The nucleotide sequence of the human genome provides a rich fossil record of the activity of transposons over evolutionary time spans. By carefully comparing the nucleotide sequences of the approximately 3 million transposable element remnants in the human genome, it has been possible to broadly reconstruct the movements of transposons in our ancestors’ genomes over the past several hundred million years. For example, the DNA-only transposons appear to have been very active well before the divergence of humans and Old World monkeys (25–35 million years ago), but because they gradually accumulated inactivating mutations, they have been dormant in the human lineage since that time. Likewise, although our genome is littered with relics of retroviral-like retrotransposons, none appear to be active today. Only a single family of retroviral-like retrotransposons is believed to have transposed in the human genome since the divergence of human and chimpanzee approximately 6 million years ago. The nonretroviral retrotransposons are also ancient, but in contrast to other types, some are still moving in our genome, as mentioned previously. For example, it is estimated that de novo movement of an Alu element is seen once in every 100–200 human births. The movement of nonretroviral retrotransposons is responsible for a small but significant fraction of new human mutations—perhaps two mutations out of every thousand.
The situation in mice is significantly different. Although the mouse and human genomes contain roughly the same density of the three types of transposons, both types of retrotransposons are still actively transposing in the mouse genome, being responsible for approximately 10% of new mutations.
Although we are only beginning to understand how the movements of transposons have shaped the genomes of present-day mammals, it has been proposed that bursts in transposition activity could have been responsible for critical speciation events during the radiation of the mammalian lineages from a common ancestor, a process that began approximately 170 million years ago. At present, we can only wonder how many of our uniquely human qualities arose from the past activity of the many mobile genetic elements whose remnants are found today scattered throughout our chromosomes.
A different kind of recombination mechanism, known as conservative site-specific recombination, rearranges other types of mobile DNA elements. In this pathway, breakage and joining occur at two special sites, one on each participating DNA
Figure 5–64 Two types of DNA rearrangement produced by conservative site-specific recombination. The only difference between the reactions in (A) and (B) is the relative orientation of the two short DNA sites (indicated by arrows) at which a site-specific recombination event occurs.
Through an integration reaction, a circular DNA molecule can become incorporated into a second DNA molecule; by the reverse reaction (excision), it can exit to re-form the original DNA circle. Many bacterial viruses move in and out of their host chromosomes in this way.
Conservative site-specific recombination can also invert a specific segment of DNA in a chromosome. A well-studied example of DNA inversion through site-specific recombination occurs in the bacterium Salmonella typhimurium, an organism that is a major cause of food poisoning in humans; as described in the following section, the inversion of a DNA segment changes the type of flagellum that is produced by the bacterium.
molecule. Depending on the positions and relative orientations of the two recombination sites, DNA integration, DNA excision, or DNA inversion can occur (Figure 5–64). Conservative site-specific recombination is carried out by specialized enzymes that break and rejoin two DNA double helices at specific sequences on each DNA molecule. The same enzyme system that joins two DNA molecules can often take them apart again, precisely restoring the sequence of the two original DNA molecules (see Figure 5–64A).