Each summer, who plant in Gill carefully plan our experiments, plant our seed, watch as the seedlings grow up, and wait until the corn plants are ready to cross-pollinate. When they are nearly ready, about six weeks after sowing, we have to walk our rows, looking for the emerging ear shoots so we can cover them with an "ear shoot bag" before the silks emerge. This makes it possible to prevent the ears from being pollinated randomly. We then take pollen from one plant and sprinkle it on the silks of another plant to make new genetic combinations. This is at the core of how geneticists approach problems; we make different combinations of variants to understand how various phenomena are regulated. Nothing I do in the laboratory makes sense except in the light of the genetics I do in the field each year.
Mutants, plants that look or behave in unexpected ways, are key. The concept is easy to understand. If we want to understand how plants work, a good start is to break the genes that determine how they work and see what happens. For instance, if we want to know how a plant decides to make a tassel rather than an ear, we look for a mutant that fails to make the distinction. One set of mutants, called the Tasselseeds, make an ear in place of a tassel. If we can find the DNA sequence for the genes that are broken in these mutants, we can find clues as to how a small group of cells can be instructed to make one structure rather than another. Similarly, a white seedling can tell us about how plants make chlorophyll, the green pigment plants depend on to absorb sunlight and create the energy in all the food we eat. An upside down leaf can tell us how plants determine top and bottom, a plant that grows flat on the ground can tell us how plants sense gravity. And so on. That is why we love mutants. Every one of them provides a clue.
One common source of naturally occurring mutations are transposable elements, or transposons. These are stretches of DNA that can make duplicate copies of themselves. In doing so, they can move from place to place within the genome (the total collection of all the DNA in a living thing). Transposons were discovered many decades ago by Barbara McClintock, a pioneering maize geneticist who received a Nobel Prize for this discovery. She did it by looking at ears of corn and performing the appropriate cross-pollinations, year after year, decade after decade. Nothing fancy or high tech about it. Just patience and an intuitive sense for performing the right experiments and interpreting them correctly. It is remarkable that, even today, the exact same kinds of experiments, involving crossing, looking and thinking are still key to our work. McClintock used to call it having a feeling for the organism.
When McClintock first discovered transposons back in the 1950s, she had no way of knowing how important they are. It turns out that all organisms, from bacteria to fungi and plants and animals are home to vast numbers of these tiny genetic elements. In fact, if you add up all the DNA in all plants, the majority, probably the vast majority, of their DNA is composed of transposons. And it’s not just plants. At least half of our DNA as human beings is composed of transposons as well. As it turns out, much of what we thought was us is really them.
So what are transposons there for? What do they do? We really aren’t sure, but our best guess right now is that they are there because they can be. Essentially, they survive as tiny parasites within our genome because they can out-replicate all of the other genes. In short, they cheat. In some ways, one can think of them as viruses that entered our genomes and never left and, in fact, many of them are relatives of retroviruses such as HIV. They just get passed on to our progeny, generation after generation, making Xerox copies of themselves to survive. We used to think of the genome as the place where all the information is stored, like a hard drive. Now we are beginning to think of the genome as an ecosystem, a place that is inhabited by a vast repertoire of genetic elements, only some of which are “for” making us.
Transposons can cause problems, most of which stem from the fact that they insert at new positions in the genome. If they jump into a gene, they can mutate it, which can be lethal to the host, and in fact transposon insertions are known to cause some human diseases. Sometimes the mutations can turn out to be beneficial and transposons can, in those cases, facilitate evolution, which is one of the reasons many of us are fascinated by them. It is as if our genomes are poised in a dynamic state of disequilibrium, prone to rapid change because of this semi-autonomous part of our genetic code. I know. It sounds like fringe science, or science fiction, but in fact this is very much a standard understanding of the nature of our genomes. Wild, huh?
As useful as they may be in some situations, unrestrained jumping of transposons is not a good thing, since most insertions are deleterious. To deal with this, all higher organisms have an “immune system” whose function is to find transposon sequences and keep them inactive, a process called epigenetic silencing. That is what I’ve been studying at for the past decade or so. Our most significant discovery was a key clue as to the way active transposons are recognized and silenced. Essentially, we found an “antigen” that can trigger silencing of the specific transposon we study. It was the first example of this process found in any organism and it was discovered because of a single cross in the field that gave rise to a single ear of corn that looked unusual. Cross, look, think. Repeat.
As a research scientist, I am motivated by curiosity. I simply want to know how the world works and how we fit into it. For me personally, it really is a question of aesthetics. I find biological truth beautiful, and it is deeply satisfying to reveal that beauty. Fortunately for me, and for you, that process can end up being incredibly useful. As it turns out, for instance, the transposon silencing system we study in maize is related to a vast repertoire of other silencing systems that are responsible for the ordered progression of changes in gene expression in both plants and animals as they develop, the regulation of genes that can lead to cancer, our capacity to fight off disease, and a surprising range of natural variation that we have only recently begun to appreciate. In fact, the strange process of transposon silencing that McClintock first observed in corn decades ago has turned out to help to inform our understanding of nearly every biological phenomenon.
That being said, it should not be denied that basic research can be dangerous. The more we know about the fundamental processes of life, the more we can manipulate them. Because of that, one might make the decision that basic research really is too dangerous, that we just shouldn’t know some things. I suspect that many activists on the Left and the Right might agree with that, and given the range of egregious misuses of technology derived from basic research, they may have a point. Not surprisingly, I disagree. Given the challenges we face, I believe that choosing ignorance over understanding would be a terrible mistake. Imagine, for instance, if no one had been doing basic research on retroviruses before the AIDS epidemic, or if there had been no funding for climate science prior to our understanding that global warming was a threat.
We cannot simply close our eyes and pretend that a superficial understanding of biological phenomena is sufficient. Nor can we constantly try to direct our science funding to the most trendy or seemingly useful applied research agenda, no matter how important it may seem at the moment. Instead, we need to have to courage to look as clearly and honestly and deeply as we can at the world around us.