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^[1]. In wheat, about 90% of the genome consists of repeated sequences and 68% of transposable elements^[2]. 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%^[3]. This translates to millions of elements, so that on average, every gene in our genome contains around 3 retrotransposons.

Biological activity

The retrotransposons' replicative 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 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, via reverse transcriptase, back to DNA. 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 repeat (LTR) and the non-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 (Pseudoviridae) and the Ty3-gypsy-like (Metaviridae) 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 plants with large genomes.

Ty1-copia retrotransposons

are abundant in species ranging from single-cell algae to bryophytes, gymnosperms, and angiosperms.

Ty3-gypsy retrotransposons

are also widely distributed, including both gymnosperms and angiosperms.

LTR retrotransposons make up approximately 8% of the human genome^[3].

Non-LTR retrotransposons

consists of two sub-types, long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). They can also be found in high copy numbers (up to 250,000) in the plant species.

LINEs

Long interspersed nuclear elements are long DNA sequences (>5kb^[5]) that represent reverse-transcribed RNA molecules originally transcribed by RNA polymerase II into mRNA (messenger RNA to be translated into protein on ribosomes). LINE elements code for 2 proteins; one that has the ability to bind single stranded RNA, and another that has known reverse transcriptase and endonuclease activity, enabling them to copy both themselves and noncoding SINES such as Alu elements (see below for more detail). A typical LINE contains a 5'UTR (untranslated region) 2 ORFs (open reading frames) and a 3'UTR. The 5'UTR contains an internal polymerase II promoter sequence, while the 3'UTR contains a polyadenylation signal (AATAAA) and a poly-A tail.^[6] Because LINES move by copying themselves (instead of moving, like transposons do), they enlarge the genome. The human genome, for example, contains about 900,000 LINES, which is roughly 21% of the genome.^[7] LINES are used to generate genetic fingerprints.

SINEs

Short interspersed nuclear elements are short DNA sequences (<500 bases^[5]) that represent reverse-transcribed RNA molecules originally transcribed by RNA polymerase III 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 sequences. Alu elements are 280 base pairs long, do not contain any coding sequences, and can be recognized by the restriction enzyme AluI (thus the name). With about 1 million copies, SINEs make up about 13% of the human genome.^[7] While previously believed to be "junk DNA", recent research suggests that both LINEs and SINEs have a significant role in gene evolution, structure and transcription levels. The distribution of these elements has been implicated in some genetic diseases and cancers.

Retroviruses, like HIV-1 or HTLV-1 behave like retrotransposons and contain both reverse transcriptase and integrase. The integrase is the retrotransposon equivalent of the transposase of DNA-transposons.

See also

• Transposon
• Genomic organization
• Interspersed repeat
• Retrotransposon markers, a powerful method of reconstructing phylogenies.

References