http://www.mobilednajournal.com The most accessed research articles published by Mobile DNA 2012-04-30T00:00:00Z Background: Sequence analysis of the orangutan genome revealed that recent proliferative activity of Alu elements has been uncharacteristically quiescent in the Pongo (orangutan) lineage, compared to all previously studied primate genomes. With relatively few young polymorphic insertions, the genomic landscape of the orangutan seemed like the ideal place to search for a driver, or source element of Alu retrotransposition. Results: Here we report the identification of a nearly pristine insertion possessing all the known putative hallmarks of a retrotranspositionally competent Alu element. It is located in intronic sequence of the DGKB gene on chromosome 7 and is highly conserved in Hominidae (the great apes), but absent from Hylobatidae (gibbon and siamang). We provide evidence for the evolution of a lineage-specific subfamily of this shared Alu insertion in orangutans and possibly the lineage leading to humans. In the orangutan genome, this insertion contains three orangutan-specific diagnostic mutations which are characteristic of the youngest polymorphic Alu subfamily, AluYe5b5_Pongo. In the Homininae lineage (human, chimpanzee and gorilla) this insertion has acquired three different mutations which are also found in a single human-specific Alu insertion. Conclusions: This seemingly stealth like amplification, ongoing at a very low rate over millions of years of evolution, suggests that this shared insertion may represent an ancient backseat driver of Alu element expansion. http://www.mobilednajournal.com/content/3/1/8 Jerilyn Walker Miriam Konkel Brygg Ullmer Christopher Monceaux Oliver Ryder Robert Hubley Arian Smit Mark Batzer Mobile DNA 2012, null:8 2012-04-30T00:00:00Z doi:10.1186/1759-8753-3-8 Orangutans harbor ancient primate Alu A source Alu element has been identified in the Orangutan genome, providing support for 'ancient backseat drivers' of the amplification of Alu elements in primate genomes, ongoing through millions of years of evolution. /content/figures/1759-8753-3-8-toc.gif Mobile DNA 1759-8753 ${item.volume} 8 2012-04-30T00:00:00Z 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 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: 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 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 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: The H-NS protein is a global regulator of gene expression in bacteria and can also bind transposition complexes (transpososomes). In Tn5 transposition H-NS promotes transpososome assembly in vitro and disruption of the hns gene causes a modest decrease in Tn5 transposition (three- to five-fold). This is consistent with H-NS acting as a positive regulator of Tn5 transposition. Molecular determinants for H-NS binding to the Tn5 transpososome have not been determined, nor has the strength of the interaction been established. There is also uncertainty as to whether H-NS regulates Tn5 transposition in vivo through an interaction with the transposition machinery as disruption of the hns gene has pleiotropic effects on Escherichia coli, the organism used in this study. Results: In the current work we have further examined determinants for H-NS binding to the Tn5 transpososome through both mutational studies on Tn5 termini (or 'transposon ends') and protein-protein cross-linking analysis. We identify mutations in two different segments of the transposon ends that abrogate H-NS binding and characterize the affinity of H-NS for wild type transposon ends in the context of the transpososome. We also show that H-NS forms cross-links with the Tn5 transposase protein specifically in the transpososome, an observation consistent with the two proteins occupying overlapping binding sites in the transposon ends. Finally, we make use of the end mutations to test the idea that H-NS exerts its impact on Tn5 transposition in vivo by binding directly to the transpososome. Consistent with this possibility, we show that two different end mutations reduce the sensitivity of the Tn5 system to H-NS regulation. Conclusions: H-NS typically regulates cellular functions through its potent transcriptional repressor function. Work presented here provides support for an alternative mechanism of H-NS-based regulation, and adds to our understanding of how bacterial transposition can be regulated. http://www.mobilednajournal.com/content/3/1/7 Crystal Whitfield Brian Shilton David Haniford Mobile DNA 2012, null:7 2012-04-13T00:00:00Z doi:10.1186/1759-8753-3-7 /content/figures/1759-8753-3-7-toc.gif Mobile DNA 1759-8753 ${item.volume} 7 2012-04-13T00:00:00Z XML Background: Tyrosine-based site-specific recombinases (TBSSRs) are DNA breaking-rejoining enzymes, which in bacterial genomes play a major role in the comings and goings of mobile genetic elements (MGEs) such as temperate phage genomes, integrated conjugative elements (ICEs) or integron cassettes, but also in the segregation of plasmids and chromosomes, the resolution of plasmid dimers and of co-integrates resulting from the replicative transposition of transposons. With the aim of improving the annotation of TBSSR genes in genomic sequences and databases, which so far is far from robust, we built a set of over 1300 TBSSR protein sequences tagged with their genome of origin. We organized them in families to investigate i) whether TBSSRs tend to be more conserved within than between classes of MGE types and ii) whether the (sub)families may help in understanding more about the function of TBSSRs associated in tandem or trios, found on plasmids and chromosomes. Results: 67% of the TBSSRs in our set are MGE type specific. We define a new class of Actinobacterial transposons, related to Tn554, with one abnormally long TBSSR gene and a regular sized one, and further characterize numerous TBSSRs trios present in plasmids and chromosomes of alpha and beta-proteobacteria. Conclusions: The simple in silico procedure described here, which uses a set of reference TBSSRs originating from defined MGE types, could contribute to greatly improve the annotation of tyrosine-based site-specific recombinases belonging to well characterized types of MGEs. It also reveals TBSSRs families belonging to genetic entities that by their distribution among bacterial taxa, seem to contribute to lateral gene transfer. http://www.mobilednajournal.com/content/3/1/6 Rob Van Houdt Raphael Leplae Max Mergeay Ariane Toussaint Gipsi Lima-Mendez Mobile DNA 2012, null:6 2012-04-13T00:00:00Z doi:10.1186/1759-8753-3-6 /content/figures/1759-8753-3-6-toc.gif Mobile DNA 1759-8753 ${item.volume} 6 2012-04-13T00:00:00Z PDF 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 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