Within an organism’s genome are dynamic segments of DNA known as transposable elements (TEs), often called “jumping genes.” These sequences can move from one location to another, meaning a TE is not fixed in place like most genes and can rearrange the genetic blueprint.
These mobile elements are found in the genomes of nearly all organisms, from bacteria to complex plants and animals. TEs and their remnants constitute a significant portion of many genomes; in humans, they make up nearly half of our DNA.
By inserting into new locations, TEs can alter the genetic landscape by creating new instructions or disrupting existing ones. This mobility introduces a layer of fluidity to the otherwise stable structure of a chromosome. Their existence reveals that the genome is not a static script but a dynamic environment subject to internal change and reorganization.
The Discovery of Jumping Genes
The concept of mobile genes was uncovered by Barbara McClintock in the 1940s and 1950s. While studying maize (corn), she observed unexpected patterns of coloration in the kernels. Instead of following predictable inheritance patterns, some kernels displayed a mosaic of colors, which McClintock deduced was the result of genetic elements physically moving within the chromosomes.
Her research demonstrated that these mobile units, which she named “controlling elements,” could insert themselves into or near other genes, affecting their function. For instance, when a TE jumped into a gene for purple kernel color, it could disrupt the gene’s activity, resulting in a colorless kernel. If that same TE later jumped out, the gene’s function could be restored, causing colored spots to appear on the colorless background.
At the time, the prevailing scientific view held that genes were fixed entities, arranged in a stable, linear order on chromosomes. McClintock’s idea that genes could be mobile was met with skepticism from the scientific community, and her work was largely overlooked for decades. It wasn’t until the 1970s, when similar mobile elements were discovered in other organisms, that her discovery was recognized, leading to her being awarded the Nobel Prize in Physiology or Medicine in 1983.
Mechanisms and Classifications of Transposition
Transposable elements are categorized into two main classes based on their method of movement. These strategies are often analogized as “cut-and-paste” and “copy-and-paste” mechanisms.
Class II elements, known as DNA transposons, operate via a “cut-and-paste” pathway. These elements produce an enzyme called transposase, which recognizes and binds to specific sequences at the ends of the transposon. The enzyme then cuts the TE out of its original location in the DNA and moves it to a new target site, where it is integrated into the chromosome. This process is a direct relocation, as the element is excised and inserted elsewhere without creating a new copy.
In contrast, Class I elements, or retrotransposons, use a “copy-and-paste” mechanism that involves an RNA intermediate. The process begins when the retrotransposon’s DNA is transcribed into an RNA molecule. This RNA molecule then serves as a template for an enzyme called reverse transcriptase, which synthesizes a new DNA copy of the element. This newly made DNA copy is then inserted into a different location in the genome, while the original retrotransposon remains at its starting position.
This “copy-and-paste” method means that retrotransposons can accumulate rapidly, leading to a significant increase in their numbers within the genome. This class includes Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs). LINEs encode the proteins needed for their own replication, though many SINEs are “non-autonomous” and rely on the machinery of LINEs to move.
Impact on Genome Evolution
The activity of transposable elements has shaped the structure and function of genomes over evolutionary time. By moving to new locations, TEs serve as a source of genetic variation. An insertion can directly disrupt the coding sequence of a gene or land in a regulatory region, altering how a gene is turned on or off, which can lead to new traits.
TEs also contribute to large-scale genome restructuring. The presence of numerous copies of the same TE scattered throughout the genome can facilitate a process called non-allelic homologous recombination. This can lead to chromosomal rearrangements, such as deletions, duplications, and inversions of large DNA segments. TEs can also occasionally capture and move fragments of host genes, a phenomenon known as exon shuffling, which can lead to the creation of novel genes.
The accumulation of retrotransposons is a primary reason for the vast differences in genome size observed across different species. In humans, the vast majority of TEs are no longer active and exist as “molecular fossils.” These are remnants of past transposition events that have become permanent fixtures in our DNA.
Relevance to Human Health
Although most transposable elements in the human genome are inactive, a small number remain capable of moving, and their activity can have direct consequences for human health. When a TE inserts into a gene, it can disrupt its ability to produce its corresponding protein, leading to genetic disorders. This mechanism has been identified as the cause of certain inherited diseases.
For instance, new insertions of an L1 retrotransposon into the Factor VIII gene, which is necessary for normal blood clotting, can cause some cases of hemophilia A. Similarly, TE insertions can disrupt the dystrophin gene, leading to Duchenne muscular dystrophy. The insertion effectively breaks the gene’s instructions, preventing the production of a functional protein.
Beyond single-gene disorders, TE activity has been implicated in more complex diseases. In many types of cancer, the cellular mechanisms that normally suppress TE activity are compromised, leading to increased transposition. This can contribute to genomic instability by activating cancer-promoting genes or inactivating tumor-suppressor genes. Research is also exploring the role of reactivated TEs in the aging process and in the development of neurodegenerative diseases.