TRANSPOSONS FOR MSC LIFESCIENCE STUDENTS

 

Transposons: jumping genes of the genome

Transposons, also known as transposable elements (TEs) or "jumping genes," are segments of DNA that possess the unique ability to move and integrate into new positions within a genome. These mobile genetic elements are ubiquitous across all life forms, ranging from bacteria to humans, and represent a significant portion of many genomes (e.g., 45% of the human genome and up to 90% in some plants). Barbara McClintock's groundbreaking work with maize in the 1940s led to their discovery, revealing that genes are not static but can relocate, influencing genetic instability and driving evolutionary change.

Mechanism of action

Transposons move within a genome via two main mechanisms:

• Cut-and-paste (conservative transposition): In this method, the transposon is excised from its original location and directly inserted into a new site. This mechanism is facilitated by an enzyme called transposase, which recognizes the inverted terminal repeats (IRs) at the ends of the transposon, excises it, and then integrates it into a new target site, often creating target site duplications (TSDs) in the process.
• Copy-and-paste (replicative transposition): This mechanism involves the replication of the transposon, where a copy is made and inserted into the target site while the original copy remains at the donor site. A notable example are the Tn3-elements found in bacteria. Retrotransposons, a class of TEs, utilize an RNA intermediate. The DNA sequence is first transcribed into RNA, which is then reverse-transcribed into a DNA copy by reverse transcriptase before being inserted into a new genomic location

Types of transposons

Transposons are broadly classified into two major classes based on their mechanism of transposition:

• Class I (Retrotransposons): These elements transpose via an RNA intermediate, using reverse transcriptase to convert RNA back into DNA for integration. Examples include Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs), which are prevalent in the human genome.
• Class II (DNA Transposons): These elements move directly as DNA, using a cut-and-paste mechanism catalyzed by transposase. Examples include the Ac/Ds system in maize, P elements in Drosophila, and the Sleeping Beauty (SB) and piggyBac systems used in research.

Significance of transposons

Transposons are now recognized as powerful forces in shaping genomes and contributing to evolutionary processes, despite initially being considered "junk DNA". Their impact extends to various aspects of cell biology and evolution:

Genetic Variation: Transposon insertions and excisions can lead to mutations, affecting gene function and altering gene expression patterns. These changes can impact phenotypes and potentially contribute to adaptation and speciation.

Genome Instability and Disease: Transposon activity can lead to genomic instability through mechanisms such as insertions, deletions, duplications, and chromosomal rearrangements. LINE-1 and Alu insertions are linked to various genetic disorders and cancers in humans.

Genome Evolution: Transposons play a crucial role in the evolution of new genes and functions through mechanisms like gene duplication, exon shuffling, and the creation of novel regulatory elements. Their activity can also contribute to the formation of heterochromatin and the regulation of gene regulatory networks.

Gene Regulation: Transposons can influence gene expression through various mechanisms, including:Epigenetic Modifications: They can attract machinery responsible for heterochromatin formation and DNA methylation, leading to gene silencing or affecting gene expression of nearby genes.

Cis-regulatory elements: They can provide binding sites for transcription factors, influencing gene expression.

Tools for Genetic Engineering: Transposon systems like Sleeping Beauty and piggyBac have been engineered and are widely used in research for insertional mutagenesis, gene therapy, creating transgenic organisms, and functional genomics studies.

Transposons in disease

Transposon insertions and excisions can be pathogenic, leading to alterations in gene expression and disrupting normal cellular functions. Examples include Kindler syndrome (FERMT1 gene) and hemophilia A (Factor VIII gene). Transposon inserts may also influence susceptibility to multifactorial diseases like tumors by creating hypomorphic alleles (alleles with reduced function).