Evolution of Human Retrosequences: Alu

Abstract

Throughout evolution, mobile elements have accumulated to high copy numbers contributing to almost half of the human genomic mass. Evidence indicates that only the retroelements are currently active. In humans, the short interspersed elements (SINE), Alu, with over one million copies, outnumbers any of the other types of retroelements. Alu arose from the dimerization of modified 7SL RNA (ribonucleic acid) pseudogenes early in primate evolution, where different subfamilies continued to amplify during particular periods. Alu amplification has both positively and negatively impacted the human genome, and continues to play an important role in its shaping as a contributor of genetic instability and variation.

Keywords: SINE; LINE; ALU; evolution; mobile element

Figure 1.

Basic schematics of classes of retroelements. Retroviruses are flanked by long terminal repeats (LTR) sequences (black boxes with white arrows) that contain a strong promoter and a ‘Hogness box’ (H). Retroviruses all have open reading frames (ORFs) that code for three essential genes: gag, pol and env, although they may have other genes as well. LTR retrotransposons are also flanked by LTRs and contain the equivalent of gag and pol genes. The non‐LTR retrotransposons or LINE‐like elements contain an RNA polymerase II promoter, two ORFs and a variable poly A tail. In the human LINE, L1, ORF 1 codes for an RNA‐binding protein, while ORF2 codes for a protein with endonuclease and reverse transcriptase activity. The nonautonomous retroposons or SINEs have an internal pol III promoter (A & B box) flanked at the 3′ end by a variable A‐rich tail. The SVA retroposons are a composite of sequences from different sources: a hexameric repeat region, two antisense Alu fragments, a variable number tandem repeat region (VNTR) and SINE‐R. Retropseudogenes, or processed pseudogenes, arise from reverse transcription of spliced mRNAs of transcribed genes. They are characterized by an absence of a 5′ promoter and introns, and the presence of flanking direct (black arrows) repeats and a poly A segment. Diagram is not drawn to scale.

Figure 2.

Origin of Alu elements. Alu elements are thought to have arisen from a processed 7SL RNA giving rise to the ancestral element: fossil Alu monomer (FAM). FAM evolved to the FLA monomer and the free right Alu (FRA) monomer families with sequence variations between each other. The first progenitor of the Alu dimeric family possibly arose through the fusion of FLA and FRA monomers. The left monomer contains the internal pol III promoter with the A and B boxes. The Alu RNA contains monomers are separated by an A‐rich region and the 3′ flank contains a poly A tract.

Figure 3.

Evolutionary tree of the Alu subfamilies and amplification rates throughout the primate radiation. The old Alu subfamilies J, Sx and Sg1 were most active around 35–55 mya (indicated at the right) giving rise to the majority of the Alu elements present today in the human genome. Boxed areas represent the potential period of maximum activity for each Alu subfamily. The amplification rate of Alu decreased with evolutionary time as observed by the reduction of the copy numbers (indicated at the left). Currently the young Alu subfamilies (Y, Ya5, Yb8, Ya5, Ya5a2 and Yc1) contribute to all the known polymorphisms in the human genome.

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Further Reading

Batzer MA, Deininger PL, Hellmann‐Blumberg U et al. (1996) Standardized nomenclature for Alu repeats. Journal of Molecular Evolution 42: 3–6.

Deininger P and Batzer M (1995) SINE master genes and population biology. In: Maraia R (ed.) The Impact of Short, Interspersed Elements (SINEs) on the Host Genome, pp. 43–60. Georgetown, TX: R.G. Landes.

Deininger PL, Moran JV, Batzer MA and Kazazian HH (2003) Mobile elements and mammalian genome evolution. Current Opinion in Genetics & Development 13: 651–658.

Kapitonov V and Jurka J (1996) The age of Alu subfamilies. Journal of Molecular Evolution 42: 59–65.

Malik HS, Burke WD and Eickbush TH (1999) The age and evolution of non‐LTR retrotransposable elements. Molecular Biology and Evolution 16: 793–805.

Roy‐Engel AM (2004) Dynamics of SINE amplification. In: Parisi V, DeFonzo V and Aluffi‐Pentini F (eds) Dynamical Genetics, pp. 301–318. Kerala, India: Research Signpost.

Schmid CW (1998) Does SINE evolution preclude Alu function? Nucleic Acids Research 26: 4541–4550.

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Roy‐Engel, Astrid M, Batzer, Mark A, and Deininger, Prescott L(Mar 2008) Evolution of Human Retrosequences: Alu. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005131.pub2]