What are transposons and how do they cause mutations?

What are Transposons?

Transposons are segments of DNA capable of moving from one location to another within the genome. They are ubiquitous in both prokaryotic and eukaryotic organisms. Their movement doesn’t necessarily involve replication; they can ‘jump’ directly or use a ‘copy-and-paste’ mechanism. Transposons are generally flanked by short, direct repeats, which are generated during the transposition process.

Classification of Transposons

Transposons are broadly classified into two main classes:

• Class I Transposons: Retrotransposons – These transposons move via an RNA intermediate. They are transcribed into RNA, then reverse transcribed back into DNA by reverse transcriptase (an enzyme encoded by the transposon itself), and finally inserted into a new genomic location. They leave a ‘copy’ of themselves at the original site. There are several subclasses:
  • Long Terminal Repeat (LTR) retrotransposons: Resemble retroviruses, possessing long terminal repeats at both ends.
  • Non-LTR retrotransposons: Lack LTRs and include LINEs (Long Interspersed Nuclear Elements) and SINEs (Short Interspersed Nuclear Elements). LINEs encode reverse transcriptase, while SINEs rely on the reverse transcriptase of LINEs for their mobilization.
• Class II Transposons: DNA Transposons – These transposons move directly as DNA, without an RNA intermediate. They utilize a ‘cut-and-paste’ mechanism, excising themselves from one location and inserting into another. They are further categorized into:
  • Insertion Sequences (IS elements): Contain genes encoding only the transposase enzyme, necessary for their movement.
  • Composite Transposons: Contain genes for transposase and often additional genes, flanked by IS elements.

Mechanisms of Mutation by Transposons

Transposons can induce mutations through several mechanisms:

1. Insertion Mutagenesis

The most direct mechanism is insertion mutagenesis. When a transposon inserts itself into a gene, it can disrupt the gene’s coding sequence, leading to a loss-of-function mutation. The severity of the mutation depends on where the transposon inserts within the gene. Insertions within regulatory regions can also alter gene expression.

2. Ectopic Recombination

Transposons present at multiple locations in the genome can mediate ectopic recombination (unequal crossing over). This occurs when homologous sequences within different transposons align during meiosis, leading to deletions, duplications, or inversions of the DNA between them. This can disrupt genes or alter gene dosage.

3. Chromosome Rearrangements

Transposons can contribute to larger-scale chromosome rearrangements, such as deletions, inversions, and translocations. This is particularly common with composite transposons, where the flanking IS elements can facilitate recombination events.

4. Alteration of Gene Expression

Even if a transposon doesn’t directly disrupt a gene’s coding sequence, its insertion near a gene can alter its expression. Transposons often contain promoters and enhancers that can influence the transcription of nearby genes, leading to either increased or decreased gene expression.

Examples of Transposon-Induced Mutations

• Human Diseases: Insertions of retrotransposons have been linked to several human diseases, including hemophilia A (caused by insertion of a LINE-1 element into the F8 gene) and some forms of cancer.
• Antibiotic Resistance in Bacteria: Transposons play a crucial role in the spread of antibiotic resistance genes among bacteria. Resistance genes are often carried on transposons, allowing them to jump between plasmids and chromosomes.
• Kernel Color in Maize: McClintock’s original discovery involved the effect of a transposon (Ac/Ds system) on kernel color in maize. The insertion of a Ds element into a gene controlling pigment production resulted in variegated kernel coloration.

The activity of transposons is often regulated by epigenetic mechanisms, such as DNA methylation and histone modification. However, these regulatory mechanisms can be compromised, leading to increased transposon activity and genomic instability.