Transposable elements, or "jumping genes," are DNA sequences that move within genomes. They contain genes for their own movement and are flanked by repeats. These elements can disrupt genes, alter expression, or cause genome rearrangements when they insert into new locations.

There are two main types: DNA transposons and retrotransposons. DNA transposons use a "cut-and-paste" mechanism, while retrotransposons use "copy-and-paste" via RNA. These elements impact evolution, contribute to genetic variation, and can cause diseases like hemophilia and certain cancers.

Transposable Elements

Structure and function of transposable elements

• Transposable elements (TEs) are DNA sequences that can move from one location to another within a genome also known as "jumping genes" or transposons
• TEs contain genes necessary for their own transposition including enzymes such as transposase or reverse transcriptase
• TEs are flanked by inverted repeats or long terminal repeats (LTRs) which are important for the transposition process
• TEs can insert themselves into various locations in the genome and these insertions can disrupt genes, alter gene expression, or cause genome rearrangements (deletions, duplications, inversions)

DNA transposons vs retrotransposons

• DNA transposons move directly as DNA sequences from one location to another and encode a transposase enzyme that facilitates the "cut-and-paste" mechanism (Ac/Ds elements in maize, P elements in Drosophila)
• Retrotransposons transpose via an RNA intermediate and encode a reverse transcriptase enzyme that converts the RNA back into DNA using a "copy-and-paste" mechanism, increasing in number with each transposition event
  • LTR retrotransposons have long terminal repeats at their ends
  • Non-LTR retrotransposons lack LTRs and include LINE-1 elements in humans

Mechanisms and effects of transposition

• DNA transposon transposition mechanism:
  1. Transposase recognizes and binds to the inverted repeats
  2. Transposase excises the transposon from its original location
  3. The excised transposon is inserted into a new target site
• Retrotransposon transposition mechanism:
  1. Retrotransposon is transcribed into RNA
  2. Reverse transcriptase converts the RNA back into DNA
  3. The new DNA copy is inserted into a new target site
• Effects on gene expression: TE insertions can disrupt coding sequences or regulatory regions, alter splicing patterns or introduce premature stop codons, and provide alternative promoters or enhancers, modulating gene expression
• Effects on genome stability: TE insertions can cause chromosomal rearrangements, and recombination between TEs at different locations can lead to genome instability

Evolutionary impact of transposable elements

• TEs are a major component of many eukaryotic genomes, making up nearly 50% of the human genome
• TEs contribute to genome size and complexity through genome expansion and their sequences can be co-opted for regulatory functions or new genes
• TEs are a source of genetic variation as insertions, deletions, and rearrangements can lead to novel phenotypes and play a role in adaptation and evolution
• TEs can influence gene expression and function by providing alternative promoters, enhancers, or splicing sites and contributing to the evolution of gene regulation networks

Transposable elements in disease

• Hemophilia A is caused by insertions of L1 retrotransposons into the Factor VIII gene, disrupting the coding sequence and leading to a deficiency in blood clotting
• Duchenne muscular dystrophy can be caused by deletions in the dystrophin gene due to recombination between Alu elements, leading to loss of functional dystrophin protein and progressive muscle weakness
• In cancer, TE insertions can activate oncogenes or disrupt tumor suppressor genes, and L1 retrotransposition has been observed in various types of cancer, contributing to genomic instability which is a hallmark of cancer cells