Miniature Inverted-repeat Transposable Elements

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Miniature Inverted-repeat Transposable Elements (MITEs) are a group of non-autonomous Class II transposable elements (DNA sequences). Being non-autonomous, MITEs cannot code for their own transposase. They exist within the genomes of animals, plants, fungi, bacteria and even viruses. [1] [2] [3] [4] [5] [6] MITEs are generally short (50 to 500 bp) elements with terminal inverted repeats (TIRs; 10–15 bp) 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. [7] [8] Their high copy number in spite of small sizes has been a topic of interest.

Contents

Origin of MITEs

A detailed study of MITEs reveals that MITE subfamilies have arisen from related autonomous elements from a single genome and these subfamilies constitute the MITE families. One type of autonomous element can give rise to one or more MITE families. [9]

Classification

Based on their relations in sequences of TIRs with known TE superfamilies, MITEs have been classified into certain families. For example, wTourist, Acrobat, Hearthealer are MITE families in some plant species are under the TE superfamily PIF/Harbinger. Stowaway is a MITE family in Pisum sativum L. with TSD TA in relation to Tc1/mariner TE superfamily. A group of MITEs known as CMITES related to Piggybac superfamily were found in certain coral species. [10]

While most of the MITEs are grouped, some of them are yet to be allotted their TE superfamilies. Such families include AtATE in Arabidopsis thaliana and ATon family found in Aedes aegypti. Besides this, many more MITE families are likely to be discovered.

MITEs in Plant Genomes

MITEs were first discovered in plants. Elements belonging to the CACTA, hAT, Mutator, PIF, and Tc1/Mariner superfamilies have been described. [11] Depending upon the similarity of their terminal inverted repeats and target site duplications, most of the MITEs in plant genomes are divided into two major groups: Tourist-like MITEs (derived from PIF) [12] and Stowaway-like MITEs (derived from Tc1/mariner). [13] Stowaway and Tourist elements differ remarkably in their sequences. Still, they have been found to have significant structural similarities.

Stowaway elements possess target site specificity, have small size and conserved terminal inverted repeat. So is the case determined in Tourist like MITEs. They can form stable DNA secondary structures which can be very useful in identifying them. A few Stowaway elements also contain cis-acting regulatory domains.

Other MITE superfamilies have also been described in plants, such as hAT-type MITEs in banana [14] and the nightshades. [15]

MITEs as Genetic Markers

Based on the presence or absence of MITE family Heartbreaker (Hbr) in maize genome, a molecular marker was developed. These Hbr markers have been proved to be stable, uniformly distributed in maize genome. A study by Casa et al. showed that HBr markers could be used along with other molecular markers to study genotype of related maize inbred lines. [16]

Computational Assistance

Software like FINDMITE use sequence entries of some average sized bp to identify MITE families. A MATLAB-based program called detectMITE can detect MITEs on a genome wide scale and was tested on the rice genome. [17] Other tools like MUST and MITE-Hunter are also used for similar purposes. To characterize MITE families a toolkit has been developed called MITE Analysis Kit MAK by Yang and Hall. [18]

Related Research Articles

<span class="mw-page-title-main">Transposable element</span> Semiparasitic DNA sequence

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.

An inverted repeat is a single stranded sequence of nucleotides followed downstream by its reverse complement. The intervening sequence of nucleotides between the initial sequence and the reverse complement can be any length including zero. For example, 5'---TTACGnnnnnnCGTAA---3' is an inverted repeat sequence. When the intervening length is zero, the composite sequence is a palindromic sequence.

<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.

<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.

<span class="mw-page-title-main">Susan R. Wessler</span> American biologist

Susan Randi Wessler, ForMemRS, is an American plant molecular biologist and geneticist. She is Distinguished Professor of Genetics at the University of California, Riverside (UCR).

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.

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.

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.

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.

Transposon silencing is a form of transcriptional gene silencing targeting transposons. Transcriptional gene silencing is a product of histone modifications that prevent the transcription of a particular area of DNA. Transcriptional silencing of transposons is crucial to the maintenance of a genome. The “jumping” of transposons generates genomic instability and can cause extremely deleterious mutations. Transposable element insertions have been linked to many diseases including hemophilia, severe combined immunodeficiency, and predisposition to cancer. The silencing of transposons is therefore extremely critical in the germline in order to stop transposon mutations from developing and being passed on to the next generation. Additionally, these epigenetic defenses against transposons can be heritable. Studies in Drosophila, Arabidopsis thaliana, and mice all indicate that small interfering RNAs are responsible for transposon silencing. In animals, these siRNAS and piRNAs are most active in the gonads.

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.

Transposable elements are short strands of repetitive DNA that can self-replicate and translocate within the eukaryotic genome, and are generally perceived as parasitic in nature. Their transcription can lead to the production of dsRNAs, which resemble retroviruses transcripts. While most host cellular RNA has a singular, unpaired sense strand, dsRNA possesses sense and anti-sense transcripts paired together, and this difference in structure allows an host organism to detect dsRNA production, and thereby the presence of transposons. Plants lack distinct divisions between somatic cells and reproductive cells, and also have, generally, larger genomes than animals, making them an intriguing case-study kingdom to be used in attempting to better understand the epigenetics function of transposable elements.

<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.

Polintons are large DNA transposons which contain genes with homology to viral proteins and which are often found in eukaryotic genomes. They were first discovered in the mid-2000s and are the largest and most complex known DNA transposons. Polintons encode up to 10 individual proteins and derive their name from two key proteins, a DNA polymerase and a retroviral-like integrase.

Tc1/mariner is a class and superfamily of interspersed repeats DNA transposons. The elements of this class are found in all animals, including humans. They can also be found in protists and bacteria.

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

Transib is a superfamily of interspersed repeats DNA transposons. It was named after the Trans-Siberian Express. It is similar to EnSpm/CACTA.

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