Retrotransposons are segments of genetic material often referred to as “jumping genes” because of their ability to move and multiply within an organism’s DNA. These mobile genetic elements are abundant, making up a substantial portion of many eukaryotic genomes, including approximately 42% to nearly 50% of the human genome. Their widespread presence suggests a dynamic role in the genetic landscape.
How Retrotransposons Replicate and Integrate
Retrotransposons operate using a “copy-and-paste” mechanism, distinct from other mobile genetic elements that “cut and paste.” This process begins when the retrotransposon’s DNA sequence is first transcribed into an RNA molecule. This RNA then serves as a template for a specialized enzyme called reverse transcriptase.
Reverse transcriptase takes the RNA template and synthesizes a new DNA copy from it, a process known as reverse transcription. This newly created DNA copy, or cDNA, is then integrated into a new location within the host genome. This mechanism ensures that the original retrotransposon copy remains at its initial site, while a new copy is added elsewhere, leading to an increase in their overall number within the genome.
The integration process can vary depending on the type of retrotransposon. For instance, non-LTR (Long Terminal Repeat) retrotransposons, which are prevalent in humans, utilize a process called target-primed reverse transcription (TPRT). This involves the retrotransposon’s RNA being reverse transcribed and inserted at a specific site. In contrast, LTR retrotransposons, more common in plants, undergo reverse transcription in the cytoplasm before insertion.
Retrotransposons’ Impact on Genome Evolution
Retrotransposons influence genome evolution over time. Their “copy-and-paste” method allows them to rapidly amplify their numbers, significantly increasing the overall size and content of genomes. For example, their presence accounts for significant variation in the maize genome.
The insertion of retrotransposons can directly affect gene regulation. If an insertion occurs near or within a gene, it can alter the gene’s expression patterns, sometimes acting as new regulatory elements like promoters or enhancers. This can lead to changes in phenotypes, such as the kernel color variations observed in maize due to transposable element activity.
Beyond gene regulation, retrotransposons contribute to genomic rearrangements, including deletions, duplications, and inversions, by facilitating non-allelic homologous recombination. This activity can also lead to the duplication of entire genes, providing raw material for the evolution of new gene functions and traits, a process known as neofunctionalization. For instance, a specific group of retrotransposons is linked to the triplication of the AMAC gene in the human genome.
Retrotransposons and Human Health
While many retrotransposons in the human genome are now inactive due to mutations or cellular silencing mechanisms, a small subset can still move and insert new copies. This ongoing activity can have consequences for human health. Aberrant retrotransposon activity can lead to genetic disorders by disrupting gene function.
Insertions of retrotransposons can cause disease by landing within a gene, thereby interfering with its normal operation. For example, an insertion of a LINE-1 retrotransposon into the RPS6KA3 gene is associated with Coffin-Lowry syndrome, a condition characterized by intellectual disability and physical abnormalities. Similarly, an Alu retrotransposon insertion into the BRCA1 gene is recognized as a risk factor for hereditary cancer.
Retrotransposon activity has also been implicated in more complex diseases. While direct causal links are still being explored, their dysregulation or new insertions have been associated with certain cancers, such as colon cancer, and some neurological conditions like schizophrenia. Overall, approximately 0.27% of all known human disease mutations are attributed to retrotransposable elements, highlighting their occasional, yet significant, impact on genetic health.