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Biomedical subjects

V V Kapitonov

Publications and source records attributed to V V Kapitonov.

At least 19 recordsLinked to original sources

Clustering, duplication and chromosomal distribution of mouse SINE retrotransposons.

We analyzed potential mechanisms determining chromosomal distributions of the mouse B1 and B2 non-LTR retrotransposons, also known as SINE elements. We report that young B1 and B2 SINEs are underrepresented on chromosome X relative to autosomes, which is consistent with their integration in male germ lines. As the age of the SINE elements progresses, their densities on chromosome X increase relative to autosomal densities, possibly due to differences in ectopic recombination rates between chromosome X and autosomes. Furthermore, unlike young human Alus that tend to be integrated outside Alu-dense regions, young B1 and B2 elements are found mostly in SINE-rich clusters. The B1- or B2-rich clusters are more likely to contain duplicated elements than B1- or B2-poor chromosomal regions. We also present evidence indicating potential association of B1 and B2 elements with intra-chromosomal segmental duplications. No such association was found with inter-chromosomal duplications. We propose that the accumulation of mouse SINE elements observed in GC-rich regions may be due to the excess of DNA duplications over deletions in gene-rich regions that tend to be GC rich.

Animals↗

Repbase Update, a database of eukaryotic repetitive elements.

Repbase Update is a comprehensive database of repetitive elements from diverse eukaryotic organisms. Currently, it contains over 3600 annotated sequences representing different families and subfamilies of repeats, many of which are unreported anywhere else. Each sequence is accompanied by a short description and references to the original contributors. Repbase Update includes Repbase Reports, an electronic journal publishing newly discovered transposable elements, and the Transposon Pub, a web-based browser of selected chromosomal maps of transposable elements. Sequences from Repbase Update are used to screen and annotate repetitive elements using programs such as Censor and RepeatMasker. Repbase Update is available on the worldwide web at http://www.girinst.org/Repbase_Update.html.

Animals↗

Rolling-circle transposons in eukaryotes.

All eukaryotic DNA transposons reported so far belong to a single category of elements transposed by the so-called "cut-and-paste" mechanism. Here, we report a previously unknown category of eukaryotic DNA transposons, Helitron, which transpose by rolling-circle replication. Autonomous Helitrons encode a 5'-to-3' DNA helicase and nuclease/ligase similar to those encoded by known rolling-circle replicons. Helitron-like transposons have conservative 5'-TC and CTRR-3' termini and do not have terminal inverted repeats. They contain 16- to 20-bp hairpins separated by 10--12 nucleotides from the 3'-end and transpose precisely between the 5'-A and T-3', with no modifications of the AT target sites. Together with their multiple diverged nonautonomous descendants, Helitrons constitute approximately 2% of both the Arabidopsis thaliana and Caenorhabditis elegans genomes and also colonize the Oriza sativa genome. Sequence conservation suggests that Helitrons continue to be transposed.

Amino Acid Sequence↗

The long terminal repeat of an endogenous retrovirus induces alternative splicing and encodes an additional carboxy-terminal sequence in the human leptin receptor.

The evolution of mammalian protein structure and regulation, specifically transcriptional and posttranscriptional regulation, may include among its tools the use of abundant retroviral long terminal repeats (LTRs). In particular, LTRs may be turned into switches for alternative splicing. This type of regulatory pathway is illustrated by the alternative splicing in the human leptin receptor (OBR). The human leptin receptor is involved in the control of important biological processes including energy expenditure, production of sex hormones, and activation of hemopoietic cells. OBRa and OBRb are the two major, alternatively spliced forms of the leptin receptor, called the "short form" and the "long form," respectively. We report that the OBRa short form is the result of a double splicing event which occurs within the LTR of the endogenous retrovirus HERV-K. Working as a switch of alternative splicing, this LTR also encodes the terminal 67 amino acid residues in OBRa. We suggest the possibility of transcriptional and posttranscriptional regulation of OBR expression by steroids that bind the LTR.

Alternative Splicing↗

Molecular paleontology of transposable elements from Arabidopsis thaliana.

We report results of a comprehensive computer-assisted analysis of new transposable elements (TEs) from Arabidopsis thaliana. Our analysis revealed several previously unknown pogo- and En/Spm-like families and two novel superfamilies of DNA transposons, Arnold and Harbinger. One of the En/Spm-like families (Atenspm) was found to be involved in generating satellite arrays in paracentromeric regions. Of the two superfamilies reported, Harbinger is distantly related to bacterial IS5-like insertion elements, and Arnold contains DNA transposons without terminal inverted repeats (TIRs), which were never reported in eukaryotes before. Furthermore, we report a large number of young and diverse copia-like autonomous and nonautonomous retroelements and discuss their potential evolutionary relationship with mammalian retroviruses. The A. thaliana genome harbors copia-like retroelements which encode a putative env-like protein reported previously in the SIRE-1 retrotransposon from soybean. Finally, we demonstrate a nonrandom chromosomal distribution of the most abundant A. thaliana TEs clustered in the first half of chromosome II, which includes the centromeric region. The families of TEs from A. thaliana are relatively young, extremely diverse and much smaller than those from mammalian genomes. We discuss the potential factors determining similarities and differences in the evolution of TEs in mammals and A. thaliana.

Amino Acid Sequence↗

Sectorial mutagenesis by transposable elements.

Transposable elements (TEs) generate insertions and cause other mutations in the genomic DNA. It is proposed that during co-evolution between TEs and eukaryotic genomes, an optimal path of the insertion mutagenesis is determined by the surviving TEs. These TEs can become semi-permanently established, chromatin-regulated 'source' or 'mutator genes', responsible for targeting insertion mutations to specific chromosomal regions. Such mutations can manifest themselves in non-random distribution patterns of interspersed repeats in eukaryotic chromosomes. In this paper we discuss specific models,examples and implications of optimized mutagenesis in eukaryotes.

Base Sequence↗

The BC200 RNA gene and its neural expression are conserved in Anthropoidea (Primates).

The gene encoding BC200 RNA arose from a monomeric Alu element. Subsequently, the RNA had been recruited or exapted into a function of the nervous system. Here we confirm the presence of the BC200 gene in several primate species among the Anthropoidea. The period following the divergence of New World monkeys and Old World monkeys from their common ancestor is characterized by a significantly higher substitution rate in the examined 5' flanking region than in the BC200 RNA coding region itself. Furthermore, the conservation of CpG dimers in the RNA coding region (200 bp) is drastically increased compared to the 5' flanking region (approximately 400 bp) over all 12 species examined. Finally, the brain-specific expression pattern of BC200 RNA and its presence as a ribonucleoprotein particle (RNP) are conserved in Old World and New World monkeys. Our studies indicate that the gene encoding BC200 RNA was created at least 35-55 million years ago and its presence, mode of expression, and association with protein(s) as an RNP are under selective pressure.

Animals↗

Mobile genetic elements, chiasmata, and the unique organization of beta-heterochromatin.

Beta-heterochromatin in Drosophila and the Syrian hamster share a similar DNA organization, few unique sequences, and scrambled repeats of mobile elements without tandem repetition. DNA in alpha-heterochromatin is tandemly repetitious, and we now show that the repeat unit can either contain or lack a mobile element. The tandem repeat organization of alpha-heterochromatin is presumably due to a concertina-like mechanism of unequal exchange between repeat units. Although both heterochromatin types are late replicating and can incorporate mobile retroposons, the sequence distinction between the two heterochromatins appears to be due to a property conferred by chiasmata upon the process of homologous recombination in beta-heterochromatin but not in alpha-heterochromatin. Chiasmata seem to suppress the concertina mechanism of unequal exchange and impart to beta-heterochromatin its nontandem, scrambled repeat organization.

Animals↗

MER53, a non-autonomous DNA transposon associated with a variety of functionally related defense genes in the human genome.

We report a new medium reiteration frequency repeat MER53 present in human and mammalian genomes. A 189 bp MER53 consensus sequence has been reconstructed based on the computer analysis of GenBank sequences. TA target site duplication and terminal inverted repeats indicate that the MER53 repeat is a non-autonomous DNA transposon related to the mariner family. Two MER53 repeats were found integrated within different mobile elements. We have found that most of the genes harboring the MER53 repeat are involved in the host defense system. The reasons for this non-random distribution of the repeat are discussed.

Animals↗

[Evolution of Alu repeats: dynamics of distribution in genome].

A mathematical model of evolutionary dynamics of Alu repeats' number in the human genome has been worked out. The model permitted us to observe the dynamics of propagation of Alu repeats within the genome and to evaluate such important parameters of the process mentioned as the rates of transposition (insertion of new copies into the genome) and excision of repeats. The peculiarities of the control of Alu repeats' number in the genome have been discussed, based on the data obtained.

Genome, Human↗

[Evolution of Alu repeats. Imitation model].

At present, nucleotide sequences of 100 different Alu repeats are known, i.e. 0.01% of the total number of Alu repeats in the genome. It is clear that one can not refer the evolutionary characteristics of Alu repeats obtained from the analysis of the available limited sample to all Alu repeats comprised in the genome, without additional statistical estimations. For supplementary investigation of such average evolutionary characteristics as the extent of intraspecific divergence, the rate of Alu repeats transposition (insertion, excision), we used the method of imitation simulation of the process of Alu repeats transposition in the genome. As a result of simulation, phylogenetic relations were obtained among all Alu repeats. It was shown that the evolutionary characteristics evaluated for different samples of repeats were similar. It was proved that the extent of divergence of Alu repeats in the model is twice as small as that evaluated, according to the real data (0.15, instead of 0.3). Possible reasons for such discrepancy have been discussed.

Genome, Human↗

[Evolutionary significance of the presence in mobile genetic elements of regulatory sites reacting to the environment. Regulatory site as a trigger].

A mathematical model of the Markov's process type describing the duplicative transposition of mobile genetic elements (MGE) has been developed. The possible role of MGE containing regulatory sites activated under unfavourable conditions has been considered. An analysis of the model has shown that there may be such regimes of environmental changes (sharp but random changes of the environment parameters) when sufficiently reliable survival of population is dependent on such MGE.

Animals↗

[Presence in the mobile genetic elements of regions homologous to the heat shock regulatory site].

The results of contextual analysis of 13 different mobile genetical elements (MGE) MDG1, MDG2, MDG3, MDG4, HOBO, P, F, MDG 17.6, H. M. S. Beagle, CIN1, BS1, TDD1, EV1 are presented. A search for regions revealing marked and statistically non-random homology with the consensus sequence of the heat-shock regulatory site (HSRS) has been carried out in these elements. Seven MGE (MDG1, MDG4, HOBO, P, CIN1, BS1, EV1) were shown to contain the regions of non-random homology with the HSRS consensus and the real HSRS. Evolutionary significance of connection between the environment and genetical cell system, based on the transcriptional activation of mobile genetical elements by heat-shock and some other factors, has been discussed.

Animals↗

Identification of new medium reiteration frequency repeats in the genomes of Primates, Rodentia and Lagomorpha.

We report eleven new families of MEdium Reiteration frequency (MER) interspersed repeats in the genomes of Primates, Rodentia, and Lagomorpha. Two families of the human repeats, MER 46 and MER 47, represent non-autonomous DNA transposons. These sequences are flanked by TA target site duplications and have terminal inverted repeats (TIRs) similar to TIRs of DNA transposons. The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. A potential involvement of some of the reported MER repeats in the regulation of transcription and genetic rearrangements is suggested. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu family.

Animals↗