An Alu sequence is a short stretch of DNA originally characterized by the action of the Alu restriction endonuclease. Alu sequences of different kinds occur in large numbers in primate genomes. In fact, Alu sequences are the most abundant mobile elements in the human genome. They are derived from the small cytoplasmic 7SL RNA, a component of the signal recognition particle. The event, when a copy of the 7SL RNA became a precursor of the Alu sequence, took place in the genome of an ancestor of Supraprimates[1].
Alu insertions have been implicated in several inherited human diseases and in various forms of cancer.
The study of Alu sequences has also been important in elucidating human population genetics and the evolution of primates, including the evolution of humans. The Alu endonuclease is so-named because it was isolated from Arthrobacter luteus.
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The Alu family
The Alu family is a family of repetitive elements in the Human genome. Alu sequences are about 300 base pairs long and are therefore classified as short interspersed elements (SINEs) amongst the class of repetitive DNA elements.
There are over one million Alu sequences interspersed throughout the human genome, and it is estimated that about 10.7% of the human genome consists of Alu sequences. However less than 0.5% are polymorphic[2]. In 1988 Alu sequences were split in two major subfamilies known as AluJ and AluS, and numerous sub-subfamilies. Later on, a sub-subfamily of AluS which included active Alu elements was given a separate name AluY. The discovery of Alu subfamilies led to the hypothesis of master/source genes, and provided the definitive link between transposable elements (active elements) and interspersed repetitive DNA (mutated copies of active elements).
The recognition sequence of the Alu endonuclease is 5' AG/CT 3'; that is, the enzyme cuts the DNA segment between the guanine and cytosine residues.
Alu sequences are retrotransposons and look like DNA copies made from RNA polymerase III-encoded RNAs. Alu elements do not encode for protein products and depend on LINE retrotransposons for their replication.[3]
Alu sequences in primates form a fossil record that is relatively easy to decipher because Alu sequence insertion events have a characteristic signature that is both easy to read and faithfully recorded in the genome from generation to generation. The study of Alu sequences thus reveals details of ancestry because individuals will only share a particular Alu sequence insertion if they have a common ancestor.
Most human Alu sequence insertions can be found in the corresponding positions in the genomes of other primates, but about 7,000 Alu insertions are unique to humans[4].
Alu insertions and human disease
Alu insertions are sometimes disruptive and can result in inherited disorders. However, most Alu insertions act as markers that segregate with the disease so the presence of a particular Alu allele does not mean that the carrier will definitely get the disease. The first report of Alu-mediated recombination causing a prevalent inherited predisposition to cancer was a 1995 report about hereditary nonpolyposis colorectal cancer.[5]
The following human diseases have been linked with Alu insertions:[6]
- Breast cancer
- Ewing's sarcoma
- Familial hypercholesterolemia
- Hemophilia
- Neurofibromatosis
- Diabetes mellitus type II
References
- ^ Kriegs JO, Churakov G, Jurka J, Brosius J, Schmitz J (April 2007). "Evolutionary history of 7SL RNA-derived SINEs in Supraprimates". Trends Genet. 23 (4): 158–61. doi:. PMID 17307271.
- ^ Roy-Engel AM, Carroll ML, Vogel E, et al. (September 2001). "Alu insertion polymorphisms for the study of human genomic diversity". Genetics 159 (1): 279–90. PMID 11560904.
- ^ Kramerov DA, Vassetzky NS (2005). "Short retroposons in eukaryotic genomes". Int. Rev. Cytol. 247: 165–221. doi:. PMID 16344113.
- ^ And Analysis Consortium, The Chimpanzee Sequencing (September 2005). "Initial sequence of the chimpanzee genome and comparison with the human genome". Nature 437 (7055): 69–87. doi:. PMID 16136131. http://www.nature.com/nature/journal/v437/n7055/full/nature04072.html.
- ^ Nyström-Lahti M, Kristo P, Nicolaides NC, et al. (November 1995). "Founding mutations and Alu-mediated recombination in hereditary colon cancer". Nat. Med. 1 (11): 1203–6. doi:. PMID 7584997.
- ^ Batzer MA, Deininger PL (May 2002). "Alu repeats and human genomic diversity". Nat. Rev. Genet. 3 (5): 370–9. doi:. PMID 11988762. http://batzerlab.lsu.edu/Publications/Batzer%20and%20Deininger%202002%20Nature%20Reviews%20Genetics.pdf.
External links
- MeSH Alu+Repetitive+Sequences
- AF-1(Alu Finder):A web server to find Alu elements in primate genomes.
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