Retrotransposon

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 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 retrotransposonsSanMiguel, Phillip and Jeffrey L. Bennetzen (1998) Evidence that a recent increase in maize genome size was caused by the massive amplification of intergene retrotranposons. Annals of Botany 82 (supplement A): 37-44. [http://aob.oxfordjournals.org/cgi/reprint/82/suppl_1/37.pdf] ] . In wheat, about 90% of the genome consists of repeated sequences and 68% of transposable elementsLi W, Zhang P, Fellers JP, Friebe B, and Gill BS (2004) Sequence composition, organization and evolution of the core Triticeae genome. Plant J. 40: 500-511. [http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-313X.2004.02228.x] ] . 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%Lander ES, Linton LM, Birren B, Nusbaum C, et al. Initial sequencing and analysis of the human genome. [http://www.nature.com/nature/journal/v409/n6822/full/409860a0.html Nature, 2001; 409(6822): 860-921] ] .

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

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 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 animalsCopeland CS, Mann VH, Morales ME, Kalinna BH, Brindley PJ. The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements. BMC Evol Biol. 2005 Feb 23;5(1):20.] Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, Chalhoub B, Flavell A, Leroy P, Morgante M, Panaud O, Paux E, SanMiguel P, Schulman AH. A unified classification system for eukaryotic transposable elements.Nat Rev Genet. 2007 Dec;8(12):973-82.] . About 10% of the human genome and approximately 8% of the mouse genome are composed of the LTR transposons. [http://genomebiology.com/2004/5/3/R14]

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.

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 250,000Fact|date=February 2007) in the plant species.

promoter sequence, while the 3' UTR contains a polyadenylation signal (AATAAA) and a poly-A tail.Deininger PL, Batzer MA. Mammalian retroelements. Genome Research. 2002;12(10):1455–1465.] 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.Pierce, B. A. (2005). Genetics: A conceptual approach. Freeman. Page 311.] LINEs are used to generate genetic fingerprints.

INEs

Short interspersed nuclear elements are short DNA sequences (<500 basesKing, Robert C. and William D. Stansfield (1997). A Dictionary of Genetics. Fifth Edition. Oxford University Press.] ) 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.Pierce, B. A. (2005). Genetics: A conceptual approach. Freeman. Page 311.] 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 levelscite journal |last = Santangelo| first = Andrea | coauthors = de Souza, Flavio; Franchini, Lucia; Bumaschny, Viviana; Low, Malcolm; Rubinstein,Marcelo|title = Ancient Exaptation of a CORE-SINE Retroposon into a Highly Conserved Mammalian Neuronal Enhancer of the Proopiomelanocortin Gene| journal = PLoS Genetics | volume =3 | issue = 10|publisher = Public Library of Science| date = 2007-10|url = http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pgen.0030166 | doi = 10.1371/journal.pgen.0030166 | accessdate = 2007-12-31 |pages = e166] . 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.

ee also

*Endogenous retrovirus
*Transposon
*Genomic organization
*Interspersed repeat
*Retrotransposon markers, a powerful method of reconstructing phylogenies.

References