Cyagen Biosciences Newsletter

Transposons, and why you should love them.

The vast majority of biomedical and genetics research is focused on the function of proteins and proteins-coding genes. However, only a few percent of the human genome’s three billion base pairs encodes proteins. In contrast, transposable elements (TEs) comprise greater than half of the human and mouse genomes. It has been suggested that the human genome contains 3-4 million individual TE integrants, which means that they outnumber protein-coding genes by 100-fold.

TEs are poorly understood and essentially ignored by many researchers, yet they represent an important aspect of biology, and have the potential to be powerful research and therapeutic tools. Where did these mysterious DNA elements come from? Why are they so abundant in our genomes? How are TEs regulated? And, what can they do?

Where? – Most TEs within animal genomes are believed to have derived from viruses which integrated into the germ line, thereby becoming heritable within an organism in a Mendelian fashion, and somewhere along the way, lost their ability to spread to other cells. So, TEs can quite accurately be thought of as viruses without an extracellular phase which live within a genome. Like viruses, TE sequences contain genes, or at least the remnants of genes, and transcription of TE sequences can facilitate mobilization of a TE within the cellular genome.

Why? – Although TEs can have deleterious effects, in higher animals they have become essential contributors to evolution, and have been described as the “motors of evolution”. By carrying out processes such as gene rearrangement, mutation of gene and regulatory sequences, genomic recombination, gene duplication, and other types of rearrangements, TEs have provided the adaptive benefit of increased genetic diversity and plasticity for their host species. TEs and their hosts have been forced to coevolve, and have achieved a fine balance between the potentially damaging and potentially beneficial effects of TEs.

How? – In order to prevent TEs from causing unacceptable damage to the genome, host organisms and TEs have evolved ways to control TE mobilization and expression of TE genes. In many cases, TEs have evolved to an inactive state, and simply exist in the genome as nonfunctional DNA sequence. In other cases, TEs are actively repressed by cellular mechanisms such as epigenetic control via histone modification and DNA methylation, as well as by sequence-specific recognition by protein- and RNA-based repressors.

What? – Because of their relatively simple design and inherent ability to move DNA sequences TEs can be very useful molecular tools. For many years, TEs have been used by researchers as tools for mutagenesis, particularly by geneticists and molecular biologists working with Drosophila and plants. More recently, experimentally and therapeutically useful TE systems for use in mammalian systems have been described. One of the primary examples is the PiggyBac transposon. When activated, PiggyBac can transpose in a variety of organisms, and shows precise excision without leaving behind genomic mutations. 

Cyagen Biosciences provides custom mouse and rat models, including PiggyBac transgenic mice, knockouts, knockins, traditional transgenics, and CRISPR/Cas9 or TALEN genome editing. We also have an extensive line of stem cells and cell culture reagents, as well as custom virus packaging. Our VectorBuilder platform provides a wide variety of molecular engineering services, including PiggyBac-based vectors. Using our innovative online tools, you can design and order custom DNA constructs specific to your experimental needs. Choose from lentiviruses, AAV vectors, shRNA expression vectors, CRISPR/Cas9 vectors, and more!

Bibliography

  1. Friedli M, Trono D. The Developmental Control of Transposable Elements and the Evolution of Higher Species. Annu Rev Cell Dev Biol. 2015 Nov 13;31:429-51.
  2. Muñoz-López M, García-Pérez JL. DNA transposons: nature and applications in genomics. Curr Genomics. 2010 Apr;11(2):115-28. 
  3. Rad R, Rad L, Wang W, Cadinanos J, Vassiliou G, Rice S, Campos LS, Yusa K, Banerjee R, Li MA, de la Rosa J, Strong A, Lu D, Ellis P, Conte N, Yang FT, Liu P, Bradley A. PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice. Science. 2010 Nov 19;330(6007):1104-7.
  4. Yusa K, Zhou L, Li MA, Bradley A, Craig NL. A hyperactive piggyBac transposase for mammalian applications. Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1531-6.

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