Whole Genome Resequencing Reveals Natural Target Site Preferences of Transposable Elements in Drosophila melanogaster

Linheiro, Raquel; Bergman, Casey M.

doi:10.1371/journal.pone.0030008

Cited by 125 publications

(144 citation statements)

References 61 publications

Supporting

Mentioning

129

Contrasting

Order By: Relevance

“…2). A feature of Roo TEs is insertion site duplication, where 5 bp of genomic DNA is duplicated at either side of the point where the TE inserts (28). When ectopic recombination occurs between two different TE insertions, the flanking sequences should differ on each side of the TE.…”

Section: Resultsmentioning

confidence: 99%

Gene duplication in the major insecticide target site,Rdl, inDrosophila melanogaster

Remnant

Good

Schmidt

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The Resistance to Dieldrin gene, Rdl, encodes a GABA-gated chloride channel subunit that is targeted by cyclodiene and phenylpyrazole insecticides. The gene was first characterized in Drosophila melanogaster by genetic mapping of resistance to the cyclodiene dieldrin. The 4,000-fold resistance observed was due to a single amino acid replacement, Ala 301 to Ser. The equivalent change was subsequently identified in Rdl orthologs of a large range of resistant insect species. Here, we report identification of a duplication at the Rdl locus in D. melanogaster. The 113-kb duplication contains one WT copy of Rdl and a second copy with two point mutations: an Ala 301 to Ser resistance mutation and Met 360 to Ile replacement. Individuals with this duplication exhibit intermediate dieldrin resistance compared with single copy Ser 301 homozygotes, reduced temperature sensitivity, and altered RNA editing associated with the resistant allele. Ectopic recombination between Roo transposable elements is involved in generating this genomic rearrangement. The duplication phenotypes were confirmed by construction of a transgenic, artificial duplication integrating the 55.7-kb Rdl locus with a Ser 301 change into an Ala 301 background. Gene duplications can contribute significantly to the evolution of insecticide resistance, most commonly by increasing the amount of gene product produced. Here however, duplication of the Rdl target site creates permanent heterozygosity, providing unique potential for adaptive mutations to accrue in one copy, without abolishing the endogenous role of an essential gene.T he single point mutation in the Resistance to dieldrin (Rdl) gene represents one of the most significant cases of target site resistance to an insecticide yet observed. Cyclodiene resistance was reported in 62% of insecticide resistant species in the 1980s, following widespread use of cyclodiene insecticides, including dieldrin, which started in the 1950s (1). The nature of the genetic target, Rdl, was discovered after dieldrin was discontinued because of the widespread evolution of resistance in many species. Rdl was first discovered in Drosophila melanogaster using a positional cloning approach. High homology to human GABA receptors confirmed it was the first insect ligand-gated chloride channel subunit identified (2-4). A point mutation in the chloride channel pore-lining domain, replacing alanine 301 with serine, was present in all resistant D. melanogaster strains (5). This mutation provided 4,000-fold resistance when homozygous and lower levels of resistance in heterozygotes (2, 6). The homologous mutation was subsequently found in a large number of cyclodiene-resistant species from many insect orders (7-9), as well as a glycine replacement at the homologous site in some resistant strains of Drosophila simulans and other species (5, 10, 11).Characterization of deficiency lines and inversions in D. melanogaster showed that Rdl is an essential gene (3). Thus, the Ala 301 to Ser or Gly mutation in Rdl exhibits unique properties, p...

show abstract

Section: Resultsmentioning

confidence: 99%

Gene duplication in the major insecticide target site,Rdl, inDrosophila melanogaster

Remnant

Good

Schmidt

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…We determined the size of the retroposed sequences, of the replaced regions of the LTR retrotransposons, and of the microsimilarities following the distributions learned from the empirical set of 15 retrocopies. We simulated non-LTR-mediated retrocopies with 5 ′ truncation (≤500 bp), poly(A) tails (≤100 bp), and TSD (≤10 bp) based on previous studies (Linheiro and Bergman 2012;Subtelny et al 2014). We randomly inserted the simulated retrocopies into intergenic or intronic regions.…”

Section: Evaluation Of Potential Bias In the Detection Of Ltr-mediatementioning

confidence: 99%

LTR-mediated retroposition as a mechanism of RNA-based duplication in metazoans

et al. 2016

View full text Add to dashboard Cite

In a broad range of taxa, genes can duplicate through an RNA intermediate in a process mediated by retrotransposons (retroposition). In mammals, L1 retrotransposons drive retroposition, but the elements responsible for retroposition in other animals have yet to be identified. Here, we examined young retrocopies from various animals that still retain the sequence features indicative of the underlying retroposition mechanism. In Drosophila melanogaster, we identified and de novo assembled 15 polymorphic retrocopies and found that all retroposed loci are chimeras of internal retrocopies flanked by discontinuous LTR retrotransposons. At the fusion points between the mRNAs and the LTR retrotransposons, we identified shared short similar sequences that suggest the involvement of microsimilarity-dependent template switches. By expanding our approach to mosquito, zebrafish, chicken, and mammals, we identified in all these species recently originated retrocopies with a similar chimeric structure and shared microsimilarities at the fusion points. We also identified several retrocopies that combine the sequences of two or more parental genes, demonstrating LTR-retroposition as a novel mechanism of exon shuffling. Finally, we found that LTR-mediated retrocopies are immediately cotranscribed with their flanking LTR retrotransposons. Transcriptional profiling coupled with sequence analyses revealed that the sense-strand transcription of the retrocopies often lead to the origination of in-frame proteins relative to the parental genes. Overall, our data show that LTR-mediated retroposition is highly conserved across a wide range of animal taxa; combined with previous work from plants and yeast, it represents an ancient and ongoing mechanism continuously shaping gene content evolution in eukaryotes.

show abstract

“…Other RNase H-like transposases have preferred sites of integration. These involve distinct and often palindromic (127) patterns of base pairs (128)(129)(130)(131)(132)(133)(134)(135)(136)(137), suggesting that these target site preferences might reflect some other property other than sequence specificity, for example perhaps DNA bendability. Indeed, target DNA has been repeatedly observed to be bent when bound by transpososomes (e.g., for Tn7 (138), Tn10 (139), Mos1 (140), MuA (93)), and such bending has been proposed to be an effective mechanism to ensure the directionality of the reaction (93,141).…”

Section: (Iv) Target Binding and Integrationmentioning

confidence: 99%

Mechanisms of DNA Transposition

Hickman

Dyda

2015

Microbiol Spectr

View full text Add to dashboard Cite

DNA transposases use a limited repertoire of structurally and mechanistically distinct nuclease domains to catalyze the DNA strand breaking and rejoining reactions that comprise DNA transposition. Here, we review the mechanisms of the four known types of transposition reactions catalyzed by (1) RNase H-like transposases (also known as DD(E/D) enzymes); (2) HUH single-stranded DNA transposases; (3) serine transposases; and (4) tyrosine transposases. The large body of accumulated biochemical and structural data, particularly for the RNase H-like transposases, has revealed not only the distinguishing features of each transposon family, but also some emerging themes that appear conserved across all families. The more-recently characterized single-stranded DNA transposases provide insight into how an ancient HUH domain fold has been adapted for transposition to accomplish excision and then site-specific integration. The serine and tyrosine transposases are structurally and mechanistically related to their cousins, the serine and tyrosine site-specific recombinases, but have to date been less intensively studied. These types of enzymes are particularly intriguing as in the context of site-specific recombination they require strict homology between recombining sites, yet for transposition can catalyze the joining of transposon ends to form an excised circle and then integration into a genomic site with much relaxed sequence specificity.In this chapter, we provide an overview of the fundamental concepts of DNA transposition mechanisms. Our aim is to emphasize basic themes and, in this effort, we will focus on specific illustrative cases rather than attempt an exhaustive review of the literature. We hope that the selected references will point the curious reader towards the landmark studies in the field as well as some of the most exciting recent results. We also direct the reader to other recent reviews (1-3).DNA transposases are enyzmes that move discrete segments of DNA called transposons from one location in the genome (often called the donor site) to a new site without using RNA intermediates. DNA transposases are usually encoded by the mobile element itself (in which case they are "autonomous" transposons). However, some transposons are missing a self-encoded transposase yet have ends that can be recognized by a transposase encoded somewhere else in the genome, and thus are "non-autonomous" (Siguier et al., this volume). Although logic suggests that all DNA transposons are moved by transposases, the term was originally reserved for those enzymes that do not require significant regions of homology between any part of the transposon and the sites to which they are moved, the so-called target (or insertion or integration) sites. As biology is not always neat and tidy, transposases can exhibit a spectrum of homology requirements and vagaries of terminology have arisen such that certain transposases are sometimes referred to as "resolvases" or by the generic term "recombinases".From a mechanistic perspective, t...

show abstract

Whole Genome Resequencing Reveals Natural Target Site Preferences of Transposable Elements in Drosophila melanogaster

Cited by 125 publications

References 61 publications

Gene duplication in the major insecticide target site,Rdl, inDrosophila melanogaster

Gene duplication in the major insecticide target site,Rdl, inDrosophila melanogaster

LTR-mediated retroposition as a mechanism of RNA-based duplication in metazoans

Mechanisms of DNA Transposition

Contact Info

Product

Resources

About