Transposable elements, often referred to as “jumping genes,” are segments of DNA that possess the remarkable ability to change their location within a cell’s genome. The discovery of these mobile genetic elements revolutionized the understanding of genome plasticity and earned Barbara McClintock a Nobel Prize in 1983. These elements are ubiquitous, found across all forms of life, including bacteria, plants, and animals. Their presence can influence the size and structure of a genome, making up a substantial portion of the genetic material in many organisms.
How Transposable Elements Move
Transposable elements employ two primary mechanisms to relocate within a genome: “cut-and-paste” and “copy-and-paste.” The “cut-and-paste” method involves the element excising itself from its original location. This process requires an enzyme called transposase, which recognizes specific sequences at the ends of the transposable element and cleaves the DNA. Once excised, the transposase-bound element then inserts itself into a new target site elsewhere in the genome.
The “copy-and-paste” mechanism creates a new copy of the transposable element. A new copy is made, which then inserts into a new genomic location, leaving the original element intact. This process involves an RNA intermediate, where the DNA element is first transcribed into RNA, then reverse-transcribed back into DNA by reverse transcriptase, before being integrated into the new site. Both mechanisms lead to the duplication of a short sequence of DNA at the new insertion site, known as target site duplications.
Major Types of Transposable Elements
Transposable elements are broadly categorized into two main classes: Class I (Retrotransposons) and Class II (DNA Transposons).
Class I: Retrotransposons
Retrotransposons utilize the “copy-and-paste” method, moving through an RNA intermediate. Their DNA sequence is first transcribed into an RNA molecule, then converted back into a DNA copy by reverse transcriptase, encoded by the retrotransposon itself. This new DNA copy is then inserted into a different genomic location, increasing the number of copies within the genome.
Retrotransposons are common in eukaryotic organisms and make up a large portion of their genomes. Examples include Long Terminal Repeat (LTR) retrotransposons, which resemble retroviruses and encode reverse transcriptase, and non-LTR retrotransposons such as Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs). LINEs encode their own reverse transcriptase, while SINEs do not and rely on other elements for their transposition. Approximately 20% of the human genome is composed of LINEs, demonstrating their widespread presence.
Class II: DNA Transposons
DNA transposons move through the “cut-and-paste” mechanism. These elements excise themselves from one location and reinsert into another without an RNA intermediate. They encode an enzyme called transposase, responsible for both excision and insertion. DNA transposons are found in both prokaryotes and eukaryotes. While less abundant in the human genome compared to retrotransposons, making up about 3.5%, they are considered remnants from ancestral genomes, with no currently active families in humans.
Role in Genome Evolution and Function
Transposable elements contribute to genome evolution by generating genetic variation. Their movement leads to large-scale genomic alterations, including deletions, inversions, and duplications of DNA segments. This constant rearrangement of genetic material provides a source of raw material for evolutionary change and adaptation.
Beyond structural changes, transposable elements also influence gene regulation. When TEs insert near or within genes, they act as enhancers or promoters, altering the expression levels of nearby genes. They also contribute sequences that become part of regulatory RNAs, such as microRNAs and long non-coding RNAs, which play roles in controlling gene activity. This ability to create new regulatory sequences drives evolutionary novelty in gene regulation, often in a tissue-specific manner.
The insertion of transposable elements also leads to the formation of new genes, a process known as molecular domestication, where a TE or part of it becomes a functional gene. For instance, the retrotransposon-derived PEG-10 gene is involved in placental formation. However, the mobility of TEs also has detrimental effects, causing genetic disorders and contributing to diseases like cancer. Their insertion into a gene disrupts its function, leading to insertional mutations, or causes genomic instability through rearrangements like non-allelic homologous recombination. The impact of TE insertions ranges from silent mutations to alternative splicing and altered gene expression, highlighting their complex and multifaceted role in genome function and disease.