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At least 793 records · Page 44Linked to original sources
PubMed2005

Transposable elements--is there a link between evolution and cancer?

Currently, the most predominant theory concerning the formation of cancer is that it is a genetic accident. Accordingly, various agents are thought to cause DNA damage which then subsequently activates oncogenes and inactivates tumor suppressor genes. This article, however, describes a theory that interprets cancer as a misguided adaptation. Stressors, which cannot be compensated for with the usual cell possibilities might arouse evolutionary mechanisms intended to create new protein variants. One of these is the activation of transposable elements which leads to a reformatting of the genome. The result of this process is either a cell that survives very well under stress (and will, therefore, never be detected), a dead cell (in case the process is ineffective), or a more or less abnormal and harmful cell that builds up a new but cancerous organ. This theory explains the complex genetic alterations which are present in almost all cancer cells. It also explains the action of non-mutagenic carcinogens. As part of the reformatting process of the cancer cell genome, activation of oncogenes and inactivation of tumor suppressor genes are not stochastic events but the result of an unlucky genomic composition.

Carcinogens↗
PubMed1998

Drosophila melanogaster histone H2B retropseudogene is inserted into a region rich in transposable elements.

We have isolated and characterized the genomic sequence of a Drosophila melanogaster histone H2B pseudogene that is localized outside of the cluster of the replication-dependent histone genes and has all the properties of a retropseudogene. It is highly homologous to the transcribed region of the D. melanogaster histone H2B gene, but not to its flanking regions, and is surrounded by short direct repeats. The pseudogene contains several point mutations that preclude its translation. The sequence of the 3' region of this pseudogene is compatible with the hypothesis that the 3' terminal stem-loop structure of the histone H2B mRNA has served as a primer for the reverse transcription event from which this pseudogene originated. Analysis of the regions flanking the histone H2B pseudogene revealed the presence of three different types of transposable elements, suggesting that this chromosomal locus represents a hotspot for transposition.

Amino Acid Sequence↗
PubMed1983

A transposable element inserted just 5' to a Drosophila glue protein gene alters gene expression and chromatin structure.

The Drosophila Sgs-4 gene directs the developmentally regulated production of a glue protein in the salivary glands of mature larvae. Previous work suggests that Sgs-4 expression requires a remote upstream region that becomes hypersensitive to DNAase I digestion when the gene is active. Here we describe a variant Sgs-4 locus that has a 1.3 kb DNA insert separating the gene from the remote hypersensitive region. This insert defines a new family of transposable elements that we call hobo. Expression from the variant locus is reduced 50 to 100 fold, and rather than the one, normal Sgs-4 transcript, there are now four transcripts, two starting within the hobo element. These multiple transcripts are still expressed only in late larval salivary glands, implying that developmental regulation is unaffected by changes in the site of transcript initiation. When Sgs-4 is active, the remote DNAase I-hypersensitive region, now even more remote due to the insert, still forms over its normal sequences. In contrast, new hypersensitive sites form within hobo near the starts of the new transcripts.

Animals↗
PubMed1997

Insertions of a novel class of transposable elements with a strong target site preference at the r locus of maize.

The r locus of maize regulates anthocyanin synthesis in various tissues of maize through the production of helix-loop-helix DNA binding proteins capable of inducing expression of structural genes in the anthocyanin biosynthetic pathway. The complex r variant, R-r: standard (R.r), undergoes frequent mutation through a variety of mechanisms including displaced synapsis and crossing over, and intrachromosomal recombination. Here we report a new mechanism for mutation at the R-r complex: insertion of a novel family of transposable elements. Because the elements were first identified in the R-p gene of the R-r complex, they have been named P instability Factor (PIF). Two different PIF elements were cloned and found to have identical sequences at their termini but divergent internal sequences. In addition, the PIF elements showed a marked specificity of insertion sites. Six out of seven PIF-containing derivatives examined had an element inserted at an identical location. Two different members of the PIF element family were identified at this position. The seventh PIF-containing derivative examined had the element inserted at a distinct position within r. Even at this location, however, the element inserted into a conserved target sequence. The timing of PIF excision is unusual. Germinal excision rates can range up to several percent of progeny. Yet somatic sectors are rare, even in lines exhibiting high germinal reversion rates.

Anthocyanins↗
PubMed1983

cA lectin gene insertion has the structural features of a transposable element.

The single gene Le1, coding for soybean seed lectin, was compared to le1, a naturally occurring mutant allele containing a 3.4 kb insertion within its coding region. Le1 is devoid of introns and produces a 1.0 kb mRNA. It codes for a signal sequence of 32 amino acids and a mature protein of 253 amino acids. With the exception of six single-base substitutions, the coding and flanking sequences in le1 are identical with those in the uninterrupted gene. The insertion termini are imperfect inverted repeats flanked by a 3 bp duplication of lectin target DNA. Inverted repeats within the lectin gene are located symmetrically with respect to the insertion site and are homologous to a region of the insertion termini. These molecular traits conform with the structural aspects of transposable elements in other organisms and imply some degree of site specificity.

Amino Acids↗
PubMedDate not supplied

Transposable elements as mutator genes in evolution.

Strains of the bacterium Escherichia coli harbouring genes that increase mutation rates are known to have an evolutionary advantage in chemostat competition over otherwise isogeneic strains with lower mutation rates. This advantage is frequency-dependent, the mutator strain being favoured only above a starting ratio of approximately 5 x 10(-5), and it results from the fact that the necessary beneficial mutations cannot be generated in a mutator population below a certain size. Here we consider the possibility that the mutagenic properties of transposable elements confer an advantage in the same manner as mutator genes. A previous report has shown that the transposon Tn5 increases the fitness of E. coli in chemostats, although the reason for this effect has not been established. Our results show that the transposon Tn10 also confers an advantage in chemostats. In addition, we find that (1) this advantage, like that associated with mutator genes, is frequency-dependent, (2) whenever the Tn10 strains win, a segment of Tn10, probably its IS10 sequences, has undergone transposition to a new site, (3) the new insertions converge into a site contained within a 3.2 kilobase (kb) PvuII fragment of the genome, and (4) no transpositions are detected when the Tn10 population loses. We conclude that Tn10 confers an advantage by increasing the mutation rate of the host bacterium.

Biological Evolution↗
PubMedDate not supplied

Transposable elements controlling genetic instabilities in mammals.

It is proposed that the instabilities in gene action of some alleles at certain loci in the mouse (e.g., a, c, H-2 Mi, p, pe, T, Va, W), which do not seem to conform to traditional hypotheses of gene action, are better interpretable in the light of modern studies of transposable DNA elements (insertion sequences and transposons of prokaryotic organisms; controlling elements of maize; transposable controlling elements of Drosophila). Some phenotypic evidence in the mouse in support of this hypothesis is presented for the a, Mi, p, and W loci, which affect pigmentation.

Animals↗
PubMed1995

Characterization of Gandalf, a new inverted-repeat transposable element of Drosophila koepferae.

The cloning and characterization of Gandalf, a new DNA-transposing mobile element obtained from the Drosophila koepferae (repleta group) genome is described. A fragment of Gandalf was found in a middle repetitive clone that shows variable chromosomal localization. Restriction, Southern blot, PCR and sequencing analyses have shown that most Gandalf copies are about 1 kb long, are flanked by 12 bp inverted terminal repeats and contain subterminal repetitive regions on both sides of the element. As with other elements of the DNA-transposing type (known as the 'Ac family'), the Gandalf element generates 8 bp direct duplications at the insertion point. Coding region analysis has shown that the longer open reading frame found in Gandalf copies could encode part of a protein. However, whether or not the 1 kb copies of the element are actually the active transposons remains to be elucidated. Gandalf shows a very low copy number in D. buzzatii, a sibling species of D. koepferae. An attempt to induce interspecific hybrid dysgenesis in hybrids of these two species has been unsuccessful.

Animals↗
PubMed2005

Changes in race-specific virulence in Pseudomonas syringae pv. phaseolicola are associated with a chimeric transposable element and rare deletion events in a plasmid-borne pathogenicity island.

Virulence for bean and soybean is determined by effector genes in a plasmid-borne pathogenicity island (PAI) in race 7 strain 1449B of Pseudomonas syringae pv. phaseolicola. One of the effector genes, avrPphF, confers either pathogenicity, virulence, or avirulence depending on the plant host and is absent from races 2, 3, 4, 6, and 8 of this pathogen. Analysis of cosmid clones and comparison of DNA sequences showed that the absence of avrPphF from strain 1448A is due to deletion of a continuous 9.5-kb fragment. The remainder of the PAI is well conserved in strains 1448A and 1449B. The left junction of the deleted region consists of a chimeric transposable element generated from the fusion of homologs of IS1492 from Pseudomonas putida and IS1090 from Ralstonia eutropha. The borders of the deletion were conserved in 66 P. syringae pv. phaseolicola strains isolated in different countries and representing the five races lacking avrPphF. However, six strains isolated in Spain had a 10.5-kb deletion that extended 1 kb further from the right junction. The perfect conservation of the 28-nucleotide right repeat of the IS1090 homolog in the two deletion types and in the other 47 insertions of the IS1090 homolog in the 1448A genome strongly suggests that the avrPphF deletions were mediated by the activity of the chimeric mobile element. Our data strongly support a clonal origin for the races of P. syringae pv. phaseolicola lacking avrPphF.

Amino Acid Sequence↗
PubMed1985

Evolution of transposable elements: an IS10 insertion increases fitness in Escherichia coli.

Strains of Escherichia coli carrying Tn10, a transposon consisting of two IS10 insertion sequences flanking a segment encoding for a tetracycline-resistance determinant, gain a competitive advantage in chemostat cultures. All Tn10-bearing strains that increase in frequency during competition have a new IS10 insertion that is found in the same location in the genome of those strains. We mapped, by a gradient of transmission, the position of the new IS10 insertion. We examined 11 isolates whose IS10 insertion was deleted by recombinational crossing-over, and in all cases the competitive fitness of the isolates was decreased. These results show that the IS10-generated insertion increases fitness in chemostat cultures. We named the insertion fit::IS10 and suggest that transposable elements may speed the rate of evolution by promoting nonhomologous recombination between preexisting variations within a genome and thereby generating adaptive variation.

Biological Evolution↗
PubMed1984

A minor class of 5S rRNA genes in Saccharomyces cerevisiae X2180-1B, one member of which lies adjacent to a Ty transposable element.

In Saccharomyces cerevisiae the majority of the genes for 5S rRNA lie within a 9kb rDNA sequence that is present as 100-200 tandemly-repeated copies on Chromosome XII. Following our observations that about 10% of yeast 5S rRNA exists as minor variant sequences, we screened a collection of yeast DNA fragments cloned in lambda gt for 5S rRNA genes whose flanking sequences differed from those adjacent to 5S rRNA genes of the rDNA repeat. Three variant 5S rRNA genes were isolated on the basis of such dissimilarity to rDNA repeat sequences. They display a remarkable conservation of their DNA in the vicinity of the 5S coding region, and are examples of a minor form of 5S rRNA coding sequence present in a small number of copies in the yeast genome. These variant sequences appear to be transcribed as efficiently as 5S rRNA genes of the rDNA repeat. In one of our isolates of the variant sequence a Ty transposable element is inserted 145bp upstream of the initiation point for 5S rRNA synthesis.

Base Sequence↗
PubMed1984

Topological repression of gene activity by a transposable element.

The ebgA (evolved beta-galactosidase) gene of Escherichia coli was isolated as part of a 9.6-kilobase (kb) sequence cloned into plasmid pBR322. The position of the ebgA gene within that 9.6-kilobase sequence was identified by insertional inactivation by means of the transposon gamma-delta. In addition to the gamma-delta insertions that inactivate ebgA by disrupting the coding sequence, seven additional gamma-delta insertions reduce expression of the gene by a factor of greater than 200 by insertions elsewhere into the replicon. One of these insertions is into the pBR322 sequence itself. This action at a distance to reduce expression requires that gamma-delta is cis with respect to the ebgA gene. The effect is independent of the orientation or position of gamma-delta within the replicon, but it does depend both upon the orientation of the ebgA-bearing sequence within the replicon and upon the total size of the replicon. Transcription readthrough (promoter occlusion) does not explain this phenomenon, and we suggest that the presence of gamma-delta may alter the local supercoiling in the region of the ebgA promoter in such a way as to inhibit transcription. This repression by a transposable element appears to represent a novel mechanism for altering gene expression.

DNA Restriction Enzymes↗
PubMed1997

Nht1, a transposable element cloned from a dispensable chromosome in Nectria haematococca.

Certain isolates of the plant-pathogenic fungus Nectria haematococca mating population VI (MPVI) contain dispensable chromosomes that are unstable during sexual reproduction. Several of these chromosomes carry genes for phytoalexin detoxification and thus contribute to the pathogenic potential of this organism. A repeated DNA sequence, Nht1, was cloned from one of these dispensable chromosomes in N. haematococca MPVI. One copy of the repeated element (Nht1A) was completely sequenced. It is 2,198 bp long and it possesses incomplete inverted terminal repeats (ITRs) at each end. Nht1B, a partially sequenced copy of Nht1, has complete ITRs. Nht1A appears to contain 2 introns and encodes a protein of 550 amino acids that is highly similar to the protein encoded by the Fusarium oxysporum transposon, Fot1. Due to the presence of ITRs, its repeated nature, and its similarity to Fot1, we conclude that Nht1 is a transposable element. Within North American N. Haematococca MPVI populations, Nht1 is distributed discontinuously. Its copy number in different field isolates varies from zero to approximately 100 copies per genome. The Nht1A source isolate is estimated to contain nine to 11 copies of Nht1; at least six are on the chromosome from which Nht1A was cloned.

Amino Acid Sequence↗
PubMed1991

MEC: a transposable element from Chironomus thummi (diptera).

Two genomic clones, pC1.2 and p20D (containing inserts of 2.0 and 1.6 kb, respectively) were isolated from the A2b region to polytene chromosome IV of Chironomus thummi thummi salivary gland cells. Upon in situ hybridization to polytene chromosomes of C. thummi thummi and C. thummi piger, p20D DNA hybridized mainly over the A2b region of chromosome IV, whereas pC1.2 DNA hybridized to at least 90 sites distributed over all the chromosomes. A partial nucleotide sequence analysis showed that these clones were very similar and allowed the detection of a 596 bp insert in the pC1.2 clone. This insert possesses all of the essential features of a Class II transposable element and was called MEC. It carries a nearly perfect 107 bp terminal inverted repeat containing one mismatch and is flanked by a 5 bp direct repeat. The 372 bp central region contains a short open reading frame with a coding capacity of 58 amino acids.

Amino Acid Sequence↗
PubMed2003

Gene vector and transposable element behavior in mosquitoes.

The development of efficient germ-line transformation technologies for mosquitoes has increased the ability of entomologists to find, isolate and analyze genes. The utility of the currently available systems will be determined by a number of factors including the behavior of the gene vectors during the initial integration event and their behavior after chromosomal integration. Post-integration behavior will determine whether the transposable elements being employed currently as primary gene vectors will be useful as gene-tagging and enhancer-trapping agents. The post-integration behavior of existing insect vectors has not been extensively examined. Mos1 is useful as a primary germ-line transformation vector in insects but is inefficiently remobilized in Drosophila melanogaster and Aedes aegypti. Hermes transforms D. melanogaster efficiently and can be remobilized in this species. This element is also useful for creating transgenic A. aegypti, but its mode of integration in mosquitoes results in the insertion of flanking plasmid DNA. Hermes can be remobilized in the soma of A. aegypti and transposes using a common cut-and-paste mechanism; however, the element does not remobilize in the germ line. piggyBac can be used to create transgenic mosquitoes and occasionally integrates using a mechanism other than a simple cut-and-paste mechanism. Preliminary data suggest that remobilization is infrequent. Minos also functions in mosquitoes and, like the other gene vectors, appears to remobilize inefficiently following integration. These results have implications for future gene vector development efforts and applications.

Animals↗
PubMed1994

A transposable element can drive the concerted evolution of tandemly repetitious DNA.

Recombination and conversion have been proposed to drive the concerted evolution of tandemly repeated DNA sequences. However, specific correction events within the repeated genes of multicellular organisms have not been observed directly, so their nature has remained speculative. We investigated whether the excision of transposable P elements from tandemly repeated sequences would induce unequal gene conversion. Genetically marked elements located in a subtelomeric repeat were mobilized, and the structure of the region was analyzed in progeny. We observed that the number of repeats was frequently altered. Decreases were more common than increases, and this bias probably resulted from intrinsic mechanisms governing P element-induced double-strand break repair. Our results suggest that transposable elements play an important role in the evolution of repetitious DNA.

Animals↗
PubMed2004

Detection of transposable elements in Drosophila salivary gland polytene chromosomes by in situ hybridization.

In situ hybridization is particularly appropriate for mapping specific DNA sequences on polytene chromosomes of Drosophila and other dipterans. This technique is based on the recognition and binding of one labeled sequence (the probe) to homologous sequences on chromosomes fixed on a microscope slide. The probes are labeled with biotin or other nonradioactive products, and the probe signal can be detected as a thin line on the chromosomes, following the shape of the classical Giemsa-stained chromosome bands, thus allowing the detection of TE insertions within the range of 50 to 200 kb. In our laboratory we work on many individuals from natural populations, and as a result we process high numbers of slides hybridized with various DNA probes of transposable elements every day. Therefore, the in situ hybridization technique we use is a simplification of earlier published protocols. This chapter presents our simplified standard in situ hybridization protocol for labeling polytene chromosomes of Drosophila with biotin and a fluorescence stain (FISH).

Animals↗
PubMed2005

Evidence for a functional interaction between the Bari1 transposable element and the cytochrome P450 cyp12a4 gene in Drosophila melanogaster.

Previous studies of the genomic distribution of the transposon Bari1 in Drosophila melanogaster have revealed an element which is fixed at division 91F in over 90 lab and natural populations. Here we report about the structural and transcriptional features of the insertion site which was studied in sublines isolated from an exceptional Drosophila line polymorphic for the presence/absence of Bari1 at 91F. The insert is located at the 3' end of the cyp12a4 gene that belongs to the cytochrome P450 family. In flies with the insert the transcript of this gene encompasses 18 nucleotides of the transposon, it is shorter and is about tenfold more abundant compared to flies devoid of it. Although the hypothetical selective agent remains unknown, these data are suggestive of a selective advantage brought about by the Bari1 insert and are reminiscent of recent evidence for functional mutagenesis of cyp6g1, another P450 gene, brought about by Accord and Doc transposable elements in D. melanogaster and Drosophila simulans.

3' Untranslated Regions↗