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.

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.

Tn10 is a transposable element, which is a sequence of DNA that is capable of mediating its own movement from one position in the DNA of the host organism to another. There are a number of different transposition mechanisms in nature, but Tn10 uses the non-replicative cut-and-paste mechanism. The transposase protein recognizes the ends of the element and cuts it from the original locus. The protein-DNA complex then diffuses away from the donor site until random collisions brings it in contact with a new target site, where it is integrated. To accomplish this reaction the 50 kDa transposase protein must break four DNA strands to free the transposon from the donor site, and perform two strand exchange reactions to integrate the element at the target site. This leaves two strands unjoined at the target site, but the host DNA repair proteins take care of this. The target site selection is essentially random, but there is a preference for the sequence 5'-GCTNAGC-3'. The 6-9 base pairs that flank the sequence also influence selection of the insertion site.

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

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<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.

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

Pogo transposable element with ZNF domain is a protein that in humans is encoded by the POGZ gene.

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

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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 system employs a genetically engineered transposase enzyme to insert a gene into a cell's genome. It is built upon the natural PiggyBac (PB) transposable element (transposon), enabling the back and forth movement of genes between chromosomes and genetic vectors such as plasmids through 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.

<span class="mw-page-title-main">PiggyBac Transposable Element Derived 5</span> Protein-coding gene in the species Homo sapiens

PiggyBac Transposable Element Derived 5 is an enzyme that in humans is encoded by the PGBD5 gene. PGBD5 is a DNA transposase related to the ancient PiggyBac transposase first identified in the cabbage looper moth, Trichoplusia ni. The gene is believed to have been domesticated over 500 million years ago in the common ancestor of cephalochordates and vertebrates. The putative catalytic triad of the protein composed of three aspartic acid residues is conserved among PGBD5-like genes through evolution, and is distinct from other PiggyBac-like genes. PGBD5 has been shown to be able to transpose DNA in a sequence-specific, cut-and-paste fashion. PGBD5 has also been proposed to mediate site-specific DNA rearrangements in human tumors.

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

  1. ↑ Plasterk, Ronald H.A; Izsvák, Zsuzsanna; Ivics, Zoltán (1999). "Resident aliens: The Tc1/mariner superfamily of transposable elements". Trends in Genetics. 15 (8): 326–32. doi:10.1016/S0168-9525(99)01777-1. PMID   10431195.
  2. ↑ Robertson, H.M. (1995). "The Tc1-mariner superfamily of transposons in animals". J. Insect Physiol. 41 (2): 99–105. doi:10.1016/0022-1910(94)00082-r.
  3. ↑ Bradic, Martina; Warring, Sally D; Low, Vivien; Carlton, Jane M (2014). "The Tc1/mariner transposable element family shapes genetic variation and gene expression in the protist Trichomonas vaginalis". Mobile DNA. 5: 12. doi: 10.1186/1759-8753-5-12 . PMC   4021607 . PMID   24834134.
  4. 1 2 Capy, Pierre; Langin, Thierry; Higuet, Dominique; Maurer, Patricia; Bazin, Claude (1997). "Do the integrases of LTR-retrotransposons and class II element transposases have a common ancestor?". Genetica. 100 (1/3): 63–72. doi:10.1023/A:1018300721953. PMID   9440259. S2CID   24866580.
  5. 1 2 Walter, Marius (2016). Transposon regulation upon dynamic loss of DNA methylation (Thesis). Université Pierre et Marie Curie. doi:10.13140/rg.2.2.18747.21286.
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  9. ↑ Rosenzweig, B; Liao, L. W.; Hirsh, D (1983). "Sequence of the C. Elegans transposable element Tc1". Nucleic Acids Research. 11 (12): 4201–4209. doi:10.1093/nar/11.12.4201. PMC   326035 . PMID   6306578.
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  17. ↑ Lampe DJ, Witherspoon DJ, Soto-Adames FN, Robertson HM (April 2003). "Recent horizontal transfer of mellifera subfamily mariner transposons into insect lineages representing four different orders shows that selection acts only during horizontal transfer". Mol. Biol. Evol. 20 (4): 554–62. doi: 10.1093/molbev/msg069 . PMID   12654937.
  18. ↑ Mandal PK, Kazazian HH (October 2008). "SnapShot: Vertebrate transposons". Cell. 135 (1): 192–192.e1. doi: 10.1016/j.cell.2008.09.028 . PMID   18854165. S2CID   82147.
  19. ↑ Carlton JM, Hirt RP, Silva JC, et al. (January 2007). "Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis". Science. 315 (5809): 207–12. Bibcode:2007Sci...315..207C. doi:10.1126/science.1132894. PMC   2080659 . PMID   17218520.
  20. ↑ Miskey, C.; Papp, B.; Mates, L.; Sinzelle, L.; Keller, H.; Izsvak, Z.; Ivics, Z. (2 April 2007). "The Ancient mariner Sails Again: Transposition of the Human Hsmar1 Element by a Reconstructed Transposase and Activities of the SETMAR Protein on Transposon Ends". Molecular and Cellular Biology. 27 (12): 4589–4600. doi:10.1128/MCB.02027-06. PMC   1900042 . PMID   17403897.
  21. ↑ Gil, Estel; Bosch, Assumpcio; Lampe, David; Lizcano, Jose M.; Perales, Jose C.; Danos, Olivier; Chillon, Miguel; Cordaux, Richard (11 September 2013). "Functional Characterization of the Human Mariner Transposon Hsmar2" (PDF). PLOS ONE. 8 (9): e73227. Bibcode:2013PLoSO...873227G. doi: 10.1371/journal.pone.0073227 . PMC   3770610 . PMID   24039890.
  22. ↑ Hartl, D (2001). "Discovery of the transposable element mariner". Genetics. 157 (2): 471–476. doi:10.1093/genetics/157.2.471. PMC   1461507 . PMID   11156971.
  23. ↑ Lampe, D. J.; Akerley, B. J.; Rubin, E. J.; Mekalanos, J. J.; Robertson, H. M. (1999). "Hyperactive transposase mutants of the Himar1 mariner transposon". Proceedings of the National Academy of Sciences. 96 (20): 11428–11433. Bibcode:1999PNAS...9611428L. doi: 10.1073/pnas.96.20.11428 . PMC   18050 . PMID   10500193.
  24. ↑ Gomulski, LM; Torti, C; Bonizzoni, M; Moralli, D; Raimondi, E; Capy, P; Gasperi, G; Malacrida, AR (December 2001). "A new basal subfamily of mariner elements in Ceratitis rosa and other tephritid flies". Journal of Molecular Evolution. 53 (6): 597–606. Bibcode:2001JMolE..53..597G. doi:10.1007/s002390010246. PMID   11677619. S2CID   21289272.
  25. ↑ Shao, H; Tu, Z (November 2001). "Expanding the diversity of the IS630-Tc1-mariner superfamily: discovery of a unique DD37E transposon and reclassification of the DD37D and DD39D transposons". Genetics. 159 (3): 1103–15. doi:10.1093/genetics/159.3.1103. PMC   1461862 . PMID   11729156.
  26. ↑ Smit, AF; Riggs, AD (20 February 1996). "Tiggers and DNA transposon fossils in the human genome". Proceedings of the National Academy of Sciences of the United States of America. 93 (4): 1443–8. doi: 10.1073/pnas.93.4.1443 . PMC   39958 . PMID   8643651.
  27. ↑ Casola, C; Hucks, D; Feschotte, C (January 2008). "Convergent domestication of pogo-like transposases into centromere-binding proteins in fission yeast and mammals". Molecular Biology and Evolution. 25 (1): 29–41. doi:10.1093/molbev/msm221. PMC   2268608 . PMID   17940212.
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