Table of Contents

Volume 2, Issue 1

  January/February 2012

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LETTERS TO THE EDITOR

Open Access Article

Pr77 and L1TcRz: A dual system within the 5′-end of L1Tc retrotransposon, internal promoter and HDV-like ribozyme

Francisco Sánchez-Luque, Manuel C. López, Francisco Macias, Carlos Alonso and M. Carmen Thomas
Abstract | Full Text | PDF

The sequence corresponding to the first 77 nucleotides of the L1Tc and NARTc non-LTR retrotransposons from Trypanosoma cruzi is an internal promoter (Pr77) that generates abundant, although poorly translatable, un-spliced transcripts. It has been recently described that L1TcRz, an HDV-like ribozyme, resides within the 5′-end of the RNA from the L1Tc and NARTc retrotransposons. Remarkably, the same first 77 nucleotides of L1Tc/NARTc elements comprise both the Pr77 internal promoter and the HDV-like L1TcRz. The L1TcRz cleaves on the 5′-side of the +1 nucleotide of the L1Tc element insuring that the promoter and the ribozyme functions travel with the transposon during retrotransposition. The ribozyme activity would prevent the mobilization of upstream sequences and insure the individuality of the L1Tc/NARTc copies transcribed from associated tandems. The Pr77/L1TcRz sequence is also found in other trypanosomatid’s non-LTR retrotransposons and degenerated retroposons. The possible conservation of the ribozyme activity in a widely degenerated retrotransposon, as the Leishmania SIDERs, could indicate that the presence of this element and the catalytic activity could play some favorable genetic regulation. The functional implications of the Pr77/L1TcRz dual system in the regulation of the L1Tc/NARTc retrotransposons and in the gene expression of trypanosomatids are also discussed in this paper.

Open Access Article

In silico analysis of sequenced strains of Clostridium difficile reveals a related set of conjugative transposons carrying a variety of accessory genes

Michael S.M. Brouwer, Adam P. Roberts, Peter Mullany and Elaine Allan
Abstract | Full Text | PDF

The human gut pathogen Clostridium difficile contains many conjugative transposons that have an array of accessory genes. In the current study, recently sequenced genomes were analyzed to identify new putative conjugative transposons. Eleven new elements in 5 C. difficile strains were identified and all had a similar structure to the previously described elements CTn1, CTn5 and CTn7 in C. difficile strain 630. Each element identified did however contain a new set of accessory genes compared with those previously reported; including those predicted to encode ABC transporters, a toxin / antitoxin system and multiple antibiotic resistance genes.

Open Access Article

Integron associated mobile genes: Just a collection of plug in apps or essential components of cell network hardware?

Maurizio Labbate, Yan Boucher, Ivan Luu, Piklu Roy Chowdhury and H. W. Stokes
Abstract | Full Text | PDF

Lateral Gene Transfer (LGT) impacts on the evolution of prokaryotes in both the short and long-term. The short-term impacts of mobilized genes are a concern to humans since LGT explains the global rise of multi drug resistant pathogens seen in the past 70 y. However, LGT has been a feature of prokaryotes from the earliest days of their existence and the concept of a bifurcating tree of life is not entirely applicable to prokaryotes since most genes in extant prokaryotic genomes have probably been acquired from other lineages. Successful transfer and maintenance of a gene in a new host is understandable if it acts independently of cell networks and confers an advantage. Antibiotic resistance provides an example of this whereby a gene can be advantageous in virtually any cell across broad species backgrounds. In a longer evolutionary context however laterally transferred genes can be assimilated into even essential cell networks. How this happens is not well understood and we discuss recent work that identifies a mobile gene, unique to a cell lineage, which is detrimental to the cell when lost. We also present some additional data and believe our emerging model will be helpful in understanding how mobile genes integrate into cell networks.




RESEARCH PAPERS

Open Access Article

Do human transposable element small RNAs serve primarily as genome defenders or genome regulators?

Kevin Lee, Andrew Conley, Victoria V. Lunyak and I. King Jordan
Abstract | Full Text | PDF

It is currently thought that small RNA (sRNA) based repression mechanisms are primarily employed to mitigate the mutagenic threat posed by the activity of transposable elements (TEs). This can be achieved by the sRNA guided processing of TE transcripts via Dicer-dependent (e.g., siRNA) or Dicer-independent (e.g., piRNA) mechanisms. For example, potentially active human L1 elements are silenced by mRNA cleavage induced by element encoded siRNAs, leading to a negative correlation between element mRNA and siRNA levels. On the other hand, there is emerging evidence that TE derived sRNAs can also be used to regulate the host genome. Here, we evaluated these two hypotheses for human TEs by comparing the levels of TE derived mRNA and TE sRNA across six tissues. The genome defense hypothesis predicts a negative correlation between TE mRNA and TE sRNA levels, whereas the genome regulatory hypothesis predicts a positive correlation. On average, TE mRNA and TE sRNA levels are positively correlated across human tissues. These correlations are higher than seen for human genes or for randomly permuted control data sets. Overall, Alu subfamilies show the highest positive correlations of element mRNA and sRNA levels across tissues, although a few of the youngest, and potentially most active, Alu subfamilies do show negative correlations. Thus, Alu derived sRNAs may be related to both genome regulation and genome defense. These results are inconsistent with a simple model whereby TE derived sRNAs reduce levels of standing TE mRNA via transcript cleavage, and suggest that human cells efficiently process TE transcripts into sRNA based on the available message levels. This may point to a widespread role for processed TE transcripts in genome regulation or to alternative roles of TE-to-sRNA processing including the mitigation of TE transcript cytotoxicity.

Open Access Article

Protein interactions with piALU RNA indicates putative participation of retroRNA in the cell cycle, DNA repair and chromatin assembly

Benjamin Blackwell, Mary F. Lopez, Jianrong Wang, Bryan Krastins, David Sarracino, James R. Tollervey, Marek Dobke, I. King Jordan and Victoria V. Lunyak
Abstract | Full Text | PDF

Recent analyses suggest that transposable element-derived transcripts are processed to yield a variety of small RNA species that play critical functional roles in gene regulation and chromatin organization as well as genome stability and maintenance. Here we report a mass spectrometry analysis of an RNA-affinity complex isolation using a piRNA homologous sequence derived from Alu retrotransposal RNA. Our data point to potential roles for piALU RNAs in DNA repair, cell cycle and chromatin regulations.




REVIEW

Open Access Article

Drosophila Errantiviruses

Yury Stefanov, Veniamin Salenko and Ivan Glukhov
Abstract | Full Text | PDF

Retroelements with long-terminal repeats (LTRs) inhabit nearly all eukaryotic genomes. During the time of their rich evolutionary history they have developed highly diverse forms, ranging from ordinary retrotransposons to complex pathogenic retroviruses such as HIV-I. Errantiviruses are a group of insect endogenous LTR elements that share structural and functional features with vertebrate endogenous retroviruses. The errantiviruses illustrate one of the evolutionary strategies of retrotransposons to become infective, which together with their similarities to vertebrate retroviruses make them an attractive object of research promising to shed more light on the evolution of retroviruses.




COMMENTARIES

Open Access Article

Order in the playground: Formation of plant gene clusters in dynamic chromosomal regions

Ben Field and Anne Osbourn
Abstract | Full Text | PDF

In eukaryotes the arrangement of genes along the chromosome is not as random as it at first appeared, and distinctive clusters of functionally related but non-homologous genes can be found in the genomes of certain animals and fungi. These include the major histocompatibility complex in mammals and gene clusters for nutrient use and secondary metabolite production in fungi. A growing number of functional gene clusters for different types of secondary metabolite are now being discovered in plant genomes. However, the molecular mechanisms and evolutionary pressures behind their formation are poorly understood. Here we discuss the implications of our recent investigation into the origin of two functional gene clusters in the model plant Arabidopsis thaliana.

Open Access Article

A proposal for the reference-based annotation of de novo transposable element insertions

Casey M. Bergman
Abstract | Full Text | PDF

Understanding the causes and consequences of transposable element (TE) activity in the genomic era requires sophisticated bioinformatics approaches to accurately identify individual insertion sites. Next-generation sequencing technology now makes it possible to rapidly identify new TE insertions using resequencing data, opening up new possibilities to study the nature of TE-induced mutation and the target site preferences of different TE families. While the identification of new TE insertion sites is seemingly a simple task, the mechanisms of transposition present unique challenges for the annotation of de novo transposable element insertions mapped to a reference genome. Here I discuss these challenges and propose a framework for the annotation of de novo TE insertions that accommodates known mechanisms of TE insertion and established coordinate systems for genome annotation.

Open Access Article

IncA/C plasmids: An emerging threat to human and animal health?

Timothy Johnson and Kevin Lang
Abstract | Full Text | PDF

Incompatibility group IncA/C plasmids are large, low copy, theta-replicating plasmids that have been described in the literature for over 40 y. However, they have only recently been intensively studied on the genomic level because of their associations with the emergence of multidrug resistance in enteric pathogens of humans and animals. These plasmids are unique among other enterobacterial plasmids in many aspects, including their modular structure and gene content. While the IncA/C plasmid genome structure has now been well defined, many questions remain pertaining to their basic biological mechanisms of dissemination and regulation. Here, we discuss the history of IncA/C plasmids in light of our recent understanding of their population distribution, genomics, and effects on host bacteria.

Open Access Article

Phylogenomic approaches underestimate eukaryotic gene transfer

Jan Andersson
Abstract | Full Text | PDF

Phylogenomic approaches have shown that eukaryotes acquire genes via gene transfer. However, there are two fundamental problems for most of these analyses; only transfers from prokaryotes are analyzed and the screening procedures applied assume that gene transfer is rare for eukaryotes. Directed studies of the impact of gene transfer on diverse eukaryotic lineages produce a much more complex picture. Many gene families are affected by multiple transfer events from prokaryotes to eukaryotes, and transfers between eukaryotic lineages are routinely detected. This suggests that the assumptions applied in traditional phylogenomic approaches are too naïve and result in many false negatives. This issue was recently addressed by identifying and analyzing the evolutionary history of 49 patchily distributed proteins shared between Dictyostelium and bacteria. The vast majority of these gene families showed strong indications of gene transfers, both between and within the three domains of life. However, only one of these was previously reported as a gene transfer candidate using a traditional phylogenomic approach. This clearly illustrates that more realistic assumptions are urgently needed in genome-wide studies of eukaryotic gene transfer.

Open Access Article

CRISPR/Cas systems in archaea: What array spacers can teach us about parasitism and gene exchange in the 3rd domain of life

Uri Gophna and Avital Brodt
Abstract | Full Text | PDF

CRISPR (Clustered, Regularly, Interspaced, Short, Palindromic Repeats) loci have been shown to provide prokaryotes with an adaptive immunity against viruses and plasmids. CRISPR arrays are transcribed and processed into small CRISPR RNA molecules, which base-pair with invading DNA or RNA and lead to its degradation by CRISPR-associated (Cas) protein complexes. New spacers can be acquired by active CRISPR/Cas systems, and thus the sequences of these spacers provide a record of the past “infection history” of the organism. Recently we used spacer sequences from archaeal genomes to infer gene exchange events among archaeal species and genera and to demonstrate that at least in this domain of life CRISPR indeed has an anti-viral role.