Retrotransposon
Encyclopedia
Retrotransposons are genetic
elements that can amplify themselves in a genome
and are ubiquitous components of the DNA of many eukaryotic
organisms. They are a subclass of transposon
. They are particularly abundant in plants, where they are often a principal component of nuclear DNA
. In maize
, 49-78% of the genome is made up of retrotransposons. In wheat, about 90% of the genome consists of repeated sequences and 68% of transposable elements. In mammals, almost half the genome (45% to 48%) comprises transposons or remnants of transposons. Around 42% of the human genome is made up of retrotransposons while DNA transposons account for about 2-3%.
mode of transposition through an RNA intermediate increases the copy numbers of elements rapidly and thereby can increase genome
size. Like DNA transposable elements (class II transposons), retrotransposons can induce mutation
s by inserting
near or within genes. Furthermore, retrotransposon-induced mutations are relatively stable, because the sequence at the insertion site is retained as they transpose via the replication mechanism.
Retrotransposons copy themselves to RNA
and then back to DNA
that may integrate back to the genome. The second step of forming DNA may be carried out by a reverse transcriptase
which the retrotransposon encodes. Transposition and survival of retrotransposons within the host genome are possibly regulated both by retrotransposon- and host-encoded factors, to avoid deleterious effects on host and retrotransposon as well, in a relationship that has existed for many millions of years between retrotransposons and their plant hosts. The understanding of how retrotransposons and their hosts' genomes have co-evolved mechanisms to regulate transposition, insertion specificities, and mutational outcomes in order to optimize each other's survival is still in its infancy.
Most retrotransposons are very old and through accumulated mutations, are no longer able to retrotranspose.
(LTR) and the non-LTR retrotransposons.
) , Ty3-gypsy-like (Metaviridae
), and Pao-BEL-like groups based on both their degree of sequence similarity and the order of encoded gene products. Ty1-copia and Ty3-gypsy groups of retrotransposons are commonly found in high copy number (up to a few million copies per haploid nucleus
) in animals, fungi, protista, and plants genomes. Pao-BEL like elements have so far only been found in animals. About 8% of the human genome and approximately 10% of the mouse genome are composed of the LTR transposons.
to bryophytes, gymnosperms, and angiosperms.
s, which encode all the functions needed for retrotransposition. These functions include reverse transcriptase and endonuclease activities, in addition to a nucleic acid-binding property needed to form a ribonucleoprotein particle. SINEs on the other hand, co-opt the LINE machinery and function as nonautonomous retroelements.
promoter that resides inside the LINE. LINEs code for the enzyme reverse transcriptase
, and many LINEs also code for an endonuclease
(e.g. RNase H
). The reverse transcriptase has a higher specificity for the LINE RNA than other RNA, and makes a DNA copy of the RNA that can be integrated into the genome at a new site. The Endonuclease encoded by non-LTR retroposons may be AP (Apurinic/Pyrimidinic) type or REL (Restriction Endonuclease Like) type. R2 group of elements have REL type endonuclease which shows site specificty in insertion
The 5' UTR contains the promoter sequence, while the 3' UTR contains a polyadenylation signal (AATAAA) and a poly-A tail. Because LINEs move by copying themselves (instead of moving, like transposons do), they enlarge the genome. The human genome, for example, contains about 500,000 LINEs, which is roughly 17% of the genome. Of these, approximately 7,000 are full-length, a small subset of which are capable of retrotransposition.
Interestingly, it was recently found that specific LINE-1 retroposons in the human genome are actively transcribed and the associated LINE-1 RNAs are tightly bound to nucleosomes and essential in the establishment of local chromatin environment.
into tRNA, rRNA, and other small nuclear RNAs. SINEs do not encode a functional reverse transcriptase protein and rely on other mobile elements for transposition. The most common SINEs in primates are called Alu sequence
s. Alu elements are approximately 350 base pairs long, do not contain any coding sequences, and can be recognized by the restriction enzyme
AluI (hence the name). With about 1,500,000 copies, SINEs make up about 11% of the human genome. While historically viewed as "junk DNA", recent research suggests that in some rare cases both LINEs and SINEs were incorporated into novel genes, so as to evolve new functionality. The distribution of these elements has been implicated in some genetic diseases and cancers.
where the mobilized sequence may be found on bovine chromosome 15 in contig NW_001493315.1 nucleotides #1085432–1086142 and the originating sequence may be found on bovine chromosome 2 in contig NW_001501789.2 nucleotides #1096679–1097389. It is likely that similar composite transposons exist in other bovine genomic regions and other mammalian genomes. They could be detected with suitable algorithms.
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
elements that can amplify themselves in a genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
and are ubiquitous components of the DNA of many eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
organisms. They are a subclass of transposon
Transposon
Transposable elements are sequences of DNA that can move or transpose themselves to new positions within the genome of a single cell. The mechanism of transposition can be either "copy and paste" or "cut and paste". Transposition can create phenotypically significant mutations and alter the cell's...
. They are particularly abundant in plants, where they are often a principal component of nuclear DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. In maize
Maize
Maize known in many English-speaking countries as corn or mielie/mealie, is a grain domesticated by indigenous peoples in Mesoamerica in prehistoric times. The leafy stalk produces ears which contain seeds called kernels. Though technically a grain, maize kernels are used in cooking as a vegetable...
, 49-78% of the genome is made up of retrotransposons. In wheat, about 90% of the genome consists of repeated sequences and 68% of transposable elements. In mammals, almost half the genome (45% to 48%) comprises transposons or remnants of transposons. Around 42% of the human genome is made up of retrotransposons while DNA transposons account for about 2-3%.
Biological activity
The retrotransposons' replicativeDNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
mode of transposition through an RNA intermediate increases the copy numbers of elements rapidly and thereby can increase genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
size. Like DNA transposable elements (class II transposons), retrotransposons can induce mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s by inserting
Insertion (genetics)
In genetics, an insertion is the addition of one or more nucleotide base pairs into a DNA sequence. This can often happen in microsatellite regions due to the DNA polymerase slipping...
near or within genes. Furthermore, retrotransposon-induced mutations are relatively stable, because the sequence at the insertion site is retained as they transpose via the replication mechanism.
Retrotransposons copy themselves to RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
and then back to DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
that may integrate back to the genome. The second step of forming DNA may be carried out by a reverse transcriptase
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
which the retrotransposon encodes. Transposition and survival of retrotransposons within the host genome are possibly regulated both by retrotransposon- and host-encoded factors, to avoid deleterious effects on host and retrotransposon as well, in a relationship that has existed for many millions of years between retrotransposons and their plant hosts. The understanding of how retrotransposons and their hosts' genomes have co-evolved mechanisms to regulate transposition, insertion specificities, and mutational outcomes in order to optimize each other's survival is still in its infancy.
Most retrotransposons are very old and through accumulated mutations, are no longer able to retrotranspose.
Types of retrotransposons
Retrotransposons, also known as class I transposable elements, consist of two sub-types, the long terminal repeatLong terminal repeat
Long terminal repeats are sequences of DNA that repeat hundreds or thousands of times. They are found in retroviral DNA and in retrotransposons, flanking functional genes...
(LTR) and the non-LTR retrotransposons.
LTR retrotransposons
LTR retrotransposons have direct LTRs that range from ~100 bp to over 5 kb in size. LTR retrotransposons are further sub-classified into the Ty1-copia-like (PseudoviridaePseudoviridae
The Pseudoviridae are a family of viruses, including the following genera:*Genus Pseudovirus; type species: Saccharomyces cerevisiae Ty1 virus*Genus Hemivirus; type species: Drosophila melanogaster copia virus...
) , Ty3-gypsy-like (Metaviridae
Metaviridae
Metaviridae are a family of viruses which exist as retrotransposons in a eukaryotic host’s genome. They are very closely related to retroviruses: Metaviridae share many genomic elements with retroviruses, including length, organization, and genes themselves. This includes genes that encode reverse...
), and Pao-BEL-like groups based on both their degree of sequence similarity and the order of encoded gene products. Ty1-copia and Ty3-gypsy groups of retrotransposons are commonly found in high copy number (up to a few million copies per haploid nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
) in animals, fungi, protista, and plants genomes. Pao-BEL like elements have so far only been found in animals. About 8% of the human genome and approximately 10% of the mouse genome are composed of the LTR transposons.
Ty1-copia retrotransposons
Are abundant in species ranging from single-cell algaeAlgae
Algae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, such as the giant kelps that grow to 65 meters in length. They are photosynthetic like plants, and "simple" because their tissues are not organized into the many...
to bryophytes, gymnosperms, and angiosperms.
Ty3-gypsy retrotransposons
Are also widely distributed, including both gymnosperms and angiosperms.Non-LTR retrotransposons
consists of two sub-types, long interspersed elements (LINEs) and short interspersed elements (SINEs). They can also be found in high copy numbers (up to 250,000) in the plant species. Non-long terminal repeat (LTR) retroposons are widespread in eukaryotic genomes. LINEs possess two ORFOpen reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...
s, which encode all the functions needed for retrotransposition. These functions include reverse transcriptase and endonuclease activities, in addition to a nucleic acid-binding property needed to form a ribonucleoprotein particle. SINEs on the other hand, co-opt the LINE machinery and function as nonautonomous retroelements.
LINEs
Long INterspersed Elements are a group of genetic elements that are found in large numbers in eukaryotic genomes. They are transcribed (or are the evolutionary remains of what was once transcribed) to an RNA using an RNA polymerase IIRNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
promoter that resides inside the LINE. LINEs code for the enzyme reverse transcriptase
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
, and many LINEs also code for an endonuclease
Endonuclease
Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain, in contrast to exonucleases, which cleave phosphodiester bonds at the end of a polynucleotide chain. Typically, a restriction site will be a palindromic sequence four to six nucleotides long. Most...
(e.g. RNase H
RNase H
The enzyme RNase H is a non-specific endonuclease and catalyzes the cleavage of RNA via a hydrolytic mechanism. Members of the RNase H family can be found in nearly all organisms, from archaea to bacteria and eukaryota....
). The reverse transcriptase has a higher specificity for the LINE RNA than other RNA, and makes a DNA copy of the RNA that can be integrated into the genome at a new site. The Endonuclease encoded by non-LTR retroposons may be AP (Apurinic/Pyrimidinic) type or REL (Restriction Endonuclease Like) type. R2 group of elements have REL type endonuclease which shows site specificty in insertion
The 5' UTR contains the promoter sequence, while the 3' UTR contains a polyadenylation signal (AATAAA) and a poly-A tail. Because LINEs move by copying themselves (instead of moving, like transposons do), they enlarge the genome. The human genome, for example, contains about 500,000 LINEs, which is roughly 17% of the genome. Of these, approximately 7,000 are full-length, a small subset of which are capable of retrotransposition.
Interestingly, it was recently found that specific LINE-1 retroposons in the human genome are actively transcribed and the associated LINE-1 RNAs are tightly bound to nucleosomes and essential in the establishment of local chromatin environment.
SINEs
Short INterspersed Elements are short DNA sequences (<500 bases) that represent reverse-transcribed RNA molecules originally transcribed by RNA polymerase IIIRNA polymerase III
RNA polymerase III transcribes DNA to synthesize ribosomal 5S rRNA, tRNA and other small RNAs. The genes transcribed by RNA Pol III fall in the category of "housekeeping" genes whose expression is required in all cell types and most environmental conditions...
into tRNA, rRNA, and other small nuclear RNAs. SINEs do not encode a functional reverse transcriptase protein and rely on other mobile elements for transposition. The most common SINEs in primates are called Alu sequence
Alu sequence
An Alu element is a short stretch of DNA originally characterized by the action of the Alu restriction endonuclease. Alu elements of different kinds occur in large numbers in primate genomes. In fact, Alu elements are the most abundant mobile elements in the human genome. They are derived from the...
s. Alu elements are approximately 350 base pairs long, do not contain any coding sequences, and can be recognized by the restriction enzyme
Restriction enzyme
A Restriction Enzyme is an enzyme that cuts double-stranded DNA at specific recognition nucleotide sequences known as restriction sites. Such enzymes, found in bacteria and archaea, are thought to have evolved to provide a defense mechanism against invading viruses...
AluI (hence the name). With about 1,500,000 copies, SINEs make up about 11% of the human genome. While historically viewed as "junk DNA", recent research suggests that in some rare cases both LINEs and SINEs were incorporated into novel genes, so as to evolve new functionality. The distribution of these elements has been implicated in some genetic diseases and cancers.
Composite SINE Transposons
Two SINEs may act in concert to flank and mobilize an intervening single copy DNA sequence. This was reported for a 710 bp DNA sequence upstream of the bovine beta globin gene. The DNA arrangement forms a composite transposon whose presence has been confirmed by the complete bovine genomic sequenceBovine genome
75px|left|The genome of a female Hereford cow has been sequenced by the Bovine Genome Sequencing and Analysis Consortium, a team of researchers led by the National Institutes of Health and the U.S...
where the mobilized sequence may be found on bovine chromosome 15 in contig NW_001493315.1 nucleotides #1085432–1086142 and the originating sequence may be found on bovine chromosome 2 in contig NW_001501789.2 nucleotides #1096679–1097389. It is likely that similar composite transposons exist in other bovine genomic regions and other mammalian genomes. They could be detected with suitable algorithms.
See also
- Endogenous retrovirusEndogenous retrovirusEndogenous retroviruses are sequences in the genome thought to be derived from ancient viral infections of germ cells in humans, mammals and other vertebrates; as such their proviruses are passed on to the next generation and now remain in the genome....
- TransposonTransposonTransposable elements are sequences of DNA that can move or transpose themselves to new positions within the genome of a single cell. The mechanism of transposition can be either "copy and paste" or "cut and paste". Transposition can create phenotypically significant mutations and alter the cell's...
- Genomic organizationGenomic organizationright|thumb|300px|Genome sizes and corresponding composition of six major model organisms as pie charts. The increase in [[genome]] size correlates with the vast expansion of noncoding and repeat [[DNA]] sequences in more complex...
- Interspersed repeatInterspersed repeatInterspersed repetitive DNA is found in all eukaryotic genomes. Certain classes of these sequences propagate themselves by RNA mediated transposition, and they have been called retrotransposons. Interspersed repetitive DNA elements allow new genes to evolve. They do this by uncoupling similar DNA...
- Retrotransposon markerRetrotransposon MarkerRetrotransposon markers are retrotransposons that are used as cladistic markers.The analysis of SINEs – Short INterspersed Elements – LINEs – Long INterspersed Elements – or truncated LTRs – Long Terminal Repeats – as molecular cladistic markers represents a particularly interesting complement to...
s, a powerful method of reconstructing phylogenies. - RetrOryzaRetrOryzaRetrOryza is a database of Long terminal repeat-retrotransposons for the rice genome....