The piggyBac transposon holds promise for human gene therapy.
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Animals↗
Biomedical subjects
Cédric Feschotte
Publications and source records attributed to Cédric Feschotte.
Mavericks, a novel class of giant transposable elements widespread in eukaryotes and related to DNA viruses.
We previously identified a group of atypical mobile elements designated Mavericks from the nematodes Caenorhabditis elegans and C. briggsae and the zebrafish Danio rerio. Here we present the results of comprehensive database searches of the genome sequences available, which reveal that Mavericks are widespread in invertebrates and non-mammalian vertebrates but show a patchy distribution in non-animal species, being present in the fungi Glomus intraradices and Phakopsora pachyrhizi and in several single-celled eukaryotes such as the ciliate Tetrahymena thermophila, the stramenopile Phytophthora infestans and the trichomonad Trichomonas vaginalis, but not detectable in plants. This distribution, together with comparative and phylogenetic analyses of Maverick-encoded proteins, is suggestive of an ancient origin of these elements in eukaryotes followed by lineage-specific losses and/or recurrent episodes of horizontal transmission. In addition, we report that Maverick elements have amplified recently to high copy numbers in T. vaginalis where they now occupy as much as 30% of the genome. Sequence analysis confirms that most Mavericks encode a retroviral-like integrase, but lack other open reading frames typically found in retroelements. Nevertheless, the length and conservation of the target site duplication created upon Maverick insertion (5- or 6-bp) is consistent with a role of the integrase-like protein in the integration of a double-stranded DNA transposition intermediate. Mavericks also display long terminal-inverted repeats but do not contain ORFs similar to proteins encoded by DNA transposons. Instead, Mavericks encode a conserved set of 5 to 9 genes (in addition to the integrase) that are predicted to encode proteins with homology to replication and packaging proteins of some bacteriophages and diverse eukaryotic double-stranded DNA viruses, including a DNA polymerase B homolog and putative capsid proteins. Based on these and other structural similarities, we speculate that Mavericks represent an evolutionary missing link between seemingly disparate invasive DNA elements that include bacteriophages, adenoviruses and eukaryotic linear plasmids.
Amino Acid Sequence↗
Birth of a chimeric primate gene by capture of the transposase gene from a mobile element.
The emergence of new genes and functions is of central importance to the evolution of species. The contribution of various types of duplications to genetic innovation has been extensively investigated. Less understood is the creation of new genes by recycling of coding material from selfish mobile genetic elements. To investigate this process, we reconstructed the evolutionary history of SETMAR, a new primate chimeric gene resulting from fusion of a SET histone methyltransferase gene to the transposase gene of a mobile element. We show that the transposase gene was recruited as part of SETMAR 40-58 million years ago, after the insertion of an Hsmar1 transposon downstream of a preexisting SET gene, followed by the de novo exonization of previously noncoding sequence and the creation of a new intron. The original structure of the fusion gene is conserved in all anthropoid lineages, but only the N-terminal half of the transposase is evolving under strong purifying selection. In vitro assays show that this region contains a DNA-binding domain that has preserved its ancestral binding specificity for a 19-bp motif located within the terminal-inverted repeats of Hsmar1 transposons and their derivatives. The presence of these transposons in the human genome constitutes a potential reservoir of approximately 1,500 perfect or nearly perfect SETMAR-binding sites. Our results not only provide insight into the conditions required for a successful gene fusion, but they also suggest a mechanism by which the circuitry underlying complex regulatory networks may be rapidly established.
Amino Acid Sequence↗
Mobile DNA: genomes under the influence.
A report on the American Society for Microbiology Conference on Mobile DNA, Banff, Canada, 24 February-1 March 2006.
Animals↗
Unexpected diversity and differential success of DNA transposons in four species of entamoeba protozoans.
We report the first comprehensive analysis of transposable element content in the compact genomes (approximately 20 Mb) of four species of Entamoeba unicellular protozoans for which draft sequences are now available. Entamoeba histolytica and Entamoeba dispar, two human parasites, have many retrotransposons, but few DNA transposons. In contrast, the reptile parasite Entamoeba invadens and the free-living Entamoeba moshkovskii contain few long interspersed elements but harbor diverse and recently amplified populations of DNA transposons. Representatives of three DNA transposase superfamilies (hobo/Activator/Tam3, Mutator, and piggyBac) were identified for the first time in a protozoan species in addition to a variety of members of a fourth superfamily (Tc1/mariner), previously reported only from ciliates and Trichomonas vaginalis among protozoans. The diversity of DNA transposons and their differential amplification among closely related species with similar compact genomes are discussed in the context of the biology of Entamoeba protozoans.
Amino Acid Sequence↗
DNA-binding specificity of rice mariner-like transposases and interactions with Stowaway MITEs.
Mariner-like elements (MLEs) are DNA transposons found throughout the plant and animal kingdoms. A previous computational survey of the rice (Oryza sativa) genome sequence revealed 34 full length MLEs (Osmars) belonging to 25 distinct families. This survey, which also identified sequence similarities between the Osmar elements and the Stowaway superfamily of MITEs, led to the formulation of a hypothesis whereby Stowaways are mobilized by OSMAR transposases. Here we investigate the DNA-binding activities and specificities of two OSMAR transposases, OSMAR5 and OSMAR10. Like other mariner-like transposases, the OSMARs bind specifically to the terminal inverted repeat (TIR) sequences of their encoding transposons. OSMAR5 binds DNA through a bipartite N-terminal domain containing two functionally separable helix-turn-helix motifs, resembling the paired domain of Tc1-like transposases and PAX transcription factors in metazoans. Furthermore, binding of the OSMARs is not limited to their own TIRs; OSMAR5 transposase can also interact in vitro with TIRs from closely related Osmar elements and with consensus TIRs of several Stowaway families mined from the rice genome sequence. These results provide the first biochemical evidence for a functional relationship between Osmar elements and Stowaway MITEs and lead us to suggest that there is extensive cross-talk among related but distinct transposon families co-existing in a single eukaryote genome.
Base Sequence↗
Non-mammalian c-integrases are encoded by giant transposable elements.
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Animals↗
Merlin, a new superfamily of DNA transposons identified in diverse animal genomes and related to bacterial IS1016 insertion sequences.
Several new families of DNA transposons were identified by computer-assisted searches in a wide range of animal species that includes nematodes, flat worms, mosquitoes, sea squirt, zebrafish, and humans. Many of these elements have coding capacity for transposases, which are related to each other and to those encoded by the IS1016 group of bacterial insertion sequences. Although these transposases display a motif similar to the DDE motif found in many transposases and integrases, they cannot be directly allied to any of the previously described eukaryotic transposases. Other common features of the new eukaryotic and bacterial transposons include similarities in their terminal inverted repeats and 8-bp or 9-bp target-site duplications. Together, these data indicate that these elements belong to a new superfamily of DNA transposons, called Merlin/IS1016, which is common in many eubacterial and animal genomes. We also present evidence that these transposons have been recently active in several animal species. This evidence is particularly strong in the parasitic blood fluke Schistosoma mansoni, in which Merlin is also the first described DNA transposon family.
Animals↗
Using rice to understand the origin and amplification of miniature inverted repeat transposable elements (MITEs).
Recent studies of rice miniature inverted repeat transposable elements (MITEs), largely fueled by the availability of genomic sequence, have provided answers to many of the outstanding questions regarding the existence of active MITEs, their source of transposases (TPases) and their chromosomal distribution. Although many questions remain about MITE origins and mode of amplification, data accumulated over the past two years have led to the formulation of testable models.
DNA Transposable Elements↗
PIF- and Pong-like transposable elements: distribution, evolution and relationship with Tourist-like miniature inverted-repeat transposable elements.
Miniature inverted-repeat transposable elements (MITEs) are short, nonautonomous DNA elements that are widespread and abundant in plant genomes. Most of the hundreds of thousands of MITEs identified to date have been divided into two major groups on the basis of shared structural and sequence characteristics: Tourist-like and Stowaway-like. Since MITEs have no coding capacity, they must rely on transposases encoded by other elements. Two active transposons, the maize P Instability Factor (PIF) and the rice Pong element, have recently been implicated as sources of transposase for Tourist-like MITEs. Here we report that PIF- and Pong-like elements are widespread, diverse, and abundant in eukaryotes with hundreds of element-associated transposases found in a variety of plant, animal, and fungal genomes. The availability of virtually the entire rice genome sequence facilitated the identification of all the PIF/Pong-like elements in this organism and permitted a comprehensive analysis of their relationship with Tourist-like MITEs. Taken together, our results indicate that PIF and Pong are founding members of a large eukaryotic transposon superfamily and that members of this superfamily are responsible for the origin and amplification of Tourist-like MITEs.
Amino Acid Sequence↗
Genome-wide analysis of mariner-like transposable elements in rice reveals complex relationships with stowaway miniature inverted repeat transposable elements (MITEs).
Stowaway is a superfamily of miniature inverted repeat transposable elements (MITEs) that is widespread and abundant in plant genomes. Like other MITEs, however, its origin and mode of amplification are poorly understood. Several lines of evidence point to plant mariner-like elements (MLEs) as the autonomous partners of the nonautonomous Stowaway MITEs. To better understand this relationship, we have taken advantage of the nearly complete genome sequences of two rice subspecies to generate the first inventory of virtually all MLEs and Stowaway families coexisting in a single plant species. Thirty-four different MLEs were found to group into three major clades and 25 families. More than 22,000 Stowaway MITEs were identified and classified into 36 families. On the basis of detailed sequence comparisons, MLEs were confirmed to be the best candidate autonomous elements for Stowaway MITEs. Surprisingly, however, sequence similarity between MLE and Stowaway families was restricted to the terminal inverted repeats (TIRs) and, in a few cases, to adjacent subterminal sequences. These data suggest a model whereby most of the Stowaway MITEs in rice were cross-mobilized by MLE transposases encoded by distantly related elements.
Base Sequence↗
An Ac-like transposable element family with transcriptionally active Y-linked copies in the white campion, Silene latifolia.
An RFLP genomic subtraction was used to isolate male-specific sequences in the species Silene latifolia. One isolated fragment, SLP2, shares similarity to a portion of the Activator (Ac) transposase from Zea mays and to related proteins from other plant species. Southern blot analysis of male and female S. latifolia genomic DNA shows that SLP2 belongs to a low-copy-number repeat family with two Y-linked copies. Screening of a S. latifolia male genomic library using SLP2 as a probe led to the isolation of five clones, which were partially sequenced. One clone contains two large open reading frames that can be joined into a sequence encoding a putative protein of 682 amino acids by removing a short intron. Database searches and phylogenetic analysis show that this protein belongs to the hAT superfamily of transposases, closest to Tag2 (Arabidopsis thaliana), and contains all of the defined domains critical for the activity of these transposases. PCR with genomic and cDNA templates from S. latifolia male, female, and hermaphrodite individuals revealed that one of the Y-linked copies is transcriptionally active and alternatively spliced. This is the first report of a transcriptionally active transposable element (TE) family in S. latifolia and the first DNA transposon residing on a plant Y chromosome. The potential activity and regulation of this TE family and its use for Y chromosome gene discovery is discussed.
Amino Acid Sequence↗
Plant transposable elements: where genetics meets genomics.
Transposable elements are the single largest component of the genetic material of most eukaryotes. The recent availability of large quantities of genomic sequence has led to a shift from the genetic characterization of single elements to genome-wide analysis of enormous transposable-element populations. Nowhere is this shift more evident than in plants, in which transposable elements were first discovered and where they are still actively reshaping genomes.
DNA Methylation↗
Mariner-like transposases are widespread and diverse in flowering plants.
Complete and partial sequences of mariner-like elements (MLEs) have been reported for hundreds of species of animals, but only two have been identified in plants. On the basis of these two plant MLEs and several related sequences identified by database searches, plant-specific degenerate primers were derived and used to amplify a conserved region of MLE transposase genes from a variety of plant genomes. Positive products were obtained for 6 dicots and 31 monocots of 54 plant species tested. Phylogenetic analysis of 68 distinct MLE transposase sequences from 25 grass species is consistent with vertical transmission and rapid diversification of multiple lineages of transposases. Surprisingly, the evolution of MLEs in grasses was accompanied by repeated and independent acquisition of introns in a localized region of the transposase gene.
DNA-Binding Proteins↗