Virtually all cells contain mobile genetic elements (known informally as “jumping genes”). As explained in Chapter 4, over evolutionary time scales, they have had a profound effect on the shaping of modern genomes. For example, nearly half of the human genome can be traced to these elements (see Figure 4–62). Over time, random mutation has altered their nucleotide sequences, and, as a result, only a few of the many copies of these elements in our DNA are still active and capable of movement. The remainder are molecular fossils whose existence provides striking clues to our evolutionary history.
Mobile genetic elements are often considered to be molecular parasites (they are also termed “selfish DNA”) that persist because cells cannot get rid of them; they certainly have come close to overrunning our own genome. However, mobile DNA elements can provide benefits to the cell. For example, the genes they carry are sometimes advantageous, as in the case of antibiotic resistance in bacterial cells, discussed below. The movement of mobile genetic elements also produces many of the genetic variants upon which evolution depends, because, in addition to moving themselves, mobile genetic elements occasionally rearrange neighboring sequences of the host genome. Thus, spontaneous mutations observed in Drosophila, humans, and other organisms are often due to the movement of mobile genetic elements. While many of these mutations will be deleterious to the organism, some will be advantageous and may spread throughout the population. It is almost certain that much of the variety of life we see around us originally arose from the movement of mobile genetic elements.
In this section, we introduce mobile genetic elements and describe the mechanisms that enable them to move around a genome. We shall see that some of these elements move through transposition mechanisms and others through conservative site-specific recombination. We begin with transposition, as there are many more known examples of this type of movement.
Through Transposition, Mobile Genetic Elements Can Insert Into Any DNA Sequence
Mobile elements that move by way of transposition are called transposons, or transposable elements. In transposition, a specific enzyme, usually encoded by the transposon itself and typically called a transposase, acts on specific DNA sequences at each end of the transposon, causing it to insert into a new target DNA site. Most transposons are only modestly selective in choosing their target site, and they can therefore insert themselves into many different locations in a genome. In particular, there is no general requirement for sequence similarity between the ends of the element and the target sequence. Most transposons move only rarely. In bacteria, where it is possible to measure the frequency accurately, transposons typically move once every 105 cell divisions. More frequent movement would probably destroy the host cell’s genome.
On the basis of their structure and transposition mechanism, transposons can be grouped into three large classes: DNA-only transposons, retroviral-like retrotransposons, and nonretroviral retrotransposons. The differences among them are briefly outlined in Table 5–4, and each class will be discussed in turn.
DNA-only transposons, so named because they exist only as DNA during their movement, predominate in bacteria, and they are largely responsible for the spread of antibiotic resistance in bacterial strains. When antibiotics like penicillin and streptomycin first became widely available in the 1950s, most bacteria that caused human disease were susceptible to them. Now, the situation is different— antibiotics such as penicillin (and its modern derivatives) are no longer effective against many modern bacterial strains, including those causing gonorrhea and bacterial pneumonia. The spread of antibiotic resistance is due largely to genes that encode antibiotic-inactivating enzymes that are carried on transposons (Figure 5–60). Although these mobile elements can transpose only within cells that already carry them, they can be moved from one cell to another through other mechanisms known collectively as horizontal gene transfer (see Figure 1–19). Once introduced into a new cell, a transposon can insert itself into the genome and be faithfully passed on to all progeny cells through the normal processes of DNA replication and cell division.