http://www.mobilednajournal.com The most accessed research articles published by Mobile DNA 2012-01-26T00:00:00Z Background: Although humans and chimpanzees have accumulated significant differences in a number of phenotypic traits since diverging from a common ancestor about six million years ago, their genomes are more than 98.5% identical at protein-coding loci. This modest degree of nucleotide divergence is not sufficient to explain the extensive phenotypic differences between the two species. It has been hypothesized that the genetic basis of the phenotypic differences lies at the level of gene regulation and is associated with the extensive insertion and deletion (INDEL) variation between the two species. To test the hypothesis that large INDELs (80 to 12,000 bp) may have contributed significantly to differences in gene regulation between the two species, we categorized human-chimpanzee INDEL variation mapping in or around genes and determined whether this variation is significantly correlated with previously determined differences in gene expression. Results: Extensive, large INDEL variation exists between the human and chimpanzee genomes. This variation is primarily attributable to retrotransposon insertions within the human lineage. There is a significant correlation between differences in gene expression and large human-chimpanzee INDEL variation mapping in genes or in proximity to them. Conclusions: The results presented herein are consistent with the hypothesis that large INDELs, particularly those associated with retrotransposons, have played a significant role in human-chimpanzee regulatory evolution. http://www.mobilednajournal.com/content/2/1/13 Nalini Polavarapu Gaurav Arora Vinay Mittal John McDonald Mobile DNA 2011, null:13 2011-10-25T00:00:00Z doi:10.1186/1759-8753-2-13 /content/figures/1759-8753-2-13-toc.gif Mobile DNA 1759-8753 ${item.volume} 13 2011-10-25T00:00:00Z XML Background: Transposition in the IS3, IS30, IS21 and IS256 insertion sequence(IS) families utilizes an unconventional 2-step pathway. The Step I figure-of-eight intermediate, produced from asymmetric single strand cleavage and joining circularization reactions, is converted into a double stranded minicircle; its junction, the MCJ,[abutted left(IRL)and right(IRR)ends] is the substrate for symmetrical transesterification attacks on target DNA in Step II. This suggests intrinsically different synaptic complexes (SC) for each step. Because transposases of these ISs bind poorly to cognate DNA, comparative biophysical analyses of SC I and SC II have proven elusive. Here we utilize successfully, a native, soluble, active, GFP-tagged fusion derivative of the IS2 transposase that creates fully formed complexes with single-end and MCJ substrates, in hydroxyl radical footprinting experiments. Results: IS2 Step I reactions are physically and biochemically asymmetric with IRL the recipient end, lacking donor function. In SC I, different protection patterns of the cleavage domains (CDs) of IRR (extensive in cis) and IRL (selective in trans) at one active catalytic center (the IRR CC), are related to their donor and recipient functions. In SC II, an MCJ substrate showed extensive protection of both CDs, IRL in trans and the abutted IRR CD in cis - the first phase of the complex. An MCJ substrate precleaved at the 3' end of IRR, revealed a temporary transition state with the IRL CD disengaged from the protein. We propose that in SC II, sequential 3' cleavages of the abutted CDs bound at the same CC, trigger a conformational change, allowing the IRL CD to complex to its cognate CC - the second phase. Corroborating data from enhanced residues and curvature propensity plots suggest that CD to CD interactions in SC I and SC II require IRL to assume a bent structure, to facilitate binding in trans. Conclusions: Different transpososomes are assembled in each step of the IS2 transposition pathway. Recipient versus donor functions of the IRL CD in SC I and SC II and the proposed conformational change in SC II that precedes the symmetrical IRL and IRR donor attacks on target DNA, highlight the differences. http://www.mobilednajournal.com/content/3/1/1 Leslie Lewis Mekbib Astatke Peter Umekubo Shaheen Alvi Robert Saby Jehan Afrose Pedro Oliveira Gabriel Monteiro Duarte Prazeres Mobile DNA 2012, null:1 2012-01-26T00:00:00Z doi:10.1186/1759-8753-3-1 /content/figures/1759-8753-3-1-toc.gif Mobile DNA 1759-8753 ${item.volume} 1 2012-01-26T00:00:00Z PDF Scientific history has had a profound effect on the theories of evolution. At the beginning of the 21st century, molecular cell biology has revealed a dense structure of information-processing networks that use the genome as an interactive read-write (RW) memory system rather than an organism blueprint. Genome sequencing has documented the importance of mobile DNA activities and major genome restructuring events at key junctures in evolution: exon shuffling, changes in cis-regulatory sites, horizontal transfer, cell fusions and whole genome doublings (WGDs). The natural genetic engineering functions that mediate genome restructuring are activated by multiple stimuli, in particular by events similar to those found in the DNA record: microbial infection and interspecific hybridization leading to the formation of allotetraploids. These molecular genetic discoveries, plus a consideration of how mobile DNA rearrangements increase the efficiency of generating functional genomic novelties, make it possible to formulate a 21st century view of interactive evolutionary processes. This view integrates contemporary knowledge of the molecular basis of genetic change, major genome events in evolution, and stimuli that activate DNA restructuring with classical cytogenetic understanding about the role of hybridization in species diversification. http://www.mobilednajournal.com/content/1/1/4 James Shapiro Mobile DNA 2010, null:4 2010-01-25T00:00:00Z doi:10.1186/1759-8753-1-4 Mobile DNA and evolution in the 21st century Jim Shapiro reviews the study of mobile genetic elements since their discovery, and considers how insights into their mechanisms of genomic rearrangement can inform evolutionary theory. /content/figures/1759-8753-1-4-toc.gif Mobile DNA 1759-8753 ${item.volume} 4 2010-01-25T00:00:00Z XML Non-long terminal repeat (non-LTR) retrotransposons are present in most eukaryotic genomes. In some species, such as humans, these elements are the most abundant genome sequence and continue to replicate to this day, creating a source of endogenous mutations and potential genotoxic stress. This review will provide a general outline of the replicative cycle of non-LTR retrotransposons. Recent findings regarding the host regulation of non-LTR retrotransposons will be summarized. Finally, future directions of interest will be discussed. http://www.mobilednajournal.com/content/1/1/15 Jeffrey Han Mobile DNA 2010, null:15 2010-05-12T00:00:00Z doi:10.1186/1759-8753-1-15 /content/figures/1759-8753-1-15-toc.gif Mobile DNA 1759-8753 ${item.volume} 15 2010-05-12T00:00:00Z XML Background: Integrons are found in hundreds of environmental bacterial species, but are mainly known as the agents responsible for the capture and spread of antibiotic-resistance determinants between Gram-negative pathogens. The SOS response is a regulatory network under control of the repressor protein LexA targeted at addressing DNA damage, thus promoting genetic variation in times of stress. We recently reported a direct link between the SOS response and the expression of integron integrases in Vibrio cholerae and a plasmid-borne class 1 mobile integron. SOS regulation enhances cassette swapping and capture in stressful conditions, while freezing the integron in steady environments. We conducted a systematic study of available integron integrase promoter sequences to analyze the extent of this relationship across the Bacteria domain. Results: Our results showed that LexA controls the expression of a large fraction of integron integrases by binding to Escherichia coli-like LexA binding sites. In addition, the results provide experimental validation of LexA control of the integrase gene for another Vibrio chromosomal integron and for a multiresistance plasmid harboring two integrons. There was a significant correlation between lack of LexA control and predicted inactivation of integrase genes, even though experimental evidence also indicates that LexA regulation may be lost to enhance expression of integron cassettes. Conclusions: Ancestral-state reconstruction on an integron integrase phylogeny led us to conclude that the ancestral integron was already regulated by LexA. The data also indicated that SOS regulation has been actively preserved in mobile integrons and large chromosomal integrons, suggesting that unregulated integrase activity is selected against. Nonetheless, additional adaptations have probably arisen to cope with unregulated integrase activity. Identifying them may be fundamental in deciphering the uneven distribution of integrons in the Bacteria domain. http://www.mobilednajournal.com/content/2/1/6 Guillaume Cambray Neus Sanchez-Alberola Susana Campoy Emilie Guerin Sandra Da Re Bruno Gonzalez-Zorn Marie-Cecile Ploy Jordi Barbe Didier Mazel Ivan Erill Mobile DNA 2011, null:6 2011-04-30T00:00:00Z doi:10.1186/1759-8753-2-6 /content/figures/1759-8753-2-6-toc.gif Mobile DNA 1759-8753 ${item.volume} 6 2011-04-30T00:00:00Z XML Transposable elements (TEs) comprise a large fraction of mammalian genomes. A number of these elements are actively jumping in our genomes today. As a consequence, these insertions provide a source of genetic variation and, in rare cases, these events cause mutations that lead to disease. Yet, the extent to which these elements impact their host genomes is not completely understood. This review will summarize our current understanding of the mechanisms underlying transposon regulation and the contribution of TE insertions to genetic diversity in the germline and in somatic cells. Finally, traditional methods and emerging technologies for identifying transposon insertions will be considered. http://www.mobilednajournal.com/content/1/1/21 Kathryn O'Donnell Kathleen Burns Mobile DNA 2010, null:21 2010-09-02T00:00:00Z doi:10.1186/1759-8753-1-21 /content/figures/1759-8753-1-21-toc.gif Mobile DNA 1759-8753 ${item.volume} 21 2010-09-02T00:00:00Z XML Background: How new forms arise in nature has engaged evolutionary biologists since Darwin's seminal treatise on the origin of species. Transposable elements (TEs) may be among the most important internal sources for intraspecific variability. Thus, we aimed to explore the temporal dynamics of several TEs in individual genotypes from a small, marginal population of Aegilops speltoides. A diploid cross-pollinated grass species, it is a wild relative of the various wheat species known for their large genome sizes contributed by an extraordinary number of TEs, particularly long terminal repeat (LTR) retrotransposons. The population is characterized by high heteromorphy and possesses a wide spectrum of chromosomal abnormalities including supernumerary chromosomes, heterozygosity for translocations, and variability in the chromosomal position or number of 45S and 5S ribosomal DNA (rDNA) sites. We propose that variability on the morphological and chromosomal levels may be linked to variability at the molecular level and particularly in TE proliferation. Results: Significant temporal fluctuation in the copy number of TEs was detected when processes that take place in small, marginal populations were simulated. It is known that under critical external conditions, outcrossing plants very often transit to self-pollination. Thus, three morphologically different genotypes with chromosomal aberrations were taken from a wild population of Ae. speltoides, and the dynamics of the TE complex traced through three rounds of selfing. It was discovered that: (i) various families of TEs vary tremendously in copy number between individuals from the same population and the selfed progenies; (ii) the fluctuations in copy number are TE-family specific; (iii) there is a great difference in TE copy number expansion or contraction between gametophytes and sporophytes; and (iv) a small percentage of TEs that increase in copy number can actually insert at novel locations and could serve as a bona fide mutagen. Conclusions: We hypothesize that TE dynamics could promote or intensify morphological and karyotypical changes, some of which may be potentially important for the process of microevolution, and allow species with plastic genomes to survive as new forms or even species in times of rapid climatic change. http://www.mobilednajournal.com/content/1/1/6 Alexander Belyayev Ruslan Kalendar Leonid Brodsky Eviatar Nevo Alan Schulman Olga Raskina Mobile DNA 2010, null:6 2010-02-01T00:00:00Z doi:10.1186/1759-8753-1-6 /content/figures/1759-8753-1-6-toc.gif Mobile DNA 1759-8753 ${item.volume} 6 2010-02-01T00:00:00Z XML Background: The centromeric and pericentromeric regions of plant chromosomes are colonized by Ty3/gypsy retrotransposons, which, on the basis of their reverse transcriptase sequences, form the chromovirus CRM clade. Despite their potential importance for centromere evolution and function, they have remained poorly characterized. In this work, we aimed to carry out a comprehensive survey of CRM clade elements with an emphasis on their diversity, structure, chromosomal distribution and transcriptional activity. Results: We have surveyed a set of 190 CRM elements belonging to 81 different retrotransposon families, derived from 33 host species and falling into 12 plant families. The sequences at the C-terminus of their integrases were unexpectedly heterogeneous, despite the understanding that they are responsible for targeting to the centromere. This variation allowed the division of the CRM clade into the three groups A, B and C, and the members of each differed considerably with respect to their chromosomal distribution. The differences in chromosomal distribution coincided with variation in the integrase C-terminus sequences possessing a putative targeting domain (PTD). A majority of the group A elements possess the CR motif and are concentrated in the centromeric region, while members of group C have the type II chromodomain and are dispersed throughout the genome. Although representatives of the group B lack a PTD of any type, they appeared to be localized preferentially in the centromeres of tested species. All tested elements were found to be transcriptionally active. Conclusions: Comprehensive analysis of the CRM clade elements showed that genuinely centromeric retrotransposons represent only a fraction of the CRM clade (group A). These centromeric retrotransposons represent an active component of centromeres of a wide range of angiosperm species, implying that they play an important role in plant centromere evolution. In addition, their transcriptional activity is consistent with the notion that the transcription of centromeric retrotransposons has a role in normal centromere function. http://www.mobilednajournal.com/content/2/1/4 Pavel Neumann Alice Navratilova Andrea Koblizkova Eduard Kejnovsky Eva Hribova Roman Hobza Alex Widmer Jaroslav Dolezel Jiri Macas Mobile DNA 2011, null:4 2011-03-03T00:00:00Z doi:10.1186/1759-8753-2-4 /content/figures/1759-8753-2-4-toc.gif Mobile DNA 1759-8753 ${item.volume} 4 2011-03-03T00:00:00Z XML Transposable elements can be viewed as natural DNA transfer vehicles that, similar to integrating viruses, are capable of efficient genomic insertion. The mobility of class II transposable elements (DNA transposons) can be controlled by conditionally providing the transposase component of the transposition reaction. Thus, a DNA of interest (be it a fluorescent marker, a small hairpin (sh)RNA expression cassette, a mutagenic gene trap or a therapeutic gene construct) cloned between the inverted repeat sequences of a transposon-based vector can be used for stable genomic insertion in a regulated and highly efficient manner. This methodological paradigm opened up a number of avenues for genome manipulations in vertebrates, including transgenesis for the generation of transgenic cells in tissue culture, the production of germline transgenic animals for basic and applied research, forward genetic screens for functional gene annotation in model species, and therapy of genetic disorders in humans. Sleeping Beauty (SB) was the first transposon shown to be capable of gene transfer in vertebrate cells, and recent results confirm that SB supports a full spectrum of genetic engineering including transgenesis, insertional mutagenesis, and therapeutic somatic gene transfer both ex vivo and in vivo. The first clinical application of the SB system will help to validate both the safety and efficacy of this approach. In this review, we describe the major transposon systems currently available (with special emphasis on SB), discuss the various parameters and considerations pertinent to their experimental use, and highlight the state of the art in transposon technology in diverse genetic applications. http://www.mobilednajournal.com/content/1/1/25 Zoltan Ivics Zsuzsanna Izsvak Mobile DNA 2010, null:25 2010-12-07T00:00:00Z doi:10.1186/1759-8753-1-25 /content/figures/1759-8753-1-25-toc.gif Mobile DNA 1759-8753 ${item.volume} 25 2010-12-07T00:00:00Z XML Background: Endogenous retroviruses (ERVs) and ERV-like sequences comprise 8% of the human genome. A hitherto unknown proportion of ERV loci are transcribed and thus contribute to the human transcriptome. A small proportion of these loci encode functional proteins. As the role of ERVs in normal and diseased biological processes is not yet established, transcribed ERV loci are of particular interest. As more transcribed ERV loci are likely to be identified in the near future, the development of a systematic nomenclature is important to ensure that all information on each locus can be easily retrieved. Results: Here we present a revised nomenclature of transcribed human endogenous retroviral loci that sorts loci into groups based on Repbase classifications. Each symbol is of the format ERV + group symbol + unique number. Group symbols are based on a mixture of Repbase designations and well-supported symbols used in the literature. The presented guidelines will allow newly identified loci to be easily incorporated into the scheme. Conclusions: The naming system will be employed by the HUGO Gene Nomenclature Committee for naming transcribed human ERV loci. We hope that the system will contribute to clarifying a certain aspect of a sometimes confusing nomenclature for human endogenous retroviruses. The presented system may also be employed for naming transcribed loci of human non-ERV repeat loci. http://www.mobilednajournal.com/content/2/1/7 Jens Mayer Jonas Blomberg Ruth Seal Mobile DNA 2011, null:7 2011-05-04T00:00:00Z doi:10.1186/1759-8753-2-7 /content/figures/1759-8753-2-7-toc.gif Mobile DNA 1759-8753 ${item.volume} 7 2011-05-04T00:00:00Z XML