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Transposable element
Transposable element
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A bacterial DNA transposon

A transposable element (TE), also transposon, or jumping gene, is a type of mobile genetic element, a nucleic acid sequence in DNA that can change its position within a genome.

The discovery of mobile genetic elements earned Barbara McClintock a Nobel Prize in 1983.[1]

TEs are very common in nature, especially in plants and animals. About 50% of the maize genome, for instance, is made up by TEs.[2]

There are at least[further explanation needed] two classes of TEs: Class I TEs or retrotransposons generally function via reverse transcription, while Class II TEs or DNA transposons encode the protein transposase, which they require for insertion and excision, and some of these TEs also encode other proteins.[3]

Discovery by Barbara McClintock

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Barbara McClintock discovered the first TEs in maize (Zea mays) at the Cold Spring Harbor Laboratory in New York. McClintock was experimenting with maize plants that had broken chromosomes.[4]

In the winter of 1944–1945, McClintock planted corn kernels that were self-pollinated, meaning that the silk (style) of the flower received pollen from its own anther.[4] These kernels came from a long line of plants that had been self-pollinated, causing broken arms on the end of their ninth chromosomes.[4] As the maize plants began to grow, McClintock noted unusual color patterns on the leaves.[4] For example, one leaf had two albino patches of almost identical size, located side by side on the leaf.[4] McClintock hypothesized that during cell division certain cells lost genetic material, while others gained what they had lost.[5] However, when comparing the chromosomes of the current generation of plants with the parent generation, she found certain parts of the chromosome had switched position.[5] This refuted the popular genetic theory of the time that genes were fixed in their position on a chromosome. McClintock found that genes could not only move but they could also be turned on or off due to certain environmental conditions or during different stages of cell development.[5]

McClintock also showed that gene mutations could be reversed.[6] She presented her report on her findings in 1951, and published an article on her discoveries in Genetics in November 1953 entitled "Induction of Instability at Selected Loci in Maize".[7]

At the 1951 Cold Spring Harbor Symposium where she first publicized her findings, her talk was met with silence.[8] Her work was largely dismissed and ignored until the late 1960s–1970s when, after TEs were found in bacteria, it was rediscovered.[9] She was awarded a Nobel Prize in Physiology or Medicine in 1983 for her discovery of TEs, more than thirty years after her initial research.[10]

Classification

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Transposable elements represent one of several types of mobile genetic elements. TEs are assigned to one of two classes according to their mechanism of transposition, which can be described as either copy and paste (Class I TEs) or cut and paste (Class II TEs).[11]

Class I: Retrotransposon

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Main article: Retrotransposon

Class I TEs are copied in two stages: first, they are transcribed from DNA to RNA, and the RNA produced is then reverse transcribed to DNA. This copied DNA is then inserted back into the genome at a new position. The reverse transcription step is catalyzed by a reverse transcriptase, which is often encoded by the TE itself. The characteristics of retrotransposons are similar to retroviruses, such as HIV.

Despite the potential negative effects of retrotransposons, like inserting itself into the middle of a necessary DNA sequence, which can render important genes unusable, they are still essential to keep a species' ribosomal DNA (rDNA) intact over the generations, preventing infertility.[12] The R2 retrotransposon of Drosophila creates double-stranded breaks by endonuclease activity during its process of replication within its target rDNA, allowing for homologous recombination between sister chromatids to repair the breaks.[13][14] The resulting chromatids, each with different quantities of rDNA, are tagged and differentially segregated during asymmetric division of progenitors into daughter stem cells, which receive the chromatids with more rDNA, and germ cell precursors.[15]

Retrotransposons are commonly grouped into three main orders:

Retroviruses can also be considered TEs. For example, after the conversion of retroviral RNA into DNA inside a host cell, the newly produced retroviral DNA is integrated into the genome of the host cell. These integrated DNAs are termed proviruses. The provirus is a specialized form of eukaryotic retrotransposon, which can produce RNA intermediates that may leave the host cell and infect other cells. The transposition cycle of retroviruses has similarities to that of prokaryotic TEs, suggesting a distant relationship between the two.

Class II: DNA transposons

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Main article: DNA transposon
A. Structure of DNA transposons (Mariner type). Two inverted tandem repeats (TIR) flank the transposase gene. Two short tandem site duplications (TSD) are present on both sides of the insert.
B. Mechanism of transposition: Two transposases recognize and bind to TIR sequences, join and promote DNA double-strand cleavage. The DNA-transposase complex then inserts its DNA cargo at specific DNA motifs elsewhere in the genome, creating short TSDs upon integration.[16]

The cut-and-paste transposition mechanism of class II TEs does not involve an RNA intermediate. The transpositions are catalyzed by several transposase enzymes. Some transposases non-specifically bind to any target site in DNA, whereas others bind to specific target sequences. The transposase makes a staggered cut at the target site producing sticky ends, cuts out the DNA transposon and ligates it into the target site. A DNA polymerase fills in the resulting gaps from the sticky ends and DNA ligase closes the sugar-phosphate backbone. This results in target site duplication and the insertion sites of DNA transposons may be identified by short direct repeats (a staggered cut in the target DNA filled by DNA polymerase) followed by inverted repeats (which are important for the TE excision by transposase).

Cut-and-paste TEs may be duplicated if their transposition takes place during S phase of the cell cycle, when a donor site has already been replicated but a target site has not yet been replicated.[citation needed] Such duplications at the target site can result in gene duplication, which plays an important role in genomic evolution.[17]: 284 

Not all DNA transposons transpose through the cut-and-paste mechanism. In some cases, a replicative transposition is observed in which a transposon replicates itself to a new target site (e.g. helitron).

Class II TEs comprise less than 2% of the human genome, making the rest Class I.[18]

Autonomous and non-autonomous

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Transposition can be classified as either "autonomous" or "non-autonomous" in both Class I and Class II TEs. Autonomous TEs can move by themselves, whereas non-autonomous TEs require the presence of another TE to move. This is often because dependent TEs lack transposase (for Class II) or reverse transcriptase (for Class I).

Activator element (Ac) is an example of an autonomous TE, and dissociation elements (Ds) is an example of a non-autonomous TE. Without Ac, Ds is not able to transpose.

Class III

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Some researchers also identify a third class of transposable elements,[19] which has been described as "a grab-bag consisting of transposons that don't clearly fit into the other two categories".[20] Examples of such TEs are the Foldback (FB) elements of Drosophila melanogaster, the TU elements of Strongylocentrotus purpuratus, and Miniature Inverted-repeat Transposable Elements.[21][22]

Locations in genomes

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Transposable elements can be all over a genome, as in the case of maize, in which TEs make up 50% of the genome.[2] In yeast (which has 5 classes of retrotransposons, Ty1-Ty5), over 90% of the Ty1 through T4 elements are located within 750 bp upstream of genes transcribed by RNA polymerase III, particularly tRNA genes. The Ty5 elements are all located at the telomeres or regions with telomeric chromatin.[2]

Negative effects

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Transposons can damage the genome of their host cell in different ways:

  • A transposon can insert into a functional gene and disable that gene.
  • After a DNA transposon is excised, the resulting gap may not be repaired correctly.
  • Many TEs contain promoters that drive transcription of their own genes. These promoters can cause aberrant expression of linked genes.

Diseases

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Diseases often caused by TEs include

  • Hemophilia A and B
    • LINE1 (L1) TEs that land on the human Factor VIII have been shown to cause haemophilia[23]
  • Severe combined immunodeficiency
    • Insertion of L1 into the APC gene causes colon cancer, confirming that TEs play an important role in disease development.[24]
  • Porphyria
    • Insertion of Alu element into the PBGD gene leads to interference with the coding region and leads to acute intermittent porphyria[25] (AIP).
  • Predisposition to cancer
    • LINE1(L1) TE's and other retrotransposons have been linked to cancer because they cause genomic instability.[23]
  • Duchenne muscular dystrophy.[26][27]
    • Caused by SVA transposable element insertion in the fukutin (FKTN) gene which renders the gene inactive.[23]
  • Alzheimer's Disease and other Tauopathies
    • Transposable element dysregulation can cause neuronal death, leading to neurodegenerative disorders[28]

Rate of transposition, induction and defense

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One study estimated the rate of transposition of a particular retrotransposon, the Ty1 element in Saccharomyces cerevisiae. Using several assumptions, the rate of successful transposition event per single Ty1 element came out to be about once every few months to once every few years.[29] Some TEs contain heat-shock like promoters and their rate of transposition increases if the cell is subjected to stress,[30] thus increasing the mutation rate under these conditions, which might be beneficial to the cell.

Cells defend against the proliferation of TEs in a number of ways. These include piRNAs and siRNAs,[31] which silence TEs after they have been transcribed.

If organisms are mostly composed of TEs, one might assume that disease caused by misplaced TEs is very common, but in most cases TEs are silenced through epigenetic mechanisms like DNA methylation, chromatin remodeling and piRNA, such that little to no phenotypic effects nor movements of TEs occur as in some wild-type plant TEs. Certain mutated plants have been found to have defects in methylation-related enzymes (methyl transferase) which cause the transcription of TEs, thus affecting the phenotype.[3][32]

One hypothesis suggests that only approximately 100 LINE1 related sequences are active, despite their sequences making up 17% of the human genome. In human cells, silencing of LINE1 sequences is triggered by an RNA interference (RNAi) mechanism. Surprisingly, the RNAi sequences are derived from the 5′ untranslated region (UTR) of the LINE1, a long terminal which repeats itself. Supposedly, the 5′ LINE1 UTR that codes for the sense promoter for LINE1 transcription also encodes the antisense promoter for the miRNA that becomes the substrate for siRNA production. Inhibition of the RNAi silencing mechanism in this region showed an increase in LINE1 transcription.[3][33]

Evolution

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TEs are found in almost all life forms, and the scientific community is still exploring their evolution and their effect on genome evolution. It is unclear whether TEs originated in the last universal common ancestor, arose independently multiple times, or arose once and then spread to other kingdoms by horizontal gene transfer.[34]

Because excessive TE activity can damage exons, many organisms have acquired mechanisms to inhibit their activity. Bacteria may undergo high rates of gene deletion as part of a mechanism to remove TEs and viruses from their genomes, while eukaryotic organisms typically use RNA interference to inhibit TE activity. Nevertheless, some TEs generate large families often associated with speciation events.[35] Evolution often deactivates DNA transposons, leaving them as introns (inactive gene sequences). In vertebrate animal cells, nearly all 100,000+ DNA transposons per genome have genes that encode inactive transposase polypeptides.[36]

Sleeping Beauty/Tc1/mariner. The first synthetic transposon designed for use in vertebrate (including human) cells, the Sleeping Beauty transposon system, is a Tc1/mariner-like transposon. Its dead ("fossil") versions are spread widely in the salmonid genome and a functional version was engineered by comparing those versions.[37] Human Tc1-like transposons are divided into Hsmar1 and Hsmar2 subfamilies. Although both types are inactive, one copy of Hsmar1 found in the SETMAR gene is under selection as it provides DNA-binding for the histone-modifying protein.[38] Many other human genes are similarly derived from transposons.[39] Hsmar2 has been reconstructed multiple times from the fossil sequences.[40]

Selective advantages. TEs may affect gene regulatory networks and thus have evolutionary advantages.[41] Interspersed repeats are created by transposition; since they can inhibit gene conversion, they protect novel gene sequences from being overwritten by similar gene sequences and thereby facilitate the development of new genes. TEs may also have been co-opted by the vertebrate immune system as a means of producing antibody diversity. The V(D)J recombination system operates by a mechanism similar to that of some TEs. TEs also serve to generate repeating sequences that can form dsRNA to act as a substrate for the action of ADAR in RNA editing.[42]

TEs can contain many types of genes, including those conferring antibiotic resistance and the ability to transpose to conjugative plasmids. Some TEs also contain integrons, genetic elements that can capture and express genes from other sources. These contain integrase, which can integrate gene cassettes. There are over 40 antibiotic resistance genes identified on cassettes, as well as virulence genes.[citation needed]

Novel genes and exon shuffling. Transposons do not always excise their elements precisely, sometimes removing the adjacent base pairs; this can lead to merged exons in a process called exon shuffling. Shuffling two unrelated exons can create a novel gene product or, more likely, an intron.[43]

Some non-autonomous DNA TEs found in plants can capture coding DNA from genes and shuffle them across the genome.[44] This process can duplicate genes in the genome (a phenomenon called transduplication), and can contribute to generate novel genes by exon shuffling.[45]

Evolutionary drive for TEs on the genomic context

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There is a hypothesis that states that TEs might provide a ready source of DNA that could be co-opted by the cell to help regulate gene expression. Research showed that many diverse modes of TEs co-evolution along with some transcription factors targeting TE-associated genomic elements and chromatin are evolving from TE sequences. Most of the time, these particular modes do not follow the simple model of TEs and regulating host gene expression.[46]

De novo repeat identification

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De novo repeat identification is an initial scan of sequence data that seeks to find the repetitive regions of the genome, and to classify these repeats. Many computer programs exist to perform de novo repeat identification, all operating under the same general principles.[47] As short tandem repeats are generally 1–6 base pairs in length and are often consecutive, their identification is relatively simple.[48] Dispersed repetitive elements, on the other hand, are more challenging to identify, due to the fact that they are longer and have often acquired mutations. However, it is important to identify these repeats as they are often found to be transposable elements (TEs).[47]

De novo identification of transposons involves three steps: 1) find all repeats within the genome, 2) build a consensus of each family of sequences, and 3) classify these repeats. There are three groups of algorithms for the first step. One group is referred to as the k-mer approach, where a k-mer is a sequence of length k. In this approach, the genome is scanned for overrepresented k-mers; that is, k-mers that occur more often than is likely based on probability alone. The length k is determined by the type of transposon being searched for. The k-mer approach also allows mismatches, the number of which is determined by the analyst. Some k-mer approach programs use the k-mer as a base, and extend both ends of each repeated k-mer until there is no more similarity between them, indicating the ends of the repeats.[47] Another group of algorithms employs a method called sequence self-comparison. Sequence self-comparison programs use databases such as AB-BLAST to conduct an initial sequence alignment. As these programs find groups of elements that partially overlap, they are useful for finding highly diverged transposons, or transposons with only a small region copied into other parts of the genome.[49] Another group of algorithms follows the periodicity approach. These algorithms perform a Fourier transformation on the sequence data, identifying periodicities, regions that are repeated periodically, and are able to use peaks in the resultant spectrum to find candidate repetitive elements. This method works best for tandem repeats, but can be used for dispersed repeats as well. However, it is a slow process, making it an unlikely choice for genome-scale analysis.[47]

The second step of de novo repeat identification involves building a consensus of each family of sequences. A consensus sequence is a sequence that is created based on the repeats that comprise a TE family. A base pair in a consensus is the one that occurred most often in the sequences being compared to make the consensus. For example, in a family of 50 repeats where 42 have a T base pair in the same position, the consensus sequence would have a T at this position as well, as the base pair is representative of the family as a whole at that particular position, and is most likely the base pair found in the family's ancestor at that position.[47] Once a consensus sequence has been made for each family, it is then possible to move on to further analysis, such as TE classification and genome masking in order to quantify the overall TE content of the genome.

Adaptive TEs

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Transposable elements have been recognized as good candidates for stimulating gene adaptation, through their ability to regulate the expression levels of nearby genes.[50] Combined with their "mobility", transposable elements can be relocated adjacent to their targeted genes, and control the expression levels of the gene, dependent upon the circumstances.

The study conducted in 2008, "High Rate of Recent Transposable Element–Induced Adaptation in Drosophila melanogaster", used D. melanogaster that had recently migrated from Africa to other parts of the world, as a basis for studying adaptations caused by transposable elements. Although most of the TEs were located on introns, the experiment showed a significant difference in gene expressions between the population in Africa and other parts of the world. The four TEs that caused the selective sweep were more prevalent in D. melanogaster from temperate climates, leading the researchers to conclude that the selective pressures of the climate prompted genetic adaptation.[51] From this experiment, it has been confirmed that adaptive TEs are prevalent in nature, by enabling organisms to adapt gene expression as a result of new selective pressures.

However, not all effects of adaptive TEs are beneficial to the population. In the research conducted in 2009, "A Recent Adaptive Transposable Element Insertion Near Highly Conserved Developmental Loci in Drosophila melanogaster", a TE, inserted between Jheh 2 and Jheh 3, revealed a downgrade in the expression level of both of the genes. Downregulation of such genes has caused Drosophila to exhibit extended developmental time and reduced egg to adult viability. Although this adaptation was observed in high frequency in all non-African populations, it was not fixed in any of them.[52] This is not hard to believe, since it is logical for a population to favor higher egg to adult viability, therefore trying to purge the trait caused by this specific TE adaptation.

At the same time, there have been several reports showing the advantageous adaptation caused by TEs. In the research done with silkworms, "An Adaptive Transposable Element insertion in the Regulatory Region of the EO Gene in the Domesticated Silkworm", a TE insertion was observed in the cis-regulatory region of the EO gene, which regulates molting hormone 20E, and enhanced expression was recorded. While populations without the TE insert are often unable to effectively regulate hormone 20E under starvation conditions, those with the insert had a more stable development, which resulted in higher developmental uniformity.[53]

These three experiments all demonstrated different ways in which TE insertions can be advantageous or disadvantageous, through means of regulating the expression level of adjacent genes. The field of adaptive TE research is still under development and more findings can be expected in the future.

TEs participates in gene control networks

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Recent studies have confirmed that TEs can contribute to the generation of transcription factors. However, how this process of contribution can have an impact on the participation of genome control networks. TEs are more common in many regions of the DNA and it makes up 45% of total human DNA. Also, TEs contributed to 16% of transcription factor binding sites. A larger number of motifs are also found in non-TE-derived DNA, and the number is larger than TE-derived DNA. All these factors correlate to the direct participation of TEs in many ways of gene control networks.[46]

See also

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Notes

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[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Transposable element

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from Grokipedia
Transposable elements (TEs), also known as transposons or jumping genes, are mobile segments of DNA that can relocate within a genome, either by a "cut-and-paste" mechanism or through an RNA intermediate in a "copy-and-paste" process, thereby influencing genetic structure and function. These elements, ranging from a few hundred to several thousand base pairs in length, are ubiquitous across prokaryotic and eukaryotic organisms and can encode proteins necessary for their own mobility, such as transposases or reverse transcriptases. Discovered by Barbara McClintock in the 1940s through her studies on maize chromosomes, TEs were initially observed as "controlling elements" that caused variable phenotypes in corn kernel coloration, challenging the prevailing view of the genome as static. Her groundbreaking work, for which she received the Nobel Prize in 1983, revealed that TEs could insert into or excise from genes, modulating their expression. TEs are broadly classified into two main categories based on their transposition mechanism. Class I TEs, or retrotransposons, transpose via an intermediate that is reverse-transcribed into DNA before reintegration; these include (LTR) retrotransposons, long interspersed nuclear elements (LINEs) like LINE-1, and short interspersed nuclear elements (SINEs) such as Alu sequences in . Class II TEs, or DNA transposons, move directly as DNA using a enzyme to excise and insert the element, with superfamilies including Tc1/mariner and hAT. Many TEs are non-autonomous, lacking the genes for mobility and instead relying on proteins from autonomous elements, which amplifies their proliferation. In most eukaryotic genomes, TEs constitute a substantial fraction, often exceeding 40% of the total DNA; for instance, they comprise approximately 45% of the and up to 85% in some like or . This abundance underscores their evolutionary significance, as TEs drive genome expansion, rearrangements, and innovation by shuffling exons, creating new regulatory sequences, or facilitating . However, unchecked TE activity can lead to deleterious effects, including that contributes to over 100 human genetic diseases and promotes genomic instability in cancers. Hosts counter this through epigenetic silencing mechanisms, such as and modifications, establishing a dynamic "" that shapes architecture over evolutionary time.

History

Discovery by Barbara McClintock

Barbara McClintock's pioneering work in maize cytogenetics during the 1940s revealed unexpected instabilities in genetic inheritance, challenging the prevailing view of the genome as a static entity. While studying chromosome structure and behavior in at the and later at , McClintock observed variegated patterns in kernel coloration, characterized by sectors of intense purple pigmentation amid colorless areas. These patterns arose from unstable mutations at the C (colored) and Wx (waxy) loci on , where gene expression would spontaneously revert or suppress, leading to mosaic phenotypes in plant tissues. McClintock's key experiments identified two interacting genetic components responsible for these phenomena: the Dissociation (Ds) element, which induced chromosome breakage and localized gene inactivation, and the Activator (Ac) element, which regulated Ds activity from a distance. In crosses involving plants with short arm deletions on , Ds was found to cause breaks at its insertion site near the , resulting in acentric fragments and dicentric bridges observable under ; Ac, located elsewhere on the chromosome, was required to trigger this transposition, as breakage occurred only in its presence. When Ds inserted into or near like C, it silenced their expression, producing pale sectors, but excision mediated by Ac could restore function, yielding colored spots whose size varied with the developmental timing of transposition—early excisions producing large sectors and late ones small spots. These observations demonstrated that Ds and Ac were mobile units capable of altering activity through insertion and excision. In the 1950s, McClintock formalized her findings in a series of publications, proposing the concept of "controlling elements" as autonomous genetic units that could transpose within the genome to regulate nearby genes. Her seminal paper in the 1950 Carnegie Institution of Washington Yearbook described the initial evidence for mutable loci and chromosome breakage, while her 1951 address at the Cold Spring Harbor Symposium on Quantitative Biology outlined the organizational role of these elements in genic expression. The most comprehensive account appeared in 1956 at another Cold Spring Harbor Symposium, where she detailed how Ac and Ds exemplified a regulatory system of mobile controllers that could inhibit, activate, or mutate genes based on their position and state. These works, though published in specialized venues like symposium proceedings and institutional reports, laid the groundwork for understanding transposons as dynamic components of eukaryotic genomes. Despite the rigor of her cytological and genetic evidence, McClintock faced significant skepticism from the in the decades following her announcements, as her ideas of gene mobility contradicted the era's central dogma emphasizing fixed linear inheritance. Her controlling elements were largely overlooked until the 1970s, when molecular studies confirmed transposable elements in —such as the IS elements discovered by Peter Starlinger and others—and extended to eukaryotes, validating McClintock's observations through and hybridization techniques. This molecular corroboration, including the identification of Ac and Ds as DNA transposons, culminated in widespread recognition of her contributions, leading to the awarding of the in Physiology or Medicine in 1983 as the sole recipient for the discovery of .

Key Developments Post-Discovery

Following Barbara McClintock's cytogenetic observations in maize during the 1940s and 1950s, molecular evidence for transposable elements emerged in the early 1970s with the discovery of bacterial insertion sequences (IS elements), short DNA segments capable of mobilizing within bacterial genomes and disrupting gene function, thereby confirming transposon activity at the DNA sequence level. These IS elements, first identified in Escherichia coli strains, such as IS1 by Saedler and Starlinger in 1972, ranged from 700 to 1,500 base pairs and featured inverted repeats at their ends, providing the first biochemical proof of genetic mobility in prokaryotes. Bridging to eukaryotic systems, in the early 1970s, and colleagues at the Institute of Molecular Biology in Moscow identified mobile dispersed genetic (mdg) elements in Drosophila melanogaster, providing the first molecular evidence of transposable elements in animal eukaryotic cells. Key findings included the characterization of mdg1 and mdg3 as repetitive DNA sequences capable of transposition via DNA intermediates, with mdg1 featuring long terminal repeat-like structures; these elements were among the earliest cloned eukaryotic transposons, influencing gene expression and marking a pivotal step in demonstrating biochemical proof of TE mobility in multicellular eukaryotes. In the 1980s, advances in enabled the identification of eukaryotic retrotransposons, which transpose via an intermediate. The Ty1 element in budding yeast (), discovered by Roeder and Fink in 1980, was the first long terminal repeat (LTR) retrotransposon shown to mobilize through reverse transcription, comprising up to 30 copies per genome and influencing . Concurrently, long interspersed nuclear elements (LINEs), particularly LINE-1 (L1), were characterized in the through sequencing efforts led by researchers like Singer in 1982, revealing these non-LTR retrotransposons as abundant repetitive sequences that amplify via target-primed reverse transcription. The development of restriction enzymes and molecular cloning techniques in the late 1970s and 1980s facilitated the isolation and manipulation of transposable elements from complex genomes. These tools allowed precise excision and ligation of DNA fragments, enabling the cloning of intact transposons for functional analysis; for instance, in Drosophila melanogaster, William Engels and colleagues in the 1980s used such methods to study P elements, DNA transposons responsible for hybrid dysgenesis, demonstrating their cut-and-paste transposition mechanism and role in generating mutations at rates exceeding 0.5% per generation in certain strains. Engels' work, including a 1983 study on P element origins, highlighted how these 2.9-kb elements invaded D. melanogaster populations recently, underscoring their evolutionary dynamics. The integration of transposable element research with large-scale accelerated in the late 1990s and early 2000s, culminating in the Project's 2001 draft sequence, which revealed that transposable elements constitute approximately 45% of the , primarily as ancient fossils like LINEs (17%) and (11%). This finding, from the International Human Genome Sequencing Consortium, shifted perceptions of TEs from mere "" to key drivers of genomic architecture, with active elements contributing to variation and disease. Post-2010 technological advances, particularly CRISPR-Cas systems, have enabled targeted editing of transposable elements for functional studies. Seminal work by Klompe et al. in 2019 introduced CRISPR-associated s (CASTs), hybrid tools combining Cas12a guide RNAs with transposase proteins to direct programmable DNA insertions without double-strand breaks, achieving up to 40% efficiency in bacterial models and facilitating precise TE mobilization assays. These tools have since been adapted for eukaryotic systems, allowing researchers to dissect TE regulatory roles, such as silencing mechanisms, and explore their contributions to and pathology. Subsequent milestones include the Telomere-to-Telomere (T2T) Consortium's 2022 assembly of the first complete, gapless (T2T-CHM13), which filled longstanding gaps in repetitive regions like centromeres and telomeres, revealing additional transposable element sequences and estimating that over 50% of the genome derives from TEs and other repeats. This advance provided a more accurate view of TE distribution and their role in genome structure. In 2023, researchers demonstrated efficient, double-strand break-free targeted DNA integration in cells using Type I-F CAST systems, achieving programmable insertion of large payloads with up to 10% efficiency, paving the way for therapeutic applications. By 2025, further optimizations, such as phage-assisted evolution of CAST variants, have enhanced integration specificity and efficiency in mammalian cells, expanding TE-based tools for .

Definition and Characteristics

Core Definition

Transposable elements (TEs), also known as transposons or jumping genes, are segments of DNA capable of moving or copying themselves to new locations within a genome. This mobility was first conceptualized by Barbara McClintock through her observations of genetic instability in maize chromosomes during the 1940s and 1950s. A defining property of TEs is their ability to insert into new genomic sites, which can disrupt or modify nearby genes, thereby influencing gene expression, genome structure, and evolutionary processes. Unlike viral genetic elements that can exit the cell and infect others, TEs are integral components of the host genome and remain confined to the individual cell lineage without intercellular transmission. TEs broadly fall into two categories based on their transposition mechanism: those that relocate directly as DNA (DNA transposons) and those that move via an RNA intermediate that is reverse-transcribed back into DNA (retrotransposons). In eukaryotic genomes, TEs constitute a significant portion, ranging from about 3% in species like budding yeast to over 80% in certain plants, with approximately 45-50% in the human genome.

Structural Features

Transposable elements (TEs) possess a modular that facilitates their integration and mobility within host genomes. A defining feature is their insertion mechanism, which generates flanking target site duplications (TSDs)—short direct repeats of the host DNA sequence, typically 2–15 base pairs in length, created by the staggered cleavage at the insertion point. This structural hallmark allows TEs to be readily identified in genomic sequences and reflects the precise enzymatic activity involved in their . Many TEs, particularly those from Class II (DNA transposons), are bounded by terminal inverted repeats (TIRs), which consist of short, inverted DNA sequences (often 10–50 base pairs) at each end of the element. These TIRs serve as binding sites for transposase enzymes, enabling recognition and excision or integration during transposition. In autonomous TEs, internal regions often contain one or more open reading frames (ORFs) encoding key proteins such as transposase for DNA transposons or reverse transcriptase for retroelements, providing the machinery for self-directed mobility. Non-autonomous TEs lack functional ORFs but retain structural elements like TIRs or other repeats to hijack proteins from autonomous counterparts. Both autonomous and non-autonomous TEs frequently incorporate non-coding regions, including promoters, insulators, and regulatory motifs, which can modulate structure or in proximity to insertion sites. TE sizes exhibit wide variation, reflecting their diverse evolutionary histories and functional constraints, from as small as ~100 base pairs in miniature inverted-repeat transposable elements (MITEs) to more than 10 kilobases in certain retrotransposons. This range influences their genomic impact, with smaller elements proliferating rapidly and larger ones contributing substantially to expansion.

Classification

Class I: Retrotransposons

Class I transposable elements, known as retrotransposons, are mobile genetic sequences that propagate through genomes via an intermediate, employing to synthesize for reintegration. This process follows a "copy-and-paste" mechanism, allowing retrotransposons to increase their copy number without excising from the original site, thereby contributing significantly to genomic expansion and diversity. Unlike DNA transposons, retrotransposons resemble retroviruses in their reliance on RNA-mediated transposition, though they lack an extracellular phase. Retrotransposons are broadly classified into two main subgroups based on structural features: those with long terminal repeats (LTRs) and those without (non-LTR). LTR retrotransposons are flanked by identical LTR sequences at both ends, which function as bidirectional promoters to drive transcription. These elements typically encode two key genes: , which produces structural proteins forming virus-like particles for reverse transcription, and pol, which encodes enzymatic proteins including for cDNA synthesis, integrase for genomic insertion, and often a for polyprotein processing. LTR retrotransposons belong to superfamilies such as Ty1/copia (exemplified by the Copia family) and Ty3/gypsy (exemplified by the Gypsy family), which are prevalent in and genomes, where they can constitute a substantial fraction of repetitive DNA. In contrast, non-LTR retrotransposons lack these terminal repeats and are transcribed from internal promoters. They include autonomous long interspersed nuclear elements (LINEs), such as L1 elements in mammals, which encode their own and endonuclease, and non-autonomous short interspersed nuclear elements (), which depend on LINE machinery for transposition. Prominent examples of retrotransposons illustrate their genomic impact. In humans, Alu elements—non-autonomous derived from 7SL —number over one million copies and comprise approximately 10% of the genome, influencing gene regulation and disease susceptibility through . Gypsy and Copia LTR retrotransposons, meanwhile, are major drivers of genome size variation in and animals, with Gypsy elements often dominating in species like and various . These elements highlight the dual role of retrotransposons as both evolutionary innovators and potential sources of genomic instability.

Class II: DNA Transposons

Class II transposons, also known as DNA transposons, are mobile genetic elements that transpose directly as DNA segments without an RNA intermediate, relying on the enzyme transposase to catalyze their movement within the genome. These elements are characterized by their ability to excise from one chromosomal location and insert into another, often via a cut-and-paste mechanism, though some variants employ replicative strategies. DNA transposons are found across diverse organisms, from bacteria to eukaryotes, and contribute significantly to genomic diversity and evolution. DNA transposons are broadly classified into several subgroups based on their structure and transposition mode, with terminal (TIR) transposons being the most abundant and well-studied. TIR transposons feature short sequences at their termini that serve as binding sites for the enzyme, and they encode a single (ORF) for production. Prominent TIR superfamilies include the Tc1/mariner family, widespread in animals and nematodes, and the hAT family, prevalent in and animals; for instance, the P elements belong to a TIR subgroup active in . Another TIR example is the Ac/Ds system in , where Ac is autonomous and Ds is non-autonomous, discovered as a key player in plant genome dynamics. In prokaryotes, insertion sequence (IS) elements represent simple TIR DNA transposons that typically span 700–2500 base pairs and mobilize short DNA segments. Other notable subgroups include Helitrons and Polintons, which diverge from the classic TIR structure. Helitrons operate via a rolling-circle replication mechanism and lack terminal repeats, instead featuring a 5'-TC and 3'-CTRR motif along with a near the 3' end; they encode a with a helicase-like domain and are abundant in plants and animals, often capturing host genes. Polintons, also called Maverick elements in some contexts, are large self-synthesizing DNA transposons (up to 20 kb) that encode their own and integrase, enabling autonomous replication and integration; they are found in protists, fungi, and animal genomes. The enzyme is central to function, typically containing a catalytic DDE domain—a triad of (D), (D), and (E) residues—that coordinates divalent metal ions to perform the nucleophilic attacks required for transposition. This domain is conserved across most superfamilies, ensuring precise cleavage and joining of DNA strands, though Helitrons and Polintons exhibit variations such as or fusions. While most DNA transposons propagate through a non-replicative cut-and-paste mode, where the element is excised and reinserted elsewhere, replicative copy-and-paste variants exist in subgroups like Helitrons and certain bacterial IS elements, allowing the original copy to remain while generating new insertions.

Autonomous and Non-Autonomous Elements

Transposable elements (TEs) are classified as autonomous or non-autonomous based on their ability to independently encode the proteins required for transposition. Autonomous TEs contain functional genes that produce essential enzymes, such as for DNA transposons or and integrase for retrotransposons, enabling them to mobilize themselves within the . In contrast, non-autonomous TEs lack these coding sequences due to mutations or deletions, rendering them incapable of self-mobilization; instead, they depend on the enzymatic machinery provided by co-existing autonomous TEs of the same or compatible families. This distinction applies across both Class I retrotransposons and Class II DNA transposons, influencing their propagation and genomic impact. Autonomous TEs, such as full-length LINE-1 (L1) elements in retrotransposons, encode open reading frames (ORFs) for ORF1p (a ) and ORF2p (with and endonuclease activities), allowing independent retrotransposition. Similarly, many DNA transposons, like those in the Tc1/mariner superfamily, produce a enzyme that catalyzes excision and reintegration. These elements represent the "driver" copies that sustain TE activity in a . Non-autonomous TEs, exemplified by short interspersed nuclear elements () such as Alu in and miniature inverted-repeat transposable elements (MITEs) derived from DNA transposons, have excised or degraded their enzymatic genes but retain regulatory signals like promoters or terminal repeats that hijack autonomous partners. For instance, Alu elements utilize the LINE-1 for their insertion, while MITEs rely on transposases from related autonomous DNA TEs. Non-autonomous TEs often evolve from autonomous counterparts through internal deletions, truncations, or point mutations that disrupt coding regions while preserving mobilization signals, leading to a proliferation of defective but mobilizable copies. may also originate de novo from non-TE sequences, such as polymerase III-transcribed genes (e.g., 7SL for Alu), and become parasitic upon acquiring compatibility with LINE machinery. In many eukaryotic genomes, non-autonomous TEs vastly outnumber their autonomous relatives, dominating repetitive DNA content due to their lower metabolic burden on the host and efficient parasitism. In the human genome, for example, approximately 500,000 truncated L1 elements lack full-length ORFs and cannot transpose independently, compared to only about 4,000 full-length copies, while over 1 million Alu elements—all non-autonomous—comprise around 10% of the total DNA. This prevalence underscores how non-autonomous elements amplify TE expansion without the need for their own enzymatic synthesis. The reliance of non-autonomous TEs on autonomous ones facilitates their rapid dissemination, as they avoid the risks and costs associated with encoding transposition proteins, thereby contributing disproportionately to inflation and structural variation across species. This dynamic can enhance but also increases the potential for deleterious insertions.

Other Categories

Beyond the conventional dichotomy of Class I retrotransposons and Class II DNA transposons, several atypical transposable elements (TEs) have been identified that do not fit neatly into these categories due to their unique structures, replication mechanisms, or evolutionary origins. These elements, often termed Class III TEs in some classifications or simply "other" categories, include short non-autonomous variants, rolling-circle replicators, large self-synthesizing units, and recombinase-dependent types. Their discovery largely stemmed from genomic sequencing efforts post-2000, which revealed these elements through bioinformatics analyses of repetitive DNA in eukaryotic genomes, filling gaps in the system established earlier. Miniature Inverted-Repeat Transposable Elements (MITEs) represent a prolific group of short, non-autonomous DNA transposons lacking coding potential but retaining terminal inverted repeats (TIRs) and transposase-binding sites derived from autonomous precursors. Typically 100–500 base pairs in length, MITEs amplify rapidly in genomes by parasitizing the transposase enzymes of full-length elements, enabling cut-and-paste transposition without their own enzymatic machinery. They are particularly abundant in plant genomes, such as rice and maize, where they occupy gene-rich regions and can influence nearby gene expression through insertion or promoter activity. First systematically characterized in the early 2000s via genome-wide surveys, MITEs exemplify how truncated derivatives can dominate TE landscapes despite their simplicity. Helitrons constitute another distinct category of DNA transposons that employ a rolling-circle replication mechanism, diverging from the typical TIR-flanked, cut-and-paste mode of Class II elements. These TEs lack inverted repeats and instead feature a 5′ TA dinucleotide target site duplication, with autonomous forms encoding a bifunctional Rep/ protein and a HUH endonuclease for nicking and replication. Non-autonomous Helitrons, which predominate, rely on these proteins in trans and are known for capturing host gene fragments during transposition, potentially contributing to exon shuffling. Predominantly found in plants like and animals including , Helitrons were uncovered in through computational detection of their hairpin structures in sequenced genomes. Polintons, also known as , are large (15–20 kb) self-synthesizing DNA transposons that encode a suite of proteins, including a protein-primed type B (pPolB), retroviral-like integrase, and major protein, suggesting evolutionary ties to double-stranded DNA viruses. Flanked by long TIRs (400–700 bp), they transpose via a copy-paste mechanism involving direct , independent of host polymerases. While present at low copy numbers in most eukaryotes, they expand dramatically in certain protists, such as , comprising up to one-third of the genome. Identified in the mid-2000s through metagenomic and phylogenetic studies, Polintons are hypothesized as progenitors of nucleocytoplasmic large DNA viruses. Cryptons form a rare subclass of DNA transposons mobilized by a recombinase (YR) rather than the DDE transposase typical of other Class II elements. Characterized by a simple structure with a single (ORF) encoding the YR and short TIRs, they integrate via akin to mechanisms. Primarily detected in fungi, , and some animals, Cryptons exhibit low abundance and have been linked to intron-encoded variants that may facilitate splicing-related mobility. Their recognition emerged around 2011 from , highlighting the diversity of recombinase-driven mobility in eukaryotes.

Mechanisms of Transposition

Retrotransposition Process

Retrotransposition is the mechanism by which Class I transposable elements, or retrotransposons, propagate within the through an RNA intermediate, resulting in new copies of the element being inserted at distant sites. This "copy-and-paste" contrasts with the direct DNA manipulation of Class II elements and relies on host cellular machinery for transcription and , while the element-encoded proteins handle reverse transcription and integration. The is exemplified by long interspersed nuclear elements (LINEs), particularly LINE-1 (L1), which are autonomous and encode the necessary enzymes, whereas short interspersed nuclear elements (SINEs) like Alu are non-autonomous and hijack L1 proteins for mobilization. The retrotransposition process begins with transcription of the DNA into a full-length intermediate by , often driven by an internal promoter within the element. This is then exported to the , where it serves as a template for into proteins, including (RT) and integrase-like activities. In LINE-1 elements, produces two open reading frame (ORF) proteins: ORF1p, which binds and facilitates ribonucleoprotein (RNP) complex formation, and ORF2p, a multifunctional enzyme encoding both endonuclease and RT domains essential for subsequent steps. The RNP complex, comprising the RNA and proteins, is transported back to the nucleus. In the nucleus, reverse transcription occurs via target-primed reverse transcription (TPRT), where ORF2p's endonuclease domain creates a single-strand nick in the target DNA, exposing a 3' hydroxyl (OH) group that primes the RT activity. The 3' end of the anneals to the nicked site, and ORF2p's RT domain synthesizes a cDNA copy using the as a template, initiating from the poly-A tail. This process is coupled with second-strand synthesis and integration, where the cDNA is inserted into the at the nick site, effectively creating a new insertion. For LINE-1, ORF2p's cysteine-rich domain may aid in final strand transfer, completing the integration without requiring a separate integrase. Variations exist between long terminal repeat (LTR) and non-LTR retrotransposons. Non-LTR elements, such as LINE-1, primarily use TPRT for integration and lack LTRs, relying on the poly-A signal for RNA stability. In contrast, LTR retrotransposons, including endogenous retroviruses (ERVs), form virus-like particles in the cytoplasm; their RNA is reverse-transcribed into double-stranded DNA using element-encoded gag, pol (RT and integrase), and sometimes env proteins, with LTRs providing promoter and polyadenylation signals to facilitate transcription. Integration for LTR elements involves the integrase domain cleaving target DNA and joining the cDNA ends, similar to retroviral mechanisms. The retrotransposition process is inherently error-prone, often leading to incomplete reverse transcription and the generation of target site duplications (TSDs) of 5-20 base pairs flanking the new insertion due to imprecise repair of the nicked site by host machinery. This mutagenic aspect contributes to genomic diversity but also potential instability, as seen in LINE-1 insertions that can disrupt genes.

DNA Transposon Mechanism

DNA transposons, also known as Class II transposable elements, mobilize within genomes through a cut-and-paste mechanism mediated by the enzyme transposase, which directly manipulates DNA without RNA intermediates. This process begins with transposase binding to the terminal inverted repeats (TIRs) that flank the transposon, forming a stable complex that recognizes specific sequences at the element's ends. The TIRs serve as primary binding sites, enabling the transposase to assemble into a synaptic complex, often dimeric or tetrameric, that pairs the transposon's two ends. The core catalytic activity resides in the DDE domain of the , characterized by two residues and one (or ) that coordinate divalent metal ions, such as Mg²⁺ or Mn²⁺, to facilitate hydrolysis and strand transfer reactions. Excision occurs via double-strand breaks at the transposon boundaries: the first cleaves the non-transferred strand, followed by of the transferred strand, releasing the transposon as a linear intermediate with 3'-OH groups at its ends. This excised element then integrates into a target site, where the catalyzes staggered cuts in the target DNA, typically 2–9 base pairs apart, allowing the transposon's 3'-OH ends to attack and form new . For instance, mariner and Tc1-like transposons preferentially target TA dinucleotides, generating a 2-base pair target site duplication (TSD) upon insertion. Following excision, the donor site retains a double-strand break with short overhangs, which host cellular repair machinery, such as (NHEJ), typically resolves, often leaving a small derived from the original TSD or repair artifacts. This repair can result in precise restoration in some cases, like with piggyBac transposons that excise without residual scars, but more commonly introduces minor alterations at the donor locus. In certain bacterial systems, such as bacteriophage Mu, transposition can proceed in a replicative mode, where the process couples with to generate a cointegrate intermediate, thereby increasing the transposon copy number rather than simply relocating it.

Copy-Paste vs Cut-and-Paste Dynamics

Transposable elements (TEs) propagate through distinct mechanisms that influence their abundance and genomic effects. The copy-paste mechanism, characteristic of retrotransposons, involves transcription into RNA, reverse transcription into DNA, and insertion of the new copy at a distant site, leaving the original element intact.01193-9) This replicative process enables exponential increases in copy number over evolutionary time, as each transposition event generates an additional copy without excising the donor. A prominent example is the Alu family of short interspersed nuclear elements (SINEs) in primates, which expanded in discrete amplification waves over the past 65 million years, contributing over one million copies to the human genome.00517-X) In contrast, the cut-and-paste mechanism predominates in DNA transposons, where the element is excised from its donor site via transposase-mediated double-strand breaks and reintegrated elsewhere, typically maintaining overall copy number unless coupled with host DNA replication.01193-9) This non-replicative transposition often occurs in the germline, as seen with P elements in Drosophila melanogaster, where precise excision and insertion during development can propagate the element across generations without net copy gain in somatic cells.90116-T) However, imprecise excision may leave gaps or footprints at the donor site, potentially leading to mutations. Certain DNA transposons exhibit hybrid replication strategies, such as Helitrons, which use a rolling-circle mechanism to generate multiple copies from a circular intermediate without target site duplications typical of cut-and-paste events. This allows for amplification similar to copy-paste while retaining DNA-based mobility, and Helitrons have proliferated extensively in plant genomes, such as . The copy-paste dynamics of retrotransposons drive proliferation and expansion, often accounting for significant portions of eukaryotic genomes—up to 45% in humans—through unchecked copy accumulation that can impose a mutational load. Conversely, cut-and-paste mechanisms in DNA transposons more frequently induce local genomic rearrangements, including deletions, inversions, or duplications at excision and insertion sites, fostering structural variation without broad copy number escalation. Detection of these dynamics relies on genomic signatures; for instance, copy-paste retrotransposons with long terminal repeats (LTRs) often leave solo LTRs as remnants of unequal between the 5' and 3' LTRs of paired elements, reducing full-length copies while preserving promoter activity. These solo LTRs serve as evolutionary markers of past amplification events in lineages like and humans.

Genomic Distribution

Locations in Eukaryotic Genomes

Transposable elements (TEs) in eukaryotic genomes display distinct insertion preferences that reflect a balance between transposition efficiency and host survival, often favoring non-coding regions to reduce mutational load. Introns represent a primary insertion site for many TEs, as this location minimizes disruption to essential protein-coding sequences and thus avoids immediate lethality; for instance, in mammalian genomes, a majority of de novo insertions, such as those from LINE-1 elements, occur within introns. TEs also accumulate in gene-poor regions, where they face less purifying selection, and in heterochromatic compartments like centromeres and telomeres, which provide sheltered environments for proliferation due to low recombination and gene density. In heterochromatin, TEs can constitute a substantial fraction of the sequence, such as up to 86% in the centromeres of certain protists like Dictyostelium discoideum. This heterochromatic enrichment arises from both preferential integration and retention, as TEs contribute to the formation of repressive chromatin marks like HP1 binding. Organism-specific patterns highlight the diversity of TE distributions. In plant genomes, TEs often dominate, comprising over 85% of the maize (Zea mays) genome, with (LTR) retrotransposons particularly enriched in pericentromeric and gene-poor regions, while non-LTR elements like Helitrons insert closer to genes. In (Saccharomyces cerevisiae), TEs such as Ty1 retrotransposons preferentially integrate upstream of genes transcribed by , such as tRNA and 5S rRNA genes, which may influence rDNA stability and . These patterns underscore how TE localization adapts to genomic architecture, with exhibiting higher overall TE loads in interstitial and heterochromatic zones compared to more compact genomes. Insertion biases further shape TE landscapes, with LINEs exhibiting a strong preference for AT-rich sequences due to the endonuclease target site (5'-TT/AAAA-3'), leading to their abundance in low-GC, gene-poor areas. In contrast, SINEs show a propensity for gene-proximal sites, often within or near transcribed regions; for example, in genomes, approximately 18% of are located within 1 kb upstream of genes, and up to 38% overlap transcribed regions in related like . Such biases result in TEs being enriched in evolutionarily younger genomic regions, where recent activity is evident—for instance, L1Hs-Ta subfamily insertions, representing the most recent waves, are predominantly found in introns of younger genes, reflecting ongoing retrotransposition dynamics. While these insertions generally tolerate host viability, they can occasionally generate functional novelties, such as new exons through exonization of TE sequences or novel regulatory elements that modulate nearby gene expression.

Presence in Prokaryotic Genomes

Transposable elements (TEs) in prokaryotic genomes primarily consist of DNA transposons, with insertion sequences (IS elements) representing the most abundant and simplest autonomous class. These short segments, typically 700–2500 base pairs long, encode a transposase enzyme that facilitates their mobility via a cut-and-paste mechanism. Composite transposons, such as those in the Tn family (e.g., Tn3, Tn5, Tn7), are larger structures formed by two IS elements flanking accessory genes, often conferring traits like antibiotic resistance. Unlike eukaryotic TEs, prokaryotic versions lack RNA intermediates and are generally smaller and more streamlined. IS elements and transposons comprise approximately 1–5% of many bacterial genomes, though this varies widely; for instance, some strains of harbor dozens of copies, while others like species may have hundreds. Transposases, the proteins encoded by these elements, are the most ubiquitous and abundant functional class across prokaryotic genomes, reflecting their pervasive presence in and . In archaeal genomes, IS elements are similarly diverse, with over 1,500 entries in databases like ISfinder, and species such as Sulfolobus solfataricus containing around 350 intact mobile elements. These TEs are often more numerous on plasmids than chromosomes, facilitating (HGT) and contributing to genomic plasticity. Prokaryotic TEs frequently insert near operons, pathogenicity islands, or replication forks, enhancing their role in adaptive evolution; for example, Tn5 in E. coli promotes the spread of resistance genes via mobilization. The Mu, a phage-like transposon, exemplifies replicative transposition, forming cointegrates that integrate viral DNA into bacterial chromosomes. Insertion biases favor intergenic regions, AT-rich sequences, or tRNA genes to reduce gene disruption, with archaeal IS elements showing similar preferences for non-coding areas. Compared to eukaryotes, where TEs can exceed 50% of genome content, prokaryotic elements maintain lower abundance but exhibit higher mobility due to shorter generation times and frequent HGT, enabling rapid dissemination across populations.

Biological Impacts

Deleterious Effects

Transposable elements (TEs) exert deleterious effects primarily through , where their integration into the disrupts essential genetic sequences. When a TE inserts into a of a , it can cause loss-of-function mutations by interrupting exons, altering splicing patterns, or introducing premature stop codons, thereby impairing protein production. In humans, retrotransposons such as LINE-1 (L1), Alu, and SVA elements have been implicated in over 200 cases of genetic disorders through direct insertions documented in the Human Gene Mutation Database. TE activity also promotes genomic instability via unequal recombination between homologous copies scattered throughout the genome. This non-allelic can lead to large-scale deletions, duplications, or inversions of chromosomal segments, exacerbating structural variations that contribute to susceptibility. For instance, recombination between Alu elements, which comprise over 10% of the , has been implicated in approximately 0.5% of human genomic disorders, including conditions like hemophilia and . Furthermore, TEs can induce epigenetic silencing of nearby genes as a host response to their presence, often through the spread of repressive modifications and . This heterochromatinization, intended to suppress TE mobility, inadvertently silences adjacent protein-coding genes, reducing their expression and potentially causing phenotypic abnormalities. In eukaryotes, such as in and , this trade-off between TE control and gene repression has been shown to preferentially eliminate TEs from gene-rich regions over evolutionary time, underscoring the fitness costs involved. A classic example of TE-induced deleterious effects is hybrid dysgenesis in Drosophila melanogaster, caused by uncontrolled transposition of P elements in the germline of hybrid offspring from crosses between P-strain males and M-strain females. This leads to sterility, mutations, and chromosomal aberrations due to rampant insertional activity, demonstrating how TE mobilization can devastate reproductive fitness in a single generation. These mutagenic insertions in Drosophila parallel extreme cases in humans, such as L1-mediated disruptions contributing to hemophilia A and colon cancer.

Roles in Gene Regulation

Transposable elements (TEs) play crucial roles in regulation by providing sequences that function as promoters, enhancers, and insulators, thereby influencing transcriptional control in mammalian genomes. These elements, once considered mere genomic parasites, have been co-opted to shape regulatory networks, particularly in where TE insertions near enable tissue-specific expression patterns. For instance, long terminal repeats (LTRs) from endogenous retroviruses (ERVs) act as enhancers that drive the expression of developmental in evolutionarily conserved manners across species. TE-derived promoters and enhancers are abundant in human regulatory landscapes. Alu elements, short interspersed nuclear elements () comprising about 10% of the , frequently serve as alternative promoters for nearby genes, such as in the case of the NF1 tumor suppressor where an upstream Alu sequence initiates tissue-specific transcription. Similarly, LTRs from ERV-9 elements function as promoters and enhancers for genes involved in embryonic and hematopoietic development, with these regulatory activities conserved among . Approximately 25% of human candidate cis-regulatory elements, including enhancers, are derived from TEs, highlighting their widespread contribution to transcriptional innovation. Insulators derived from TEs further refine gene regulation by establishing boundaries that prevent inappropriate enhancer-promoter interactions. Mammalian insertional retrotransposon () elements, tRNA-derived , exhibit insulator activity by blocking enhancer-mediated activation and acting as barriers to spreading, particularly in immune-related genes like those in the pathway. These MIR insulators are enriched at boundaries between active and repressive domains, ensuring precise spatial organization of regulatory elements. Beyond direct transcriptional control, TEs contribute to epigenetic modulation through their integration into piRNA clusters. PiRNA clusters, which are genomic loci producing PIWI-interacting RNAs to silence TEs, often incorporate sequences from diverse transposable elements, enabling targeted epigenetic repression of mobile elements and nearby genes via and modifications. This mechanism maintains genome stability while allowing TEs to indirectly regulate host in germ cells. TEs also promote by inserting into introns and creating novel splice sites, thereby expanding transcript diversity. Intronic Alu and LINE elements can exonize or alter splicing patterns, generating protein isoforms with adaptive functions, as seen in evolution where such events enhance regulatory flexibility without disrupting canonical transcripts.

Disease Associations

Transposable elements (TEs) contribute to human diseases primarily through , where their mobilization disrupts gene function, alters splicing, or activates oncogenic pathways. In cancer, somatic TE insertions can initiate tumorigenesis by inactivating tumor suppressors or driving expression. For instance, LINE-1 (L1) retrotransposition has been implicated in , where hypomethylation allows a "hot" L1 element to evade repression and insert into the gene, leading to its biallelic inactivation and tumor initiation in normal colon cells. Similarly, L1-mediated chimeric transcripts involving the MET have been observed in colorectal tumors, promoting through aberrant activation. In neurological disorders, TE insertions can cause loss-of-function mutations in genes critical for neuronal integrity. A prominent example is the SVA retrotransposon insertion in the TAF1 gene, which underlies X-linked dystonia-parkinsonism (XDP), a progressive neurodegenerative condition characterized by and ; the insertion disrupts TAF1 expression in the , leading to selective neuronal loss. This mechanism highlights how hominid-specific SVAs can contribute to brain-specific pathologies. TEs are also linked to bleeding disorders like hemophilia A, where de novo L1 insertions into the F8 cause severe disease. In reported cases, L1 sequences inserted into 14 of F8 lead to retention and frameshift mutations, abolishing production and resulting in a novel class of mutations observed in 2 out of 240 unrelated patients (approximately 0.8%) in an early study. Overall, TEs account for 0.1-1% of de novo mutations in s, with empirical rates of approximately one Alu, one L1, or one SVA insertion per 20-60 births, underscoring their modest but significant role in heritable disease risk. These insertional events often stem from deleterious effects like gene disruption, which can propagate through the . In therapeutic contexts, the use of TE-based , such as transposons, carries risks of that could activate proto-oncogenes or inactivate tumor suppressors, potentially leading to secondary malignancies, as evidenced by modeling in genomes.

Examples in Non-Human Organisms

In plants, the Ac/Ds transposable element system, discovered by , exemplifies how DNA transposons can induce visible phenotypic . The Dissociation (Ds) element inserts into genes controlling pigment production in kernels, such as the C or I loci, leading to unstable expression and characteristic spotting patterns on the layer when the Activator (Ac) element is present to mobilize Ds. This transposition causes chromosome breakage and gene inactivation, resulting in sectors of colorless tissue amid pigmented areas, a phenomenon McClintock termed "" due to the mutable nature of the loci. In , long terminal repeat (LTR) retrotransposons contribute to hybrid necrosis, a form of postzygotic isolation where incompatible alleles from parental lines trigger cell death and tissue necrosis in hybrid progeny. One such case involves an LTR retrotransposon insertion near regulatory regions, activating defense responses that lead to widespread and reduced viability in intraspecific japonica hybrids. In animals, P elements in cause hybrid dysgenesis, a sterility syndrome arising from dysregulated transposition in offspring of crosses between P strain males (carrying P elements) and M strain females (lacking them). This leads to gonadal atrophy, mutations, and male recombination, with transposition rates increasing dramatically in the due to the absence of maternal repressors, resulting in up to 1% of gametes carrying new insertions. In prokaryotes, the bacteriophage Mu transposon in induces mutations by random insertion into bacterial genes, disrupting essential functions and generating auxotrophic or morphological variants; its discovery as a transposable element revealed how Mu integration during lysogeny creates a high frequency of host mutations, up to 0.1% per generation. In fungi, the Ty1 retrotransposon in the budding yeast disrupts gene function through insertion, often into promoter regions or open reading frames, leading to loss-of-function phenotypes such as auxotrophy or altered mating. Ty1 mobilization creates solo LTRs upon excision or full-length copies upon retrotransposition, with insertions near tRNA genes promoting hot spots that affect up to 5% of the and causing observable growth defects in laboratory strains. Transposable elements also enhance pathogen in non-human organisms, as seen in the malaria parasite , where miniature inverted-repeat transposable elements (MITEs) and other mobile elements contribute to genomic plasticity near virulence loci like var genes, facilitating antigenic variation that evades host immunity and promotes severe disease outcomes in infected hosts. Experimental models leverage transposons for mutagenesis screens, such as the Sleeping Beauty system in (Danio rerio), where engineered transposons insert into protein-coding genes to create mutants, identifying developmental and disease-related phenotypes like fin malformations or tumor suppressors in forward genetic screens with over 10,000 independent insertions. This approach has mapped hundreds of genes essential for embryogenesis, providing insights into vertebrate biology analogous to human processes.

Transposition Regulation

Transposition Rates

Transposition rates of transposable elements (TEs) vary widely across organisms and contexts, typically ranging from 10^{-2} to 10^{-5} per per generation, reflecting the balance between proliferative potential and host constraints. In humans, for instance, the LINE-1 (L1) exhibits a insertion rate of approximately 1 in 100 births, contributing to de novo mutations observable in pedigrees. These rates are influenced by TE class: copy-paste mechanisms, such as those in , enable exponential copy number growth under favorable conditions, potentially amplifying TE abundance across generations if excision or deletion rates are low. Rates differ markedly between cell types and over an organism's lifespan. Transposition is generally higher in germline cells than in somatic tissues, as germline events can be heritable and drive evolutionary change, whereas somatic insertions are confined to individual lineages. Additionally, transposition activity often increases with age, particularly in somatic contexts, due to progressive relaxation of epigenetic silencing, as observed in Drosophila where TE mobilization rises in aging brains. Transposition rates are measured through methods that capture de novo insertions directly. Reporter assays, which track TE mobility via selectable markers in cell culture or model organisms, provide estimates of potential activity, often in the range of 10^{-4} to 10^{-5} per copy per generation in . Pedigree-based sequencing of families or populations detects insertions by comparing parent-offspring genomes, revealing rates like 10^{-5} per copy per generation in . Species-specific variations highlight ecological and genomic differences. In plants, rates can be elevated, with estimates around 10^{-3} per locus in certain Arabidopsis TE families under specific conditions, facilitating rapid adaptation. In contrast, mammals exhibit lower rates, such as 10^{-4} per copy per generation for active TEs in humans, constrained by robust mechanisms. This interspecies disparity underscores how transposition dynamics contribute variably to .

Induction Factors

Transposable elements (TEs) can be induced to transpose at higher rates by various cellular, environmental, and genetic cues that disrupt normal repression mechanisms, thereby enhancing their mobility within the . These induction factors often exploit host stress responses or developmental windows of vulnerability, leading to increased transposition events that may contribute to or instability. Understanding these triggers is crucial for elucidating how TEs interact with host physiology under specific conditions. Stressful conditions, such as DNA damage or environmental perturbations, frequently activate TE transcription and transposition. In the yeast Saccharomyces cerevisiae, the Ty1 retrotransposon is notably induced by DNA-damaging agents like methyl methanesulfonate (MMS) or ionizing radiation, which elevate Ty1 RNA levels and subsequent retrotransposition rates by up to 100-fold through activation of DNA damage response pathways. This induction is mediated in part by the environmental stress response (ESR), a conserved program that upregulates Ty1 expression in response to multiple stressors, including heat shock, where shifting cells from 25°C to 37°C triggers Ty1 LTR-driven transcription as part of broader genomic reprogramming. Similarly, nutrient stresses like adenine starvation or ethanol exposure can synergistically boost Ty1 mobility by altering chromatin accessibility and RNA polymerase recruitment to TE promoters. During development, TEs often exhibit germline-specific activation due to dynamic that temporarily erases repressive epigenetic marks. In mammalian , global demethylation and modification changes during primordial germ cell specification lead to derepression of endogenous retroviruses (ERVs) and LINE elements, enabling their transcription and potential transposition in this totipotent stage. This process involves factors like TET enzymes for and remodelers such as PRC1/2 complexes, which must be re-established post-reprogramming to silence TEs anew; failure in this re-silencing can result in elevated TE activity and meiotic defects. Genetic alterations, particularly mutations in host repressors, can dramatically enhance TE transposition by relieving inhibitory controls. In Drosophila melanogaster, the P cytotype—a maternally inherited repression state—relies on a 66 kDa repressor protein encoded by P elements themselves; mutations or absence of this repressor, as seen in certain strains, lead to uncontrolled P element mobilization, increasing transposition rates by orders of magnitude and causing gonadal sterility. Analogous repressor mutations in other systems, such as loss-of-function in piRNA pathway genes, similarly derepress TEs like LINE-1 in mammals, amplifying their insertional activity. Viral infections provide another potent induction cue, where exogenous retroviruses can mobilize endogenous retroviral elements (ERVs) through trans-complementation. In mice infected with an exogenous ecotropic (MuLV), polytropic ERVs are activated and recombine with the virus, leading to production of infectious recombinant viruses and increased ERV propagation via the viral reverse transcription machinery. This mobilization can disseminate ERV sequences across the , potentially altering host or immune responses. A classic example of induction through interstrain mating is hybrid dysgenesis in Drosophila, where crossing P-element-containing males with females lacking P elements (M cytotype) fails to transmit the repressor, resulting in dysgenic progeny with massively elevated P element transposition rates—up to 100 times baseline—manifesting as sterility, mutations, and chromosomal aberrations. This phenomenon highlights how reproductive barriers or strain-specific genetic backgrounds can trigger TE bursts, analogous to cross-species matings that disrupt co-evolved repression systems.

Host Defense Mechanisms

Cells employ multiple host defense mechanisms to suppress the activity and mobility of transposable elements (TEs), thereby maintaining genomic stability. Epigenetic is a primary , involving and specific histone modifications that sequester TEs into domains. Cytosine methylation of TE DNA prevents transcription by recruiting repressive protein complexes, while trimethylation of histone H3 at lysine 9 () marks and recruits (HP1), which further compacts to inhibit TE expression. This mechanism is conserved across eukaryotes and is particularly effective against repetitive TE sequences, as demonstrated in studies of fission yeast and mammals where disruption of H3K9 methyltransferases leads to TE derepression and genomic instability. RNA interference pathways provide another layer of defense, especially in the where TE activity poses a risk to integrity. PIWI-interacting RNAs (s) are 24-32 small RNAs that guide PIWI proteins to cleave TE transcripts or direct their epigenetic silencing. In , piRNAs target TEs such as I要素 and gypsy through a ping-pong amplification loop, where primary piRNAs initiate cleavage of sense TE transcripts, producing antisense piRNAs that amplify the response. This pathway is similarly active in mammals, where piRNAs silence and IAP elements in spermatogonia, preventing retrotransposition and ensuring heritable protection. Defects in piRNA biogenesis, as seen in models lacking MIWI2, result in increased TE insertions and sterility. DNA repair mechanisms mitigate the damage from TE excision events, which generate double-strand breaks (DSBs) at donor sites. (NHEJ) is the predominant pathway for repairing these DSBs, ligating broken ends with minimal homology and often introducing small insertions or deletions as footprints. In systems like transposons in vertebrates and P elements in , NHEJ factors such as Ku70/80 and efficiently seal excision sites, preventing chromosomal fragmentation. While NHEJ can tolerate imprecise repair, it effectively restores genome continuity, contrasting with homologous recombination which is less frequent in non-dividing cells. Protein-based repressors, such as KRAB-associated proteins (KRAB-ZFPs), provide sequence-specific silencing in vertebrates, particularly . These transcription factors bind directly to TE-derived sequences in the genome, recruiting the KAP1 (TRIM28) corepressor complex to induce and . In humans and other , expanded KRAB-ZFP families target evolutionarily young TEs like HERV-K, preventing their integration into regulatory regions. For instance, ZFP809 binds to primate-specific L1 elements, enforcing epigenetic repression during early embryogenesis. The evolution of these defenses reflects an ongoing with TEs, where host innovations counter TE evasion strategies. piRNA amplification loops exemplify this dynamic, as clusters of piRNA precursors evolve rapidly to incorporate sequences from newly invasive TEs, enabling adaptive silencing. In and mammals, this feedback mechanism amplifies piRNA production against active TEs, driving co-evolution where TE mutations escape recognition, prompting host adaptations like new piRNA cluster insertions. Similarly, KRAB-ZFP diversification in primates mirrors waves of activity, underscoring how defenses shape architecture over evolutionary time.

Evolutionary Role

Contribution to Genome Evolution

Transposable elements (TEs) play a pivotal role in by generating structural variations and expanding , thereby fostering diversity and adaptability across organisms. Through transposition and recombination, TEs introduce that alter architecture, often leading to long-term evolutionary changes. In eukaryotes, their proliferation contributes to the bulk of , while in prokaryotes, they enable gene mobilization essential for survival under selective pressures. TEs drive structural variations such as inversions and duplications primarily through ectopic recombination between homologous sequences. Inversions arise when TEs in opposite orientations mediate non-allelic homologous recombination (NAHR), resolving DNA breaks with inverted outcomes; for example, in genomes, 15 such TE-mediated inversions have been identified, with 73% showing recombination signatures. Duplications occur via similar mechanisms involving TEs in direct orientations, often through microhomology-mediated pathways; Alu elements, for instance, contribute to 80.5% of TE-mediated rearrangements in humans, with median microhomologies of 15 bp at breakpoints. These processes generate genomic diversity, influencing chromosomal stability and evolutionary divergence. In eukaryotes, TE proliferation significantly expands , particularly in where it correlates strongly with overall DNA content (r² = 0.68). (LTR) retrotransposons amplify via a copy-and-paste mechanism, inserting new copies that accumulate without immediate removal. This expansion is amplified in polyploid , where genome duplication relaxes epigenetic silencing, triggering TE bursts; for example, in with 1C values averaging 39.6 pg, non-LTR retrotransposons like Del-2 (with 240,000 copies) substantially contribute to the large . Counterbalancing mechanisms, such as illegitimate recombination, limit unchecked growth, but net proliferation shapes eukaryotic over evolutionary timescales. Horizontal transfer of TEs, though infrequent, enables interspecies movement and introduces novel elements into genomes. The exemplifies this in , where it was horizontally transferred from D. willistoni to D. melanogaster populations within the last century, leading to rapid proliferation and phenotypic effects like hybrid dysgenesis. Such transfers, detected via low nucleotide divergence between copies across lineages, underscore TEs' capacity to bypass vertical inheritance and accelerate evolutionary innovation. Fossil records of TEs, manifested as eroded ancient copies, provide evidence of historical transposition activity and genome dynamics. These defunct elements accumulate mutations over time, truncating sequences and losing original hallmarks, yet they comprise a large fraction of repetitive DNA—such as 21% LINEs and 9% endogenous retroviruses in humans. In mammals, only 80–100 full-length LINE-1 copies remain active, while most ancient insertions erode into fragments, recording past bursts that expanded and influenced regulatory evolution. In prokaryotes, TEs facilitate the shuffling of antibiotic resistance genes, enhancing bacterial adaptability through . Insertion sequences (IS) and composite transposons, like Tn10 for resistance, mobilize determinants by flanking and excising gene cassettes. Insertion sequence common regions (ISCRs) further promote dissemination across antibiotic classes via rolling-circle replication, as seen in integron-associated transfers in pathogens like . This shuffling drives the of resistance under selective pressures.

Adaptive Functions of TEs

Transposable elements (TEs) can confer fitness advantages to host organisms by providing raw material for novel functions, particularly in immune responses. In vertebrates, the recombination-activating genes RAG1 and RAG2, essential for V(D)J recombination in adaptive immunity, originated from a domesticated transposase complex derived from an ancient RAG-like transposon. This ProtoRAG element, identified in the genome of the lancelet Branchiostoma belcheri, encodes functional RAG1- and RAG2-like proteins that form an active DNA transposase, enabling the excision and integration of DNA segments analogous to the mechanism repurposed for generating antibody and T-cell receptor diversity in jawed vertebrates. The co-option of this TE-derived machinery approximately 500 million years ago allowed vertebrates to evolve a sophisticated adaptive immune system capable of recognizing diverse pathogens, highlighting TEs as key drivers of immunological innovation. TEs also facilitate adaptation to environmental stresses by inducing mutations that enhance survival under adverse conditions. In the fission yeast Schizosaccharomyces pombe, stress-induced mobilization of the Tf2 generates insertions that upregulate stress response genes, such as those involved in biosynthesis, enabling rapid adaptation to nutrient limitation or temperature extremes. Similarly, in , TEs contribute to stress tolerance through and regulatory changes. In speciation processes, differences in TE regulation between diverging populations can lead to hybrid incompatibilities that reinforce reproductive isolation. In Drosophila species, such as D. simulans and D. mauritiana, mismatched epigenetic silencing of TEs like I elements in hybrids triggers ectopic transposition, causing gonadal sterility and reduced hybrid fitness, which promotes speciation by limiting gene flow.

Identification and Analysis

De Novo Detection Methods

De novo detection of transposable elements (TEs) relies on strategies that identify novel sequences without relying on existing annotations, encompassing both experimental and early computational approaches. Experimental methods, such as transposon tagging, involve introducing mobile elements into the genome to generate insertions that disrupt gene function, allowing for the isolation and characterization of new TEs. In Arabidopsis thaliana, the Ac/Ds transposon system has been widely used for mutagenesis, where the Dissociation (Ds) element inserts randomly, and reporter genes like β-glucuronidase (GUS) facilitate visual detection of insertion sites in mutant plants, enabling cloning and sequencing of the tagged regions to reveal TE structures. This approach has been instrumental in discovering TE families by linking phenotypic changes to genomic insertions, particularly in forward genetic screens. Early computational strategies for de novo TE detection focus on assembling contigs from high-copy repetitive sequences in unannotated , often using tools like precursors to RepeatMasker that perform self-comparisons to identify dispersed repeats. These methods involve fragmenting the , aligning sequences to detect similarities indicative of transposition, and reconstructing consensus models from multiple copies to define novel TE families. For instance, by clustering sequences based on similarity thresholds and extending matches to form longer contigs, researchers can delineate autonomous and non-autonomous elements without prior libraries. Key criteria for confirming de novo candidates as TEs include a minimum length typically exceeding several hundred base pairs, the generation of a reliable family from aligned copies, and evidence of target site preferences, such as short target site duplications (TSDs) of 2–15 base pairs flanking insertions, which arise from the repair mechanism during transposition. These features distinguish mobile elements from other repeats, with TSD length often family-specific (e.g., 3 bp for many DNA transposons). A major challenge in de novo detection is differentiating TEs from tandem repeats, as both can exhibit high copy numbers and sequence similarity, but TEs are typically dispersed while tandem arrays are contiguous and head-to-tail oriented; misclassification often occurs in regions of TE clustering or assembly gaps. Historically, these methods were pivotal in early genome projects, such as the 2002 draft sequencing of the rice () genome, where de novo repeat identification revealed that TEs comprised approximately 35% of the assembly, with a substantial portion representing novel families not previously annotated in other species. This effort highlighted the prevalence of lineage-specific TEs and set the stage for refined detection pipelines.

Computational Tools and Techniques

Computational tools for transposable element (TE) analysis primarily rely on two algorithmic paradigms: homology-based and methods. Homology-based approaches, such as those employing BLAST alignments against curated TE libraries, identify known TE families by detecting sequence similarities, often achieving high specificity for well-characterized elements but requiring pre-existing reference databases. In contrast, methods detect novel TEs without prior knowledge, utilizing techniques like hidden Markov models (HMMs) to model structural features such as terminal inverted repeats (TIRs) in DNA transposons, enabling the discovery of lineage-specific or diverged elements that homology searches might miss. These algorithms form the foundation for integrated pipelines that combine both strategies to enhance comprehensiveness. Prominent pipelines include REPET, which facilitates TE structural modeling through its TEdenovo module for de novo consensus building and TEannot for annotation, incorporating tools like PASTEC for classification based on structural and sequence features. Similarly, EDTA (Extensive de Novo TE Annotator) is tailored for eukaryotic genomes, integrating homology searches, structural prediction, and de novo repeat finding to produce accurate TE libraries while minimizing false positives. These tools output standardized formats like GFF3, supporting downstream analyses such as genome masking. Integration with long-read sequencing technologies, such as PacBio, has revolutionized the resolution of complex TE structures, particularly nested insertions where short reads fail due to repetitiveness. By spanning kilobase-scale regions, PacBio data enables precise assembly and annotation of nested TEs, as demonstrated in populations where it uncovered 58% more insertions than short-read methods, including novel families like TRIMs within existing elements. Post-2020 advances incorporate , with models improving TE boundary detection for finer-grained annotations. For instance, HiTE employs dynamic boundary adjustment to refine TE models, achieving higher accuracy in delineating insertion sites compared to traditional tools. Likewise, adapts convolutional neural networks from to identify and classify TEs directly from genomic sequences, enhancing de novo discovery in repetitive contexts. More recent developments as of 2025 include panHiTE, a for accurate TE detection in pangenomes, and TEtrimmer for automating manual curation. In applications like genome assembly polishing, these tools are pivotal in human projects, where TEs contribute to structural variants (SVs) such as Alu and L1 insertions, comprising a significant portion of non-reference sequences. Repeat-aware polishing strategies in the Human Reference Consortium leverage TE annotations to correct errors in repetitive regions, improving SV genotyping accuracy across diverse haplotypes.

References

  1. https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1577-z
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC8293684/
  3. https://www.nature.com/scitable/topicpage/transposons-the-jumping-genes-518
  4. https://www.nobelprize.org/prizes/medicine/1983/press-release/
  5. https://pmc.ncbi.nlm.nih.gov/articles/PMC3528533/
  6. https://www.pnas.org/doi/10.1073/pnas.1219372109
  7. https://karger.com/cgr/article/109/1-3/90/61616/McClintock-s-controlling-elements-the-full-story
  8. https://symposium.cshlp.org/content/21/197
  9. https://carnegiescience.edu/news/barbara-mcclintock-visionary-ahead-her-time
  10. https://journals.asm.org/doi/10.1128/microbiolspec.mdna3-0030-2014
  11. https://pmc.ncbi.nlm.nih.gov/articles/PMC4196381/
  12. https://pmc.ncbi.nlm.nih.gov/articles/PMC4399242/
  13. https://www.pnas.org/doi/10.1073/pnas.0404838101
  14. https://pmc.ncbi.nlm.nih.gov/articles/PMC10734217/
  15. https://www.science.org/doi/10.1126/science.abj6987
  16. https://www.nature.com/articles/s41587-023-01748-1
  17. https://www.science.org/doi/10.1126/science.adt5199
  18. https://doi.org/10.1016/j.cub.2022.07.044
  19. https://www.nature.com/scitable/topicpage/transposons-the-jumping-genes-518/
  20. https://bionumbers.hms.harvard.edu/bionumber.aspx?s=n&v=5&id=103831
  21. https://pmc.ncbi.nlm.nih.gov/articles/PMC1693792/
  22. https://doi.org/10.3390/genes12060918
  23. https://doi.org/10.1186/s13059-018-1577-z
  24. https://pmc.ncbi.nlm.nih.gov/articles/PMC10671454/
  25. https://pmc.ncbi.nlm.nih.gov/articles/PMC403668/
  26. https://pmc.ncbi.nlm.nih.gov/articles/PMC463057/
  27. https://pmc.ncbi.nlm.nih.gov/articles/PMC8220671/
  28. https://content.csbs.utah.edu/~rogers/tch/bio5410/Readings/Casacuberta-G-311-1.pdf
  29. https://wesslerlab.ucr.edu/sites/default/files/2020-10/the_implicit_genome.pdf
  30. https://pmc.ncbi.nlm.nih.gov/articles/PMC525682/
  31. https://wesslerlab.ucr.edu/sites/g/files/rcwecm5116/files/2020-10/ltr_mites.pdf
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC2874221/
  33. https://academic.oup.com/gbe/article/doi/10.1093/gbe/evq080/572849
  34. https://mobilednajournal.biomedcentral.com/articles/10.1186/s13100-021-00259-7
  35. https://pmc.ncbi.nlm.nih.gov/articles/PMC7325037/
  36. https://bdt.semi.ac.cn/download/0.0191464576650473.pdf
  37. https://www.pnas.org/doi/10.1073/pnas.0905563106
  38. https://www.pnas.org/doi/10.1073/pnas.0600833103
  39. https://pmc.ncbi.nlm.nih.gov/articles/PMC2991504/
  40. https://www.annualreviews.org/doi/10.1146/annurev-genet-040620-022145
  41. https://genomebiology.biomedcentral.com/articles/10.1186/gb-2009-10-9-r100
  42. https://pmc.ncbi.nlm.nih.gov/articles/PMC6177209/
  43. https://genomebiology.biomedcentral.com/articles/10.1186/gb-2011-12-12-236
  44. https://doi.org/10.1146/annurev-genet-040620-022145
  45. https://doi.org/10.1105/tpc.010235
  46. https://doi.org/10.1073/pnas.151269298
  47. https://doi.org/10.1016/j.gene.2006.08.008
  48. https://doi.org/10.3389/fgene.2023.1290146
  49. https://doi.org/10.1101/gr.201814.115
  50. https://doi.org/10.1101/gr.196238.115
  51. https://doi.org/10.1038/332164a0
  52. https://pmc.ncbi.nlm.nih.gov/articles/PMC7422641/
  53. https://www.pnas.org/doi/10.1073/pnas.1104208108
  54. https://pmc.ncbi.nlm.nih.gov/articles/PMC262663/
  55. https://jbiomedsci.biomedcentral.com/articles/10.1186/1423-0127-20-92
  56. https://www.science.org/doi/10.1126/science.338.6108.758
  57. https://www.science.org/doi/10.1126/science.1653452
  58. https://www.pnas.org/doi/10.1073/pnas.151269298
  59. https://www.pnas.org/doi/10.1073/pnas.0609601104
  60. https://www.nature.com/articles/s12276-021-00586-y
  61. https://www.pnas.org/doi/10.1073/pnas.0605618103
  62. https://www.nature.com/articles/s41467-024-47501-3
  63. https://pmc.ncbi.nlm.nih.gov/articles/PMC7190074/
  64. https://pmc.ncbi.nlm.nih.gov/articles/PMC98933/
  65. https://pmc.ncbi.nlm.nih.gov/articles/PMC1847376/
  66. https://pmc.ncbi.nlm.nih.gov/articles/PMC2910039/
  67. https://www.nature.com/articles/ismej2015192
  68. https://www.sciencedirect.com/science/article/pii/S2666979X24000314
  69. https://pubmed.ncbi.nlm.nih.gov/18724056/
  70. https://pmc.ncbi.nlm.nih.gov/articles/PMC2720190/
  71. https://pubmed.ncbi.nlm.nih.gov/26104714/
  72. https://biosci-batzerlab.biology.lsu.edu/Publications/Callinan_Retrotransposable.pdf
  73. https://www.nature.com/articles/s41580-022-00457-y
  74. https://pmc.ncbi.nlm.nih.gov/articles/PMC1636486/
  75. https://doi.org/10.1128/JVI.76.5.2410-2423.2002
  76. https://www.nature.com/articles/s41467-024-51921-6
  77. https://www.pnas.org/doi/10.1073/pnas.1507253112
  78. https://pmc.ncbi.nlm.nih.gov/articles/PMC3256352/
  79. https://www.sciencedirect.com/science/article/pii/S009286742401328X
  80. https://genome.cshlp.org/content/26/6/745.full
  81. https://www.sciencedirect.com/science/article/abs/pii/S2210776219303904
  82. https://pubmed.ncbi.nlm.nih.gov/2831458/
  83. https://pmc.ncbi.nlm.nih.gov/articles/PMC6771411/
  84. https://pmc.ncbi.nlm.nih.gov/articles/PMC3602164/
  85. https://www.pnas.org/doi/10.1073/pnas.36.6.344
  86. https://pmc.ncbi.nlm.nih.gov/articles/PMC6382335/
  87. https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-7-282
  88. https://pmc.ncbi.nlm.nih.gov/articles/PMC9138309/
  89. https://pmc.ncbi.nlm.nih.gov/articles/PMC6240941/
  90. https://pmc.ncbi.nlm.nih.gov/articles/PMC3612533/
  91. https://pmc.ncbi.nlm.nih.gov/articles/PMC6035798/
  92. https://pmc.ncbi.nlm.nih.gov/articles/PMC5056045/
  93. https://pmc.ncbi.nlm.nih.gov/articles/PMC2871824/
  94. https://pmc.ncbi.nlm.nih.gov/articles/PMC8594854/
  95. https://www.nature.com/articles/s41467-019-11385-5
  96. https://pmc.ncbi.nlm.nih.gov/articles/PMC8594186/
  97. https://pmc.ncbi.nlm.nih.gov/articles/PMC10309086/
  98. https://genomebiology.biomedcentral.com/articles/10.1186/s13059-021-02550-5
  99. https://pmc.ncbi.nlm.nih.gov/articles/PMC9559041/
  100. https://www.sciencedirect.com/science/article/pii/S0968000415002583
  101. https://pubmed.ncbi.nlm.nih.gov/15590325/
  102. https://pmc.ncbi.nlm.nih.gov/articles/PMC5659910/
  103. https://www.science.org/doi/10.1126/sciadv.aba3200
  104. https://pmc.ncbi.nlm.nih.gov/articles/PMC6988346/
  105. https://www.annualreviews.org/doi/10.1146/annurev-genet-112618-043717
  106. https://www.nature.com/articles/s41467-022-34810-8
  107. https://pmc.ncbi.nlm.nih.gov/articles/PMC4196380/
  108. https://www.nature.com/articles/s41467-020-15149-4
  109. https://wires.onlinelibrary.wiley.com/doi/full/10.1002/wrna.70022
  110. https://onlinelibrary.wiley.com/doi/10.1111/mec.12170
  111. https://www.cell.com/cell/fulltext/S0092-8674(16)30583-9
  112. https://www.pnas.org/doi/10.1073/pnas.0509720103
  113. https://pmc.ncbi.nlm.nih.gov/articles/PMC6314160/
  114. https://pubmed.ncbi.nlm.nih.gov/11540642/
  115. https://link.springer.com/article/10.1007/BF00290357
  116. https://www.repeatmasker.org/
  117. https://www.nature.com/articles/hdy2009165
  118. https://pmc.ncbi.nlm.nih.gov/articles/PMC8969392/
  119. https://mobilednajournal.biomedcentral.com/articles/10.1186/s13100-024-00323-y
  120. https://pmc.ncbi.nlm.nih.gov/articles/PMC3389668/
  121. https://pmc.ncbi.nlm.nih.gov/articles/PMC3107183/
  122. https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.0010022
  123. https://bio.tools/repet
  124. https://doi.org/10.1007/978-1-0716-1134-0_4
  125. https://www.nature.com/articles/s41467-022-29518-8
  126. https://www.nature.com/articles/s41467-024-49912-8
  127. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0291925
  128. https://www.biorxiv.org/content/10.1101/2025.02.15.638472v1
  129. https://www.nature.com/articles/s41467-025-63889-y
  130. https://www.nature.com/articles/s41586-023-05896-x
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