Tuned Dynamics

The DNA of all living organisms, the genetic material that holds all the hereditary information of an individual organism, is not the static repository of genes envisaged by early scientists. Although mutations were an accepted part of hereditary theory from the outset as the source of genetic variation, the idea that individual subsets of genetic material could be highly mobile was not well received at the time it was proposed (McClintock, 1947).

In the early part of the twentieth century, geneticists such as Thomas Hunt Morgan and Rollins Emerson had produced detailed genetic maps of Drosophila and Zea mays and had established the structural relationship between genes and chromosomes. In addition to defining their functions, they had shown that genes have an exact location on the chromosome. Thus, the abstract idea of a ‘gene’ had acquired a material identity.

These are the first two paragraphs from my PhD thesis, submitted in Trinity Term of 2004. What continued was a detailed, molecular analysis of the biochemistry of DNA transposition, a process that excises a defined stretch of DNA from one source, and inserts it, mostly at random, into another location.

The bigger picture here is that genomes are dynamic systems. Individual mutations are necessary to generate new functions, but are usually small and provide only limited ability to generate larger scale alterations. Among several other mechanisms, transposons create genomic novelty as a side product: at times, the process goes awry - from the point of view of the transposon - and rather than moving its own genetic sequence, the process can change the location of adjacent sequences, creating insertions and rearrangements that are at a larger scale than a random point mutation.

Whole book chapters and review articles are devoted to the question of how DNA transposition enables evolutionary change. The standard textbook Mobile DNA is now in its third edition, spans 55 chapters, and exceeds 1,300 pages. Mobile genetic elements occur in every organism analysed; they are the origin of introns, drive diversity in our antibody repertoire, and constitute a major burden in the spread of antibiotic resistance.

And, as most actions in biology come hand in hand with a re-action, the same is true for mobile genetic elements. Organisms have evolved suppression mechanisms, ‘immunity’ against transposons, silencing methods and repressor proteins. Unbounded novelty is detrimental, just as too much stasis leads to brittle systems that are not able to withstand changes at different levels.

My part in this long story was contained and comparatively short. Nonetheless, I learned a great deal about the ingenious ways in which transposons can generate genomic diversity - mostly as an ‘inadvertent’ artefact of their mobilisation mechanism. What this means is that evolution has led to a whole range of transposon families that replicate via different mechanisms, each of which can have a different set of genomic consequences and side effects. Variety begets variety, while the countermeasures must be tailored and specific. There was a lot of talk of an ‘arms race’ between transposons and their hosts, a direct and intimate co-evolution at the molecular scale—variation, adaptation, and counter-play—long before any of this would have been visible to a human observer without a molecular toolset.

And as much as the field of DNA transposition or Mobile DNA is a highly specialised field of research, with maybe less than 20 labs worldwide focussed on this area, the lessons of novelty, dynamics, and counter-measures ring true in many other contexts. I would be ill-advised to map too closely the learnings from a molecular mechanism onto how we in society engineer, manage and act as custodians of innovation - but I am inclined to believe that some lessons withstand the shift from the molecular scale to society unblemished: Innovation requires change and adaptability, and a balance between the forces of stasis and movement.

For some this might sound too generic or obvious. I disagree. For me, the key insight is that innovation requires balanced and tuneable disruption. We need systemic challenges in addition to the stability that institutions provide. Managed access to new ideas, curated, sometimes daring, exposure to novelty adjacent to our own core knowledge. Our own creative minds ask for it, and innovative systems require it.