Within every living organism’s genetic blueprint are segments of DNA that can relocate. These sequences are known as mobile genes or transposable elements (TEs). First identified in the 1940s, these genetic materials can change their position within a genome, the complete set of genetic instructions, which has led to them being nicknamed “jumping genes.” Mobile genes are a significant component of the genomes of almost all organisms, and in humans, they constitute nearly half of our entire genome. Their movement provides a continual source of genetic variation, shaping the structure and function of the genome over time.
The Mechanism of Genetic Movement
The movement of mobile genes, a process called transposition, is managed by two primary mechanisms. The first is a “cut-and-paste” pathway used by a group known as DNA transposons. This process begins when an enzyme called transposase, often encoded by the transposon itself, recognizes and binds to the ends of the mobile element. This enzyme then excises the transposon from its original location in the chromosome.
After being cut out, the transposon-enzyme complex moves to a new target site in the genome. The transposase then facilitates the insertion of the mobile DNA into this new position. This mechanism is direct, moving the DNA sequence from one spot to another without making a copy. The process is analogous to cutting a sentence from one paragraph in a document and pasting it into another.
The second major mechanism is described as “copy-and-paste” and is characteristic of retrotransposons. Unlike the direct DNA-to-DNA movement, this pathway involves an RNA intermediate. First, the retrotransposon’s DNA is transcribed into an RNA molecule. This RNA copy then serves as a template for an enzyme called reverse transcriptase, which synthesizes a new DNA copy of the element.
This newly created DNA copy is then integrated into a different location in the genome, while the original retrotransposon remains in its initial position. This results in an increase in the number of copies of the mobile element within the genome. This method is similar to copying text in a document and pasting the duplicate elsewhere, leaving the original text untouched.
Genomic Impact of Mobile Genes
When a mobile gene moves to a new location, it can have significant consequences for the genome’s function. One of the most direct effects is insertional mutagenesis. If a transposable element inserts itself into the middle of a functional gene, it can disrupt the gene’s sequence, often preventing the production of a functional protein.
A TE insertion can also change how genes are regulated. If a mobile element lands in a regulatory region near a gene, it can alter the gene’s expression levels. This can lead to the gene being turned on or off at inappropriate times or in the wrong tissues.
These movements are not always disruptive. The insertion of mobile elements can also be a source of genetic novelty. The shuffling of genetic material can lead to the creation of new genes or new regulatory networks. By rearranging existing gene segments, TEs can contribute to the evolution of new functions and traits.
Role in Evolution and Human Health
This ongoing genetic activity has direct implications for human health. While many mobile elements are inactive, some can still move, and their transposition can cause disease. Insertional mutagenesis by a TE is the cause of certain genetic disorders. For example, insertions into the factor VIII gene can disrupt its function and lead to some cases of hemophilia A.
Beyond inherited disorders, mobile element activity is also observed in the context of cancer. In some tumors, the cellular machinery that normally keeps TEs in check is disrupted, leading to new insertions. These somatic, or non-inherited, insertions can inactivate tumor suppressor genes or activate oncogenes, contributing to the development and progression of the cancer.
The Discovery and Study of Mobile Genes
The existence of mobile genes was first uncovered through the work of Barbara McClintock in the 1940s. While studying maize (corn), she observed patterns of coloration in kernels that could not be explained by standard genetics. McClintock hypothesized that “controlling elements” were moving within the maize genome, causing these visible changes in traits. Her findings, demonstrating that genes were not fixed in position, were a radical departure from the scientific consensus of the time.
Initially, McClintock’s work was met with skepticism from the broader scientific community. It wasn’t until the late 1960s and 1970s, with the discovery of similar elements in bacteria and the mechanisms of retroviruses, that the importance of her findings was widely recognized. For her pioneering discovery of transposable elements, Barbara McClintock was awarded the Nobel Prize in Physiology or Medicine in 1983.
Today, scientists have harnessed the power of these mobile elements, turning them into valuable tools for genetic research. Researchers can use transposons to create insertion mutations deliberately, allowing them to study the function of specific genes by observing the effects of their disruption.