Table of Contents

Volume 2, Issue 4

  July/August 2012

  Pages 169 - 201

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 Issue Catalogue (MARC XML)

IN THIS ISSUE

Open Access Article

In this issue of Mobile Genetic Elements

Elaine L. Ellerton
Pages 169 - 170
http://dx.doi.org/10.4161/mge.22169
Full Text | PDF




LETTERS TO THE EDITOR

Open Access Article

Harnessing the power of transposon mutagenesis for antibacterial target identification and evaluation

Timothy C. Meredith, Hao Wang, Patrick Beaulieu, Angelika Gründling and Terry Roemer
Pages 171 - 178
http://dx.doi.org/10.4161/mge.21647
Abstract | Full Text | PDF

Determining the mechanism of action of bacterial growth inhibitors can be a formidable challenge in the progression of small molecules into antibacterial therapies. To help address this bottleneck, we have developed a robust transposon mutagenesis system using a suite of outward facing promoters in order to generate a comprehensive range of expression genotypes in Staphylococcus aureus from which to select defined compound-resistant transposon insertion mutants. Resistance stemming from either gene or operon over/under-expression, in addition to deletion, provides insight into multiple factors that contribute to a compound’s observed activity, including means of cell envelope penetration and susceptibility to efflux. By profiling the entire resistome, the suitability of an antibacterial target itself is also evaluated, sometimes with unanticipated results. We herein show that for the staphylococcal signal peptidase (SpsB) inhibitors, modulating expression of lipoteichoic acid synthase (LtaS) confers up to a 100-fold increase in the minimal inhibitory concentration. As similarly efficient transposition systems are or will become established in other bacteria and cell types, we discuss the utility, limitations and future promise of Tnp mutagenesis for determining both a compound’s mechanism of action and in the evaluation of novel targets.

Open Access Article

Mobile genetic elements in the bacterial phylum Acidobacteria

Jean Challacombe and Cheryl Kuske
Pages 179 - 183
http://dx.doi.org/10.4161/mge.21943
Abstract | Full Text | PDF

Analysis of the genome of Candidatus Solibacter usitatus Ellin6076, a member of the phylum Acidobacteria, revealed a large number of genes associated with mobile genetic elements. These genes encoded transposases, insertion sequence elements and phage integrases. When the amino acid sequences of the mobile element-associated genes were compared, many of them had high (90–100%) amino acid sequence identities, suggesting that these genes may have recently duplicated and dispersed throughout the genome. Although phage integrase encoding genes were prevalent in the Can. S. usitatus Ellin6076 genome, no intact prophage regions were found. This suggests that the Can. S. usitatus Ellin6076 large genome arose by horizontal gene transfer via ancient bacteriophage and/or plasmid-mediated transduction, followed by widespread small-scale gene duplications, resulting in an increased number of paralogs encoding traits that could provide selective metabolic, defensive and regulatory advantages in the soil environment. Here we examine the mobile element repertoire of Can. S. usitatus Ellin6076 in comparison to other genomes from the Acidobacteria phylum, reviewing published studies and contributing some new analyses. We also discuss the presence and potential roles of mobile elements in members of this phylum that inhabit a variety of environments.




RESEARCH PAPER

Open Access Article

OrbId: Origin-based identification of microRNA targets

Teresa J. Filshtein, Craig O. Mackenzie, Maurice D. Dale, Paul S. Dela-Cruz, Dale M. Ernst, Edward A. Frankenberger, Chunyan He, Kaylee L. Heath, Andria S. Jones, Daniel K. Jones, Edward R. King, Maggie B. Maher, Travis J. Mitchell, Rachel R. Morgan, Sirisha Sirobhushanam, Scott D. Halkyard, Kiran B. Tiwari, David A. Rubin, Glen M. Borchert and Erik D. Larson
Pages 184 - 192
http://dx.doi.org/10.4161/mge.21617
Abstract | Full Text | PDF

MicroRNAs coordinate networks of mRNAs, but predicting specific sites of interactions is complicated by the very few bases of complementarity needed for regulation. Although efforts to characterize the specific requirements for microRNA (miR) regulation have made some advances, no general model of target recognition has been widely accepted. In this work, we describe an entirely novel approach to miR target identification. The genomic events responsible for the creation of individual miR loci have now been described with many miRs now known to have been initially formed from transposable element (TE) sequences. In light of this, we propose that limiting miR target searches to transcripts containing a miR’s progenitor TE can facilitate accurate target identification. In this report we outline the methodology behind OrbId (Origin-based identification of microRNA targets). In stark contrast to the principal miR target algorithms (which rely heavily on target site conservation across species and are therefore most effective at predicting targets for older miRs), we find OrbId is particularly efficacious at predicting the mRNA targets of miRs formed more recently in evolutionary time. After defining the TE origins of > 200 human miRs, OrbId successfully generated likely target sets for 191 predominately primate-specific human miR loci. While only a handful of the loci examined were well enough conserved to have been previously evaluated by existing algorithms, we find ~80% of the targets for the oldest miR (miR-28) in our analysis contained within the principal Diana and TargetScan prediction sets. More importantly, four of the 15 OrbId miR-28 putative targets have been previously verified experimentally. In light of OrbId proving best-suited for predicting targets for more recently formed miRs, we suggest OrbId makes a logical complement to existing, conservation based, miR target algorithms.




COMMENTARIES

Open Access Article

Algal genes in aplastidic eukaryotes are not necessarily derived from historical plastids

Jipei Yue and Jinling Huang
Pages 193 - 196
http://dx.doi.org/10.4161/mge.21745
Abstract | Full Text | PDF

In photosynthetic eukaryotes, many genes were transferred from plastids or algal endosymbionts to nuclear genomes of host cells. These transferred genes are often considered genetic footprints of plastids. However, genes of algal origin have also been detected in some plastid-lacking eukaryotes, and these genes are often cited as evidence of historical plastids. In this paper, we discuss two recent publications about algal genes in plastid-lacking eukaryotes. Both studies highlight the point that algal genes are not exclusively derived from historical plastids. Instead, the findings show that gene acquisition through feeding activities is a plausible explanation.

Open Access Article

Alu elements and human common diseases like obesity

Peter Kuehnen and Heiko Krude
Pages 197 - 201
http://dx.doi.org/10.4161/mge.21470
Abstract | Full Text | PDF

In the past few years the epigenetic impact on human diseases has been studied extensively. However, a controversial debate remains about the influence of environmental factors on the genetic determination of DNA methylation patterns. Although DNA methylation defects have been described in imprinting diseases and linked to cancer development, its impact on common diseases like obesity has yet to be elucidated. In our study we observed a hypermethylation variant of the POMC gene in obese children, which plays a key role in body weight regulation. Phylogenetic analyses reveal a close relationship between the POMC DNA methylation at this site and the presence of primate specific Alu elements. In this commentary we will extensively discuss our observations, including comments on the current debate about the impact of transposable elements on DNA methylation and on the development of human disease in general.