Tc1/mariner

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Tc1/mariner is a class and superfamily of interspersed repeats DNA (Class II) transposons. [1] The elements of this class are found in all animals, [2] including humans. They can also be found in protists and bacteria. [3] [4]

Contents

The class is named after its two best-studied members, the Tc1 transposon of Caenorhabditis elegans and the mariner transposon of Drosophila .

Structure

A. Structure of DNA transposons (Mariner type). B. Mechanism of transposition DNA Transposon.png
A. Structure of DNA transposons (Mariner type). B. Mechanism of transposition

The transposon consists of a transposase gene, flanked by two terminal inverted repeats (TIR). Two short tandem site duplications (TSD) are present on both sides of the insert. Transposition happens when two transposases recognize and bind to TIR sequences, join together 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. [5] In the IS630/Tc1/mariner system, the motif used is a "TA" dinucleotide, duplicated on both ends after insertion.

When the transposase gene is not carried by the transposon, it becomes a non-autonomous in that it now requires the gene to be expressed elsewhere to move around.

Transposase

Transposase, type 1 (partial DDE domain)
Identifiers
SymbolTranspotase_1
Pfam PF01359
Pfam clan CL0219
InterPro IPR001888
CATH 4u7b
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
HTH domain in Mos1 transposase
Identifiers
SymbolHTH_48
Pfam PF17906
Pfam clan CL0123
InterPro IPR041426
CATH 4u7b
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Structural features of SB transposase. SBTS2.png
Structural features of SB transposase.

The 360-amino acid polypeptide has three major subdomains: the amino-terminal DNA-recognition domain that is responsible for binding to the DR sequences in the mirrored IR/DR sequences of the transposon, a nuclear localization sequence (NLS), and a DDE domain that catalyzes the cut-and-paste set of reactions that comprise transposition. The DNA-recognition domain has two paired box sequences that can bind to DNA and are related to various motifs found on some transcription factors; the two paired boxes are labeled PAI and RED, both having the helix-turn-helix motif common for DNA-binding domains. The catalytic domain has the hallmark DDE (sometimes DDD) amino acids that are found in many transposase and recombinase enzymes. In addition, there is a region that is highly enriched in glycine (G) amino acids.

Several signatures for the superfamily of transcriptases have been given in various domain databases given the multi-domain nature of the protein. In addition, each domain are often represented by multiple entries, such as PF17906 / PF01710 / PF11427 among others for the "PAI" half of the box. The RED box is similarly diverse ( PF08279 / PF13412 / PF01498 , etc.) and is often in a winged HTH form for DNA recognition.

Sub-groups

The Tc1/mariner superfamily is generally subdivided by the catalytic domains of its transposase. It generally use a DDE (Asp-Asp-Glu) or DDD catalytic triad.

Tc1

Tc1 (DD34E) is a transposon active in Caenorhabditis elegans . [6] [7] There are also Tc1-like transposons in humans, all inactive. Tc1-like elements are present in other lower vertebrates, including several fish species and amphibians. [8]

In C. elegans, it is a 1610 base-pair long sequence. [9] Experiments show that this element "jumps" in human cells, with its transposase as the only protein required. [10]

Another example of this family is Tc3, also a transposon found in C. elegans. [11]

Mariner

Mariner (DD34D) elements are found in multiple species, including humans. [12] [13] The Mariner transposon was first discovered by Jacobson and Hartl in Drosophila in 1986. [14] A classification of the group was published in 1993, which divided such sequences in insects into the mauritiana, cecropia, mellifera, irritans, and capitata subfamilies, after the types of insects they are found in. [15] The classification does extend to other species.

This transposable element is known for its uncanny ability to be transmitted horizontally in many species. [16] [17] There are an estimated 14,000 copies of Mariner in the human genome comprising 2.6 million base pairs. [18] The first mariner-element transposons outside of animals were found in Trichomonas vaginalis . [19]

Human Mariner-like transposons are divided into Hsmar1 (cecropia) and Hsmar2 (irritans) 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. [20] Hsmar2 has been reconstructed multiple times from the fossil sequences. [21]

Mos1 (for Mosaic element) was discovered in Drosophila mauritiana . [22] The Himar1 element has been isolated from the horn fly, Haematobia irritans and can be used as a genetic tool in Escherichia coli . [23]

Other families

The rosa (DD41D) family is a family found in Ceratitis rosa . [24] Pogo/Fot1 (DDxD) is yet another family in this superfamily, x indicating a variable length. IS630, a mobile element in Shigella sonnei , also belongs to this superfamily. [4]

A few additional new families with different lengths between the triads have been reported. [25]

Pogo, also known as Tigger in humans, [26] has been domesticated by humans and yeast alike into the CENPB gene. Other human domestications of pogo include TIGD1, TIGD2, TIGD3, TIGD4, TIGD5, TIGD6, TIGD7, JRK, JRKL, POGK, and POGZ. [27]

See also

Related Research Articles

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A transposable element is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transposition often results in duplication of the same genetic material. In the human genome, L1 and Alu elements are two examples. Barbara McClintock's discovery of them earned her a Nobel Prize in 1983. Its importance in personalized medicine is becoming increasingly relevant, as well as gaining more attention in data analytics given the difficulty of analysis in very high dimensional spaces.

<span class="mw-page-title-main">Horizontal gene transfer</span> Type of nonhereditary genetic change

Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the evolution of many organisms. HGT is influencing scientific understanding of higher order evolution while more significantly shifting perspectives on bacterial evolution.

<span class="mw-page-title-main">Retrotransposon</span> Type of genetic component

Retrotransposons are a type of genetic component that copy and paste themselves into different genomic locations (transposon) by converting RNA back into DNA through the reverse transcription process using an RNA transposition intermediate.

A transposase is any of a class of enzymes capable of binding to the end of a transposon and catalysing its movement to another part of a genome, typically by a cut-and-paste mechanism or a replicative mechanism, in a process known as transposition. The word "transposase" was first coined by the individuals who cloned the enzyme required for transposition of the Tn3 transposon. The existence of transposons was postulated in the late 1940s by Barbara McClintock, who was studying the inheritance of maize, but the actual molecular basis for transposition was described by later groups. McClintock discovered that some segments of chromosomes changed their position, jumping between different loci or from one chromosome to another. The repositioning of these transposons allowed other genes for pigment to be expressed. Transposition in maize causes changes in color; however, in other organisms, such as bacteria, it can cause antibiotic resistance. Transposition is also important in creating genetic diversity within species and generating adaptability to changing living conditions.

P elements are transposable elements that were discovered in Drosophila as the causative agents of genetic traits called hybrid dysgenesis. The transposon is responsible for the P trait of the P element and it is found only in wild flies. They are also found in many other eukaryotes.

<span class="mw-page-title-main">Insertion sequence</span>

Insertion element is a short DNA sequence that acts as a simple transposable element. Insertion sequences have two major characteristics: they are small relative to other transposable elements and only code for proteins implicated in the transposition activity. These proteins are usually the transposase which catalyses the enzymatic reaction allowing the IS to move, and also one regulatory protein which either stimulates or inhibits the transposition activity. The coding region in an insertion sequence is usually flanked by inverted repeats. For example, the well-known IS911 is flanked by two 36bp inverted repeat extremities and the coding region has two genes partially overlapping orfA and orfAB, coding the transposase (OrfAB) and a regulatory protein (OrfA). A particular insertion sequence may be named according to the form ISn, where n is a number ; this is not the only naming scheme used, however. Although insertion sequences are usually discussed in the context of prokaryotic genomes, certain eukaryotic DNA sequences belonging to the family of Tc1/mariner transposable elements may be considered to be, insertion sequences.

Exon shuffling is a molecular mechanism for the formation of new genes. It is a process through which two or more exons from different genes can be brought together ectopically, or the same exon can be duplicated, to create a new exon-intron structure. There are different mechanisms through which exon shuffling occurs: transposon mediated exon shuffling, crossover during sexual recombination of parental genomes and illegitimate recombination.

<span class="mw-page-title-main">Mobile genetic elements</span> DNA sequence whose position in the genome is variable

Mobile genetic elements (MGEs) sometimes called selfish genetic elements are a type of genetic material that can move around within a genome, or that can be transferred from one species or replicon to another. MGEs are found in all organisms. In humans, approximately 50% of the genome is thought to be MGEs. MGEs play a distinct role in evolution. Gene duplication events can also happen through the mechanism of MGEs. MGEs can also cause mutations in protein coding regions, which alters the protein functions. These mechanisms can also rearrange genes in the host genome generating variation. These mechanism can increase fitness by gaining new or additional functions. An example of MGEs in evolutionary context are that virulence factors and antibiotic resistance genes of MGEs can be transported to share genetic code with neighboring bacteria. However, MGEs can also decrease fitness by introducing disease-causing alleles or mutations. The set of MGEs in an organism is called a mobilome, which is composed of a large number of plasmids, transposons and viruses.

<span class="mw-page-title-main">SETMAR</span> Protein-coding gene in the species Homo sapiens

Histone-lysine N-methyltransferase SETMAR is an enzyme that in humans is encoded by the SETMAR gene.

Transposon mutagenesis, or transposition mutagenesis, is a biological process that allows genes to be transferred to a host organism's chromosome, interrupting or modifying the function of an extant gene on the chromosome and causing mutation. Transposon mutagenesis is much more effective than chemical mutagenesis, with a higher mutation frequency and a lower chance of killing the organism. Other advantages include being able to induce single hit mutations, being able to incorporate selectable markers in strain construction, and being able to recover genes after mutagenesis. Disadvantages include the low frequency of transposition in living systems, and the inaccuracy of most transposition systems.

<span class="mw-page-title-main">Knockout rat</span> Type of genetically engineered rat

A knockout rat is a genetically engineered rat with a single gene turned off through a targeted mutation used for academic and pharmaceutical research. Knockout rats can mimic human diseases and are important tools for studying gene function and for drug discovery and development. The production of knockout rats was not economically or technically feasible until 2008.

Helitrons are one of the three groups of eukaryotic class 2 transposable elements (TEs) so far described. They are the eukaryotic rolling-circle transposable elements which are hypothesized to transpose by a rolling circle replication mechanism via a single-stranded DNA intermediate. They were first discovered in plants and in the nematode Caenorhabditis elegans, and now they have been identified in a diverse range of species, from protists to mammals. Helitrons make up a substantial fraction of many genomes where non-autonomous elements frequently outnumber the putative autonomous partner. Helitrons seem to have a major role in the evolution of host genomes. They frequently capture diverse host genes, some of which can evolve into novel host genes or become essential for Helitron transposition.

Transposons are semi-parasitic DNA sequences which can replicate and spread through the host's genome. They can be harnessed as a genetic tool for analysis of gene and protein function. The use of transposons is well-developed in Drosophila and in Thale cress and bacteria such as Escherichia coli.

The Sleeping Beauty transposon system is a synthetic DNA transposon designed to introduce precisely defined DNA sequences into the chromosomes of vertebrate animals for the purposes of introducing new traits and to discover new genes and their functions. It is a Tc1/mariner-type system, with the transposase resurrected from multiple inactive fish sequences.

Miniature Inverted-repeat Transposable Elements (MITEs) are a group of non-autonomous Class II transposable elements. Being non-autonomous, MITEs cannot code for their own transposase. They exist within the genomes of animals, plants, fungi, bacteria and even viruses. MITEs are generally short elements with terminal inverted repeats and two flanking target site duplications (TSDs). Like other transposons, MITEs are inserted predominantly in gene-rich regions and this can be a reason that they affect gene expression and play important roles in accelerating eukaryotic evolution. Their high copy number in spite of small sizes has been a topic of interest.

The PiggyBac (PB) transposon is a mobile genetic element that efficiently transposes between vectors and chromosomes via a "cut and paste" mechanism. During transposition, the PB transposase recognizes transposon-specific inverted terminal repeat sequences (ITRs) located on both ends of the transposon vector and efficiently moves the contents from the original sites and integrates them into TTAA chromosomal sites. The powerful activity of the PiggyBac transposon system enables genes of interest between the two ITRs in the PB vector to be easily mobilized into target genomes. The TTAA-specific transposon piggyBac is rapidly becoming a highly useful transposon for genetic engineering of a wide variety of species, particularly insects. They were discovered in 1989 by Malcolm Fraser at the University of Notre Dame.

Ac/Ds transposable controlling elements was the first transposable element system recognized in maize. The Ac Activator element is autonomous, whereas the Ds Dissociation element requires an Activator element to transpose. Ac was initially discovered as enabling a Ds element to break chromosomes. Both Ac and Ds can also insert into genes, causing mutants that may revert to normal on excision of the element. The phenotypic consequence of Ac/Ds transposable element includes mosaic colors in kernels and leaves in maize.

<span class="mw-page-title-main">Conservative transposition</span>

Transposition is the process by which a specific genetic sequence, known as a transposon, is moved from one location of the genome to another. Simple, or conservative transposition, is a non-replicative mode of transposition. That is, in conservative transposition the transposon is completely removed from the genome and reintegrated into a new, non-homologous locus, the same genetic sequence is conserved throughout the entire process. The site in which the transposon is reintegrated into the genome is called the target site. A target site can be in the same chromosome as the transposon or within a different chromosome. Conservative transposition uses the "cut-and-paste" mechanism driven by the catalytic activity of the enzyme transposase. Transposase acts like DNA scissors; it is an enzyme that cuts through double-stranded DNA to remove the transposon, then transfers and pastes it into a target site.

DNA transposons are DNA sequences, sometimes referred to "jumping genes", that can move and integrate to different locations within the genome. They are class II transposable elements (TEs) that move through a DNA intermediate, as opposed to class I TEs, retrotransposons, that move through an RNA intermediate. DNA transposons can move in the DNA of an organism via a single-or double-stranded DNA intermediate. DNA transposons have been found in both prokaryotic and eukaryotic organisms. They can make up a significant portion of an organism's genome, particularly in eukaryotes. In prokaryotes, TE's can facilitate the horizontal transfer of antibiotic resistance or other genes associated with virulence. After replicating and propagating in a host, all transposon copies become inactivated and are lost unless the transposon passes to a genome by starting a new life cycle with horizontal transfer. It is important to note that DNA transposons do not randomly insert themselves into the genome, but rather show preference for specific sites.

hAT transposons are a superfamily of DNA transposons, or Class II transposable elements, that are common in the genomes of plants, animals, and fungi.

References

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