Transposable elements (TEs), often called “jumping genes,” are segments of DNA that change their position within an organism’s genome. This movement, known as transposition, was first discovered in maize by scientist Barbara McClintock in the 1940s, a finding that revolutionized genetics. These mobile sequences are distinct from stable genes because they do not have a fixed location and can insert themselves into new genomic sites. The presence and movement of TEs can impact the surrounding DNA, making them a source of genetic change.
The Two Major Classes of Transposable Elements
Transposable elements are classified into two fundamental categories based on the molecular intermediate used for movement. The first major group is Class I, known as retrotransposons, which utilize an RNA molecule as an intermediate.
Retrotransposons operate using a “copy-and-paste” mechanism: the original element remains in place while a new copy is inserted elsewhere in the genome. This strategy allows them to proliferate and increase their copy number within the host genome. Common examples in humans include Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs), with LINEs making up about 20% of the human genome.
The second major group is Class II, referred to as DNA transposons, which move directly as a DNA segment. These elements employ a “cut-and-paste” method, excising themselves from their original location before inserting into a new site. Unlike retrotransposons, this mechanism typically relocates the element without increasing its total number.
DNA transposons encode a specific enzyme called transposase, which is necessary for their excision and re-integration. While they are less abundant in the human genome (about 3%), they are prominent in other organisms.
How Transposable Elements Move
The mechanics of transposition differ between the two classes, relying on distinct enzymes and intermediate molecules. Class I retrotransposons begin movement by being transcribed from DNA into an RNA molecule, which serves as the template for a new DNA copy.
The RNA is converted back into complementary DNA (cDNA) through the action of reverse transcriptase. This reverse transcriptase is often encoded by the retrotransposon itself. Following cDNA creation, an integrase or endonuclease facilitates the insertion of this new DNA copy into a new location in the host genome.
Class II DNA transposons rely on the encoded transposase enzyme to orchestrate movement. The transposase recognizes specific DNA sequences, known as inverted repeats, found at both ends of the element. The enzyme simultaneously cuts the transposon out of its original site and creates a staggered break at the target insertion site.
The transposon is subsequently ligated into the target site. Gaps resulting from the staggered cut are filled by the host cell’s DNA repair machinery. This repair process results in a short duplication of the target sequence flanking the newly inserted transposon, which is a molecular hallmark of DNA transposition.
Transposable Elements and Genome Size
Transposable elements contribute significantly to the overall size and structure of eukaryotic genomes. In humans, TEs and their remnants collectively account for 44% to 50% of the entire genome sequence. This high proportion results directly from the “copy-and-paste” mechanism used by retrotransposons.
The replication of retrotransposons like LINEs and SINEs has driven genome expansion over evolutionary time. For instance, LINE-1 and Alu elements account for approximately 30% of the human genome. While many elements have become inactive, their abundance distinguishes the genome size of different species.
The large volume of mobile DNA led to TEs being labeled as “junk DNA” or “selfish DNA” because their primary function appeared to be self-propagation. This term is misleading, as evidence shows that sequences derived from TEs have been co-opted to play regulatory roles. The proliferation of these repetitive sequences is a major factor in the large size of many eukaryotic genomes, such as maize, where TEs can constitute up to 90% of the genome.
The Role of Transposable Elements in Evolution and Disease
The movement of transposable elements drives both evolutionary change and genetic disease. TEs are recognized as agents of genetic diversity and adaptation. Their insertion near or within genes can alter gene expression patterns by creating new regulatory sequences, such as promoters or enhancers.
TEs can facilitate the shuffling of genetic material, leading to the creation of novel genes or changes in gene structure, a process called “molecular domestication.” Multiple copies of the same element provide sites for unequal crossing over and recombination, resulting in chromosomal rearrangements like deletions or duplications that drive speciation. This contribution allows organisms to adapt more rapidly to environmental challenges.
The negative side of TE activity is their potential to cause disease through insertional mutagenesis. This occurs when an active TE inserts itself directly into a functional gene or its regulatory region, disrupting normal control. Such insertions can lead to genetic disorders like hemophilia, neurofibromatosis, and certain types of cancer. The active L-1 retrotransposon is a potent insertional mutagen frequently linked to sporadic genetic disorders. Their repetitive nature can also predispose the genome to structural variations and rearrangements.