Retrotransposons (also called transposons via RNA intermediates) are genetic elements that can amplify themselves in a genome and are ubiquitous components of the DNA of many eukaryotic organisms. They are one of the two subclasses of transposon, where the other is DNA transposon, which does not involve an RNA intermediate. 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%) is transposons or remnants of transposons. Around 42% of the human genome is made up of retrotransposons, while DNA transposons account for about 2–3%.
The retrotransposons' replicative mode of transposition by means of an RNA intermediate rapidly increases the copy numbers of elements and thereby can increase genome size. Like DNA transposable elements (class II transposons), retrotransposons can induce mutations 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 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.
Because of accumulated mutations, most retrotransposons are no longer able to retrotranspose.
Retrotransposons, also known as class I transposable elements, consist of two subclasses, the long terminal repeat (LTR) and the non-LTR retrotransposons. Classification into these subclasses is based on the phylogeny of the reverse transcriptase, which goes in line with structural differences, such as presence/absence of long terminal repeats as well as number and types of open reading frames, encoding domains and target site duplication lengths.
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 (Pseudoviridae), Ty3-gypsy-like (Metaviridae), and BEL-Pao-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. BEL-Pao like elements have so far only been found in animals. Although Retroviruses are often classified separately, they share many features with LTR retrotransposons. A major difference with Ty1-copia and Ty3-gypsy retrotransposons is that retroviruses have an Envelope protein (ENV). A retrovirus can be transformed into an LTR retrotransposon through inactivation or deletion of the domains that enable extracellular mobility. If such a retrovirus infects and subsequently inserts itself in the genome in germ line cells, it may become transmitted vertically and become an Endogenous Retrovirus (ERV). Endogenous retroviruses make up about 8% of the human genome and approximately 10% of the mouse genome.
In plant genomes, LTR retrotransposons are the major repetitive sequence class, e.g. able to constitute more than 75% of the maize genome.
Ty1-copia retrotransposons are abundant in species ranging from single-cell algae to bryophytes, gymnosperms, and angiosperms. They encode four protein domains in the following order: protease, integrase, reverse transcriptase, and ribonuclease H.
At least two classification systems exist for the subdivision of Ty1-copia retrotransposons into five lineages: Sireviruses/Maximus, Oryco/Ivana, Retrofit/Ale, TORK (subdivided in Angela/Sto, TAR/Fourf, GMR/Tork), and Bianca.
Sireviruses/Maximus retrotransposons contain an additional putative envelope gene. This lineage is named for the founder element SIRE1 in the Glycine max genome, and was later described in many species such as Zea mays, Arabidopsis thaliana, Beta vulgaris, and Pinus pinaster. Plant Sireviruses of many sequenced plant genomes are summarized at the MASIVEdb Sirevirus database.
Ty3-gypsy retrotransposons (Metaviridae) are widely distributed in the plant kingdom, including both gymnosperms and angiosperms. They encode at least four protein domains in the order: protease, reverse transcriptase, ribonuclease H, and integrase. Based on structure, presence/absence of specific protein domains, and conserved protein sequence motifs, they can be subdivided into several lineages:
Errantiviruses contain an additional defective envelope ORF with similarities to the retroviral envelope gene. First described as Athila-elements in Arabidopsis thaliana, they have been later identified in many species, such as Glycine max  and Beta vulgaris.
Chromoviruses contain an additional chromodomain (chromatin organization modifier domain) at the C-terminus of their integrase protein. They are widespread in plants and fungi, probably retaining protein domains during evolution of these two kingdoms. It is thought that the chromodomain directs retrotransposon integration to specific target sites. According to sequence and structure of the chromodomain, chromoviruses are subdivided into the four clades CRM, Tekay, Reina and Galadriel. Chromoviruses from each clade show distinctive integration patterns, e.g. into centromeres or into the rRNA genes.
Metaviruses describe conventional Ty3-gypsy retrotransposons that do not contain additional domains or ORFs.
Endogenous retroviruses are the most important LTR retrotransposons in mammals, including human where the Human ERVs make up 8% of the genome.
Non-LTR retrotransposons consist of two sub-types, long interspersed elements (LINEs) and short interspersed elements (SINEs). They can also be found in high copy numbers, as shown in the plant species. Non-long terminal repeat (LTR) retroposons are widespread in eukaryotic genomes. LINEs possess two ORFs, 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.
Long Interspersed Nuclear Elements (LINE) are a group of genetic elements that are found in large numbers in eukaryotic genomes, comprising 17% of the human genome (99.9% of which is no longer capable of mobilization). Among the LINE, there are several subgroups, such as L1, L2 and L3. Human coding L1 begin with an untranslated region (UTR) that includes an RNA polymerase II promoter, two non-overlapping open reading frames (ORF1 and ORF2), and ends with another UTR. Recently, a new open reading frame in the 5' end of the LINE elements has been identified in the reverse strand. It is shown to be transcribed and endogenous proteins are observed. The name ORF0 is coined due to its position with respect to ORF1 and ORF2. ORF1 encodes an RNA binding protein and ORF2 encodes a protein having an endonuclease (e.g. RNase H) as well as a reverse transcriptase. 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. Elements in the R2 group have REL type endonuclease, which shows site specificity 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 (and other class I transposons, e.g. LTR retrotransposons and SINEs) move by copying themselves (instead of moving by a cut and paste like mechanism, as class II 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.
Short Interspersed Nuclear Elements are short DNA sequences (<500 bases) that represent reverse-transcribed RNA molecules originally transcribed by RNA polymerase III into tRNA, 5S ribosomal RNA, and other small nuclear RNAs. The mechanism of retrotransposition of these elements is more complicated than LINEs, and less dependent solely on the actual elements that they encode. SINEs do not encode a functional reverse transcriptase protein and rely on other mobile elements for transposition. In some cases they may have their own endonuclease that will allow them to cleave their way into the genome, but the majority of SINEs integrate at chromosomal breaks by using random DNA breaks to prime reverse transcriptase.
The most common SINEs in primates are called Alu sequences. 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. Although sequence analysis of human Alu subfamilies shows the existence of mosaic (recombinant) elements, experimental evidence is lacking. In the primitive eukaryote Entamoeba histolytica, the frequent exchange of sequence during retrotransposition has been reported; this results in a mosaic pattern in its SINE sequences