase domain sequences and determined the exon/Intron Structure of PDGFRA (subclass III), FGFR4 (subclass IV), and FLT4 (subclass V) genes in their downstream part. Phylogenetic analyses with amino acid or nucleotide sequences both resulted in one most parsimonious tree. The phylogenetic trees obtained indicate that all three subclasses are well individuated and that RTKIII and RTKV are closer to each other than RTKIV. Furthermore, RTKIII and FLT4 (subclass V) genes possess the same exon/Intron Structure in their downstream part while the Structure of the RTKIV genes is very similar to that of RTKIII and FLT4. Both approaches are in complete agreement and indicate that RTKIII, IV, and V genes most probably evolved from a common ancestor already “in pieces” by successive duplications involving entire genes.
Vladimir A Ivanisenko - One of the best experts on this subject based on the ideXlab platform.
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Computer analysis of protein functional sites projection on exon Structure of genes in Metazoa
BMC Genomics, 2015Co-Authors: Irina V Medvedeva, Pavel S Demenkov, Vladimir A IvanisenkoAbstract:Background Study of the relationship between the structural and functional organization of proteins and their coding genes is necessary for an understanding of the evolution of molecular systems and can provide new knowledge for many applications for designing proteins with improved medical and biological properties. It is well known that the functional properties of proteins are determined by their functional sites. Functional sites are usually represented by a small number of amino acid residues that are distantly located from each other in the amino acid sequence. They are highly conserved within their functional group and vary significantly in Structure between such groups. According to this facts analysis of the general properties of the structural organization of the functional sites at the protein level and, at the level of exon-Intron Structure of the coding gene is still an actual problem. Results One approach to this analysis is the projection of amino acid residue positions of the functional sites along with the exon boundaries to the gene Structure. In this paper, we examined the discontinuity of the functional sites in the exon-Intron Structure of genes and the distribution of lengths and phases of the functional site encoding exons in vertebrate genes. We have shown that the DNA fragments coding the functional sites were in the same exons, or in close exons. The observed tendency to cluster the exons that code functional sites which could be considered as the unit of protein evolution. We studied the characteristics of the Structure of the exon boundaries that code, and do not code, functional sites in 11 Metazoa species. This is accompanied by a reduced frequency of intercodon gaps (phase 0) in exons encoding the amino acid residue functional site, which may be evidence of the existence of evolutionary limitations to the exon shuffling. Conclusions These results characterize the features of the coding exon-Intron Structure that affect the functionality of the encoded protein and allow a better understanding of the emergence of biological diversity.
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Computer analysis of protein functional sites projection on exon Structure of genes in Metazoa.
BMC genomics, 2015Co-Authors: Irina V Medvedeva, Pavel S Demenkov, Vladimir A IvanisenkoAbstract:Study of the relationship between the structural and functional organization of proteins and their coding genes is necessary for an understanding of the evolution of molecular systems and can provide new knowledge for many applications for designing proteins with improved medical and biological properties. It is well known that the functional properties of proteins are determined by their functional sites. Functional sites are usually represented by a small number of amino acid residues that are distantly located from each other in the amino acid sequence. They are highly conserved within their functional group and vary significantly in Structure between such groups. According to this facts analysis of the general properties of the structural organization of the functional sites at the protein level and, at the level of exon-Intron Structure of the coding gene is still an actual problem. One approach to this analysis is the projection of amino acid residue positions of the functional sites along with the exon boundaries to the gene Structure. In this paper, we examined the discontinuity of the functional sites in the exon-Intron Structure of genes and the distribution of lengths and phases of the functional site encoding exons in vertebrate genes. We have shown that the DNA fragments coding the functional sites were in the same exons, or in close exons. The observed tendency to cluster the exons that code functional sites which could be considered as the unit of protein evolution. We studied the characteristics of the Structure of the exon boundaries that code, and do not code, functional sites in 11 Metazoa species. This is accompanied by a reduced frequency of intercodon gaps (phase 0) in exons encoding the amino acid residue functional site, which may be evidence of the existence of evolutionary limitations to the exon shuffling. These results characterize the features of the coding exon-Intron Structure that affect the functionality of the encoded protein and allow a better understanding of the emergence of biological diversity.
