Jumping genes

Jumping genes, scientifically known as transposable elements (TEs) or transposons, are segments of DNA that can move or “jump” from one location to another within a genome. Their discovery revolutionised genetics by revealing that the genome is not a static collection of genes but a dynamic and evolving system. Jumping genes play vital roles in genome organisation, evolution, gene regulation, and even in causing certain mutations and diseases.
The term “jumping gene” was first introduced following the pioneering work of Barbara McClintock in maize (corn), who discovered mobile genetic elements in the 1940s — a finding that earned her the Nobel Prize in Physiology or Medicine in 1983.

Discovery and Historical Background

In the early twentieth century, geneticists believed that genes occupied fixed positions on chromosomes. However, Barbara McClintock challenged this view through her studies on the colour variations in maize kernels.
While examining chromosome behaviour, McClintock observed that certain DNA segments could change position, influencing the expression of neighbouring genes and altering kernel pigmentation. She termed these elements “controlling elements.”
Her discoveries went largely unrecognised until molecular genetics in the 1960s and 1970s confirmed that similar mobile DNA sequences exist in bacteria, animals, and humans — thus establishing the universal presence of transposable elements.

Definition and Basic Concept

A transposable element is a DNA sequence that can move or copy itself from one genomic location to another. The process of movement is called transposition, and it can occur within a chromosome, between chromosomes, or even between genomes (in bacteria).
Transposons can move either by a “cut-and-paste” or a “copy-and-paste” mechanism, depending on the type of element involved.

Types of Transposable Elements

Transposable elements are broadly classified into two major classes based on their mechanism of movement:

1. Class I – Retrotransposons (Copy and Paste Mechanism)

• Move through an RNA intermediate.
• First transcribed from DNA to RNA, then reverse-transcribed back into DNA by the enzyme reverse transcriptase and inserted into a new genomic site.
• The original copy remains in place, increasing the total number of copies.

Subtypes:

• LINEs (Long Interspersed Nuclear Elements): Autonomous elements that encode reverse transcriptase. Example: LINE-1 (L1) in humans.
• SINEs (Short Interspersed Nuclear Elements): Non-autonomous elements that depend on LINEs for transposition. Example: Alu elements in humans.
• LTR Retrotransposons: Contain long terminal repeats similar to retroviruses. Example: Ty elements in yeast.

Example: In humans, retrotransposons make up about 40% of the genome.

2. Class II – DNA Transposons (Cut and Paste Mechanism)

• Move directly as DNA using the enzyme transposase, which recognises terminal inverted repeats (TIRs) at the ends of the element.
• The element is excised from one location and inserted into another, often leaving a short duplication of target DNA.

Examples:

• Ac/Ds elements discovered by Barbara McClintock in maize.
• P elements in Drosophila melanogaster (fruit fly).
• Sleeping Beauty transposon system used in genetic engineering.

Mechanism of Transposition

Transposition involves several key steps depending on the type of transposon:

1. Recognition: Transposase or reverse transcriptase enzymes identify specific sequences at the ends of the transposon.
2. Excision or Copying:
   • DNA transposons are excised from the original site.
   • Retrotransposons are transcribed into RNA and reverse-transcribed into complementary DNA (cDNA).
3. Insertion: The transposon (or its copy) is inserted at a new site in the genome, often creating target site duplications (TSDs) due to staggered cuts in the DNA.

This process can disrupt existing genes, activate dormant ones, or cause chromosomal rearrangements, contributing to genetic diversity and sometimes genomic instability.

Functions and Significance

Transposable elements, though once regarded as “junk DNA,” are now recognised as major drivers of genome evolution and function.
1. Genetic Variation and Evolution:

• Transposons introduce mutations by inserting into genes or regulatory regions.
• They contribute to genomic rearrangements, such as duplications, inversions, and deletions.
• Over evolutionary time, they help in the formation of new genes and regulatory networks.

2. Gene Regulation:

• Transposon-derived sequences can act as enhancers, silencers, or promoters, influencing gene expression.
• Their mobilisation can activate or deactivate genes in response to environmental stress.

3. Genome Size Expansion:

• The accumulation of transposons significantly increases genome size.
• For example, in humans, over 45% of the genome consists of transposable elements or their remnants.

4. Defence and Immunity:

• Some elements contribute to immune system diversity; for instance, V(D)J recombination in antibody formation shares mechanisms similar to transposon activity.

5. Biotechnology and Genetic Engineering:

• Transposons serve as tools for gene tagging, mutagenesis, and gene transfer in research.
• Artificial transposon systems, such as Sleeping Beauty, are used in gene therapy and cancer research to insert therapeutic genes into host genomes.

Examples in Different Organisms

• Maize (Zea mays): Ac/Ds elements discovered by McClintock cause colour variation in kernels.
• Fruit Fly (Drosophila): P elements are responsible for hybrid dysgenesis and are used in genetic manipulation.
• Bacteria: Insertion sequences and composite transposons carry antibiotic resistance genes (e.g., Tn3, Tn10).
• Humans: Alu and LINE-1 elements are abundant and still occasionally active, contributing to genetic disorders.

Impact on Human Health

While transposons have evolutionary benefits, their activity can sometimes lead to disease:

• Insertional Mutations: Integration within a gene can disrupt its function, leading to disorders like haemophilia or Duchenne muscular dystrophy.
• Chromosomal Rearrangements: Transposon-mediated recombination can cause deletions or translocations linked to cancers.
• Aging and Neurological Diseases: Reactivation of transposable elements has been implicated in age-related genome instability and neurodegenerative diseases such as Alzheimer’s.

Cells counteract transposon activity through epigenetic mechanisms like DNA methylation and RNA interference (RNAi) to maintain genomic stability.

Transposable Elements and Evolutionary Perspective

Transposons are now understood as powerful agents of genomic innovation:

• They facilitate horizontal gene transfer between species in bacteria.
• In vertebrates, transposon-derived sequences have evolved into functional genes and regulatory elements.
• Many essential genomic features, including telomerase components and placental development genes, trace their origins to ancient transposon insertions.

Thus, transposable elements are not mere parasites of the genome but key players in genomic adaptation and complexity.