Since the acceptance of mobile genetic elements as ubiquitous entities across the eukaryotic genome and their detection in prokaryotes, momentum has gathered around this field – as was evident at the 2014 Mobile Genetic Elements and Genome Evolution Keystone Symposium, organised by the Editors-in-Chief of Mobile DNA. In an Opinion article in Mobile DNA leading researchers attending the symposium present their thoughts on where mobile DNA research is going, including Marlene Belfort from the University at Albany, USA. Journal Development Editor for Mobile DNA Sam Rose (@Rosenovich) asked Belfort for her thoughts on the balance between eukaryotic and prokaryotic research in this field, as well as the most exciting recent developments.
What led to your interest in mobile genetic elements?
I was led to mobile genetic elements because of my interest in introns and splicing. Then it turned out that these self-splicing introns were also mobile at the level of the DNA, and so my interest turned there. I have to say that I was trained in bacteriophage lambda and temperate phage, which are in a sense mobile elements, as they integrate into genomes and are excised from genomes. So discovering that the introns I was investigating were mobile led me into a field with which I was quite familiar. I did not intend to study mobile elements after I had left lambda but I stayed with it because I think they’re so profoundly important in sculpting genomes, and so in fashioning what the DNA of an organism really looks like.
What’s the most exciting recent advance in mobile DNA research?
It’s really excited because the very fundamental work that is done in mobile elements is becoming so hugely applied. Haig Kazazian work on line elements, their role in various diseases, and the fact that they have different patterns in cancer (whether that’s causal or consequential) is very profound. Then, at the other end of the spectrum, there is the use of transposons as landmarks in the genome to do high-throughput sequencing and further advance the field. Advances in the field are in part because of this massive ability to sequence these genomes so we can really follow elements and see where they’re going. Now it’s come full circle – the very elements that we can follow are becoming useful in generating the next generation of data.
What are the big questions at the moment?
I think the biggest question that remains is interpreting the activity of line elements in neurons. Ever since Rusty Gage’s discovery some years ago of line element activity in neurons, the question is: do the dynamics we see have a consequence in terms of neuronal function and brain function?
What directions do you see the mobile DNA field going in?
I think that the field will continue to not only provide insights into genome dynamics in healthy populations of all different kinds, but in disease populations. I think an understudied area is the responses of these elements to stresses of various kinds. I think part of the distribution of these elements results from radiations of the elements during times of stress. We know that they’re responsive to stress but we have just scratched the surface. That’s where evolution lies; our responsiveness to stress, our adaptations to stress. I think that the various kinds of mobile introns play a huge role in this.
In terms of where I see the field going, I see the use of transposable elements in various forms of genotyping in medical applications, but also more fundamental insights. For example, insights into the structure of various transpososomes such as line elements – really the structure of the entity that targets the DNA. I think both exploitation of the elements for various practical purposes and more fundamental insights are all in our future.
A large amount of mobile DNA research has been carried out in eukaryotes and less so in prokaryotes. Why do you think this is?
I think that it is easier to get funded for work that has potential applications in human health and so I think the eukaryotic work is really more readily fundable than the bacterial work. It’s a great shame because I think we are where we are because of our profound understanding of what happened in different domains of life. We as scientists are adaptive and so we move our work in the direction of maximum funding, and I think that lies with eukaryotic systems and ultimately mammalian and human systems. Until there is less pressure pushing the science towards translation, there is going to be more emphasis on the eukaryotic than on the bacterial. But I think many, many answers lie in bacteria. CRISPR is a good example of that, a kind of discovery that really would have been missed if there weren’t this tradition of funding fundamental work in the best model organisms possible.