Short Interspersed Elements (SINEs)/Alu Types and Distribution

The most populous retrotransposons in the human genome are LINEs (Long INterspersed Elements) and SINEs (Short INterspersed Elements). Retroelements are classified into two classes: those that contain Long Terminal Repeats (LTRs) and those that lack them (non-LTR retrotransposons). The human genome contains different families of non-LTR retrotransposons with L1 elements accounting for about 17% of the genome by mass. Most of the non-autonomous, non-LTR retrotransposons fall into a general class, termed SINEs that are derived from RNA polymerase III transcripts. There are many different types of SINEs; however, Alu elements are present at greater than 1 million copies in the human genome and comprise ~11% of human DNA. Alu elements are a dimeric 300bp unit, composed of two non-identical units or arms joined in the middle by an adenosine (A)-rich linker. Each Alu repeat also ends with an A-rich tail and is flanked by short direct repeat sequences. Alu elements are thought to have originated from the 7SL RNA gene, a component of the signal recognition particle (SRP). Alu elements are restricted to primate genomes and thought to have arisen as a repeated DNA sequence family about 65 million years ago.

The evolution of Alu elements is dependent on their mechanism of amplification. Several lines of evidence suggest that Alu elements depend on the endonuclease and reverse transcriptase activities provided in trans by L1 elements. Alu elements started to amplify 65 million years ago with a peak in amplification between 60 and 35 million years ago. It is estimated that there is one Alu insertion in every 20 births, a rate that is approximately two orders of magnitude less than the estimated peak.

The amplification of Alu elements has had both positive and negative impacts on primate genomes. The major negative impact on the genome involves insertion mutagenesis or Alu element mediated recombination. These two mechanisms account for 0.4% of all human genetic disorders. In humans, the insertion of human-specific Alu elements such as the Yb8 family has been responsible for the inactivation of certain genes (e.g. CMAH). Alu element mediated recombination has caused both germ-line (e.g. familial hypercholesterolemia) and somatic (various cancers) disorders, and has altered the architecture of primate genomes throughout time. On occasion, Alu elements have also positively impacted the human genome. For example, individual Alu elements can introduce polyadenylation signals and/or alternative splice sites into genes, which can lead to the exonization of the Alu element.