An Alu sequence is a short stretch of DNA 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. Alu insertions have been implicated in several inherited human diseases, including various forms of cancer, as discussed later in this article.
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.
The Alu family
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 1 million Alu sequences interspersed throughout the human genome, and it is estimated that about 10% of the mass of the human genome consists of Alu sequences. However less than 0.5% are polymorphic [Roy_Engel 2001].
The recognition sequence of the Alu endonuclease is 5' AG/CT 3'; that is, the enzyme splits the DNA segment between the guanine and cytosine.
Alu sequences are retrotransposons and look like DNA copies of mRNA.
The Alu fossil record
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 2,000 Alu insertions are unique to humans.
Alu insertions and human disease
Alu insertions are sometimes disruptive and can result in inherited disorders.
The first report of Alu-mediated recombination causing a prevalent, inherited predisposition to cancer was a 1995 report about hereditary nonpolyposis colorectal cancer [Nystrom-Lahti].
In the review article referenced below [Batzer 2002], the authors report that the following human diseases have been linked with Alu insertions:
- A. Roy-Engel et al. Alu Insertion Polymorphisms for the Study of Human Genomic Diversity. Genetics 159: 279–290 (September 2001).
- M. A. Batzer and P. L. Deininger. Alu Repeats and Human Genomic Diversity. Nature Reviews: Genetics 3: 370-9 (May 2002) (http://batzerlab.lsu.edu/Publications/Batzer%20and%20Deininger%202002%20Nature%20Reviews%20Genetics.pdf)
- M. Nystrom-Lahti et al. Founding mutations and Alu-mediated recombination in hereditary colon cancer. Nat Med. 1995 Nov;1(11):1203-6