A significant fraction of many vertebrate chromosomes is made up of repeated DNA sequences. In human chromosomes, these repeats are mostly mutated and truncated versions of nonretroviral retrotransposons, the third major type of transposon (see Table 5–4). Although most of these transposons in the human genome are immobile, a few retain the ability to move. Relatively recent movements of the L1 element (sometimes referred to as a LINE or long interspersed nuclear element) have been identified, some of which result in human disease; for example, a particular type of hemophilia results from an L1 insertion into the gene encoding the blood-clotting protein Factor VIII (see Figure 6–24).
binds to L1 RNA
Nonretroviral retrotransposons are found in many organisms and move via a 5˜ distinct mechanism that requires a complex of an endonuclease and a reverse transcriptase. As illustrated in Figure 5–63, the RNA and reverse transcriptase CLEAVAGE OF FIRST STRAND have a much more direct role in the recombination event than they do in the ret- roviral-like retrotransposons described above.
Inspection of the human genome sequence reveals that the bulk of nonretro ber of the SINE (short interspersed nuclear element) family—do not carry their viral retrotransposons—for example, the many copies of the Alu element, a mem-target DNA own endonuclease or reverse transcriptase genes. Nonetheless, they have suc cessfully amplified themselves to become major constituents of our genome, pre- sumably by pirating enzymes encoded by other transposons. Together the LINEs and SINEs make up over 30% of the human genome (see Figure 4–62); there are 500,000 copies of the former and over a million of the latter.
Figure 5–63 Transposition by a nonretroviral retrotransposon.
Transposition of the L1 element (red) begins when an endonuclease attached to the L1 reverse transcriptase (green) and the L1 RNA (blue) nick the target DNA at the point at which insertion will occur. This cleavage releases a 3ʹ-OH DNA end in the target DNA, which is then used as a primer for the reverse transcription step shown. This generates a single-strand DNA copy of the 3˜ element that is directly linked to the target DNA. In subsequent reactions, further processing of the single-strand DNA copy results in the generation of a new double-strand DNA copy of the L1 element that is inserted at the site of the initial nick.
We have described several types of transposable elements: (1) DNA-only transposons, the movement of which is based on DNA breaking and joining reactions; (2) retroviral-like retrotransposons, which also move via DNA breakage and joining, but where RNA has a key role as a template to generate the DNA recombination substrate; and (3) nonretroviral retrotransposons, in which an RNA copy of the element is central to the incorporation of the element into the target DNA, acting as a direct template for a DNA target-primed reverse transcription event.
Intriguingly, different types of transposons predominate in different organisms. For example, the vast majority of bacterial transposons are DNA-only types, with a few related to the nonretroviral retrotransposons also present. In yeasts, the main mobile elements are retroviral-like retrotransposons. In Drosophila, DNA-based, retroviral, and nonretroviral transposons are all found. Finally, the human genome contains all three types of transposon, but as discussed below, their evolutionary histories are strikingly different.
Genome Sequences Reveal the Approximate Times at Which Transposable Elements Have Moved