In their study, Lewis et al used what is known as a “mobile genetic element” or transposons to generate mutations. A transposon is a piece of DNA that can move (jump) from place to place in the genome259. The geneticist (and Nobel prize winner) Barbara McClintock (1902–1992) first identified transposons in the course of studies of maize (Zea mays)260. There are two basic types of transposons. Type II transposons consist of a DNA sequence that encodes proteins that enable it to excise itself from a larger (host) DNA molecule, and insert into another site within the host cell’s genome - it jumps from place to place in the genome. The second, type I, transposon can make copies of themselves, through an RNA intermediate, and this copy can be used to generate a complementary DNA that can then be inserted into the host genome, leaving the original copy in place. Both types of transposon encode the proteins required to recognize the transposon sequence and mediated its movement or replication, and subsequent inserting into new sites. If the transposon sequence is inserted into a gene, it can create a null or amorphic mutation in that gene by disrupting the gene’s regulatory or coding sequences. Transposons are only one of a class of DNA molecules that can act as molecular parasites, something neither Darwin nor the founders of genetics anticipated, but which makes sense from a molecular perspective, once the ability to replicate, cut, and join DNA molecules had evolved. These various activities are associated with the repair of mutations involving single and double stranded breaks in DNA, but apparently they also made DNA-based parasites possible. If a host cell infected with a transposon replicates, it also replicates the transposon sequence, which will be inherited by the offspring of the cell. This is a process known as vertical transmission, a topic we will return to shortly.
Because transposons do not normally encode essential functions, mutations can inhibit the various molecular components involved in their replication and jumping within a genome. They can be inactivated (killed) by random mutation, and there is no (immediate or apparent) selective advantage to maintaining them. If you remember back to our discussion of DNA, the human and many other types of genomes contain multiple copies of specific sequences. Subsequent analyses have revealed that these represent “dead” forms of transposons and related DNA-based molecular parasites. It is estimated that the human genome contains ~50,000 copies of the Alu type transposon and that ~50% of the human genome consists of dead transposons. It is probably not too surprising then that there is movement within genomes during the course of an organism’s life time, since some transposons are still active.