What are transposons and why are they important?

What are transposons and why are they important? 

Transposons are DNA sequences that move from one place in the genome to another, some on their own and others with help.  These transposable elements (TEs), colloquially known as “jumping genes,” were discovered by geneticist Barbara McClintock. Working with maize at Cold Spring Harbor Laboratory in New York, McClintock identified the Ac/Ds system, which is an example of a class 1 TE or retrotransposon[1]. 

Class 1 TEs produce RNA transcripts and require transcription of the RNA sequences back into DNA (reverse transcription) using reverse transcriptase enzymes before they can move and are often referred to as RNA transposons. There are two types of Class 1 TEs: LTR (long terminal repeat) and non-LTR retrotransposons. Both types can be autonomous or non-autonomous. The latter lack the gene for reverse transcriptase and thus require the presence of another TE that does encode for this protein to be able to jump.  

Class 2 TEs do not require reverse transcription and are referred to as DNA transposons. They can also be autonomous or non-autonomous. The former encode for a transposase, an enzyme that mediates the direct excision of the TE from one location and its insertion into another, making it possible for these transposons to jump on their own.  

Transposons are present in the genomes of nearly all organisms, including humans. In fact, they account for approximately 50% of the human genome[2]. The bulk of TEs in the human genome are retrotransposons, with class 2 TEs making up less than 2%[3]. In addition, both LTR retrotransposons and DNA transposons in the human genome are inactive. Only non-LTRs still actively jump.  

The most common examples of active transposons in the human genome include LINE1 (L1) and Alu. L1 retrotransposons are large (6 kilobases on average) and make up approximately 15%–17% of the human genome[3,4]. Alu retrotransposons are much smaller (a few hundred nucleotides) and are therefore considered to be short interspersed transposable elements (SINEs).  

Most TEs in the human genome have been silenced in one way or another. It is estimated that of all the L1 retrotransposons, only about 100 are active. Some inactive TEs have mutations that inhibit their movement. Others are prevented from jumping because the reverse transcriptase enzyme cannot reach them due to structural changes resulting from chemical modifications, such as DNA methylation. A few have been found to encode for small interfering RNAs (siRNAs) that inhibit transcription from L1[5]. 

Transposons can drive evolution via exon shuffling, which involves movement of not only the TE element, but additional genomic sequences due to imperfect excision[6]. The result is new genetic sequences and genes that increase genetic diversity. 

Controlled gene jumping is also an important component of gene expression systems, where transposons are present in plasmids and can move genes from plasmids to host cell genomes. Use of carefully designed transposon systems such as Lonza’s GS piggyBac® transposon technology can help generate high-performing cell lines and accelerate drug development efforts. 

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  References 

1. Pray, L.  Transposons: The jumping genes. Nature Education 1(1), 204 (2008)  
2. SanMiguel, P., et al. Nested retrotransposons in the intergenic regions of the maize genome. Science 274, 765–768 (1996). 
3. Kazazian, H. H., & Moran, J. V. The impact of L1 retrotransposons on the human genome. Nature Genetics 19, 19–24 (1998) 
4. Slotkin, R. K., & Martienssen, R. Transposable elements and the epigenetic regulation of the genome. Nature Reviews Genetics 8, 272–285 (2007) 
5. Yang, N., & Kazazian, H. H. L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells. Nature Structural and Molecular Biology 13, 763–771 (2006) 
6. Moran, J. V., et al. Exon shuffling by L1 retrotransposition. Science 283, 1530–1534 (1999)